Cerebral microcirculation disorders after recanalization in acute ischemic stroke: A narrative review

Abstract

Acute ischemic stroke, a leading cause of global disability and mortality, faces a critical challenge of cerebral microcirculation disorders despite successful vascular recanalization. This narrative review synthesizes current evidence on the epidemiology, clinical significance, pathogenesis, assessment methods, and therapeutic strategies for post-recanalization microcirculatory dysfunction. Key findings from the literature reveal that microcirculation impairment, driven by hemodynamic instability, neutrophil-platelet interactions, fibrin deposition, endothelial/pericyte dysfunction, blood–brain barrier disruption, and oxidative stress, significantly contributes to futile recanalization and poor prognosis. Advanced imaging modalities, such as dynamic contrast-enhanced magnetic resonance imaging and two-photon microscopy, have emerged as pivotal tools for real-time evaluation of microvascular perfusion and permeability. Pharmacological interventions, including antiplatelet agents, neuroprotective drugs (e.g., butylphthalide), and traditional Chinese medicine (e.g., Danshen Chuanxiongqin), alongside non-pharmacological approaches such as normobaric hyperoxia and hypothermia therapy, demonstrate potential in mitigating microcirculatory injury. Recent clinical trials highlight promising strategies, such as glucagon-like peptide-1 receptor agonists and targeted thromboinflammatory therapies, whereas preclinical studies underscore the role of pericytes in regulating capillary flow and neurovascular coupling. However, challenges persist in translating these findings into clinical practice, necessitating standardized assessment protocols and personalized treatment regimens. This review underscores the imperative for multidisciplinary collaboration and innovative research to optimize cerebral microcirculation recovery and help improve the treatment efficacy of acute ischemic stroke.

Introduction

Acute ischemic stroke (AIS) dominates the global stroke field, with approximately 70%–85% of stroke cases belonging to this category, and it has already become a key cause of death and disability among the global population. According to statistics, about 5.5 million people worldwide die of stroke every year, among which ischemic stroke accounts for a relatively high proportion. Moreover, nearly half of stroke survivors will be left with disabilities, bringing a heavy burden to society and families.[1] Currently, reperfusion therapy is the most effective treatment method for AIS, including mechanical thrombectomy and intravenous thrombolysis.[2] However, even if endovascular treatment can achieve recanalization of large blood vessels, nearly half of the patients still have a poor prognosis.[3] The “futile recanalization” caused by microcirculation disorders is largely to blame.[4,5] In these patients, even though the culprit vessels regain patency, the brain tissue perfusion is unsatisfactory. The recanalization of large blood vessels is not equivalent to the reperfusion of brain tissue, and microcirculation disorders after recanalization can cause further damage to the tissue.[6] Multiple clinical studies have shown that many factors, such as the baseline clinical characteristics of patients, such as advanced age, the presence of underlying diseases such as hypertension or diabetes, the prolonged time from onset to recanalization, a large area of the ischemic penumbra indicated by preoperative imaging, as well as imaging parameters, plasma biomarker levels, and endovascular treatment parameters, are all closely related to the risk of microcirculation disorders.[7,8,9,10,11]

Methods

Literature search strategy

A comprehensive literature search was conducted across multiple databases, including PubMed, Web of Science, Embase, and Cochrane Library, to identify relevant studies published between January 2000 and May 2024. The search terms included combinations of keywords such as “acute ischemic stroke,” “cerebral microcirculation disorders,” “reperfusion injury,” “no-reflow phenomenon,” “vascular recanalization,” and “neurovascular unit.” Boolean operators (AND/OR) were used to refine the search. Additional articles were identified through manual screening of reference lists from retrieved publications. Inclusion criteria encompassed clinical trials, animal studies, mechanistic research, and systematic reviews focusing on post-recanalization microcirculatory dysfunction. Exclusion criteria included non-English articles, case reports, and studies unrelated to cerebral microcirculation or ischemic stroke. The selection process involved two independent reviewers screening titles/abstracts followed by a full-text assessment to ensure relevance and quality. Discrepancies were resolved through consensus.

Clinical Significance

Impact on neurological function recovery

Microcirculation disorders significantly impede cerebral tissue perfusion, confining it to a state of ischemia and hypoxia, and severely disrupting metabolic pathways and functional recovery of nerve cells. Despite successful revascularization of major blood vessels, microcirculatory network dysfunction persists. Nerve cells within the ischemic penumbra experience inadequate blood supply, leading to neurological deficits. These deficits demonstrate limited responsiveness to therapeutic interventions and may progressively worsen, resulting in significant impairment of patients’ quality of life, unfavorable clinical outcomes, and increased risk of disability.[6]

Impact on brain edema and intracranial pressure

Microcirculation disorders initiate a progressive injury mechanism compromising blood–brain barrier integrity. Disruption of endothelial tight junctions leads to abnormal extravasation of plasma components into the cerebral interstitium, resulting in rapid exacerbation of vasogenic edema. The accumulating edema fluid exerts a mass effect on adjacent brain parenchyma and microvasculature, creating a self-perpetuating cycle characterized by increasing intracranial pressure. This pathophysiological cascade significantly elevates the risk of life-threatening complications including cerebral herniation.[12,13]

Impact on infarct volume

Microcirculatory dysfunction restricts blood perfusion, leading to progressive expansion of ischemic infarction in affected brain regions. Clinical investigations have demonstrated a significant correlation between reduced microvascular blood flow velocity and diminished blood volume following revascularization, and subsequent increases in infarct volume. These microcirculatory abnormalities have emerged as critical determinants of poor clinical outcomes in patients.[14,15]

Significance for the evaluation of treatment efficacy and prognosis

Microcirculatory dysfunction severity has emerged as a critical quantitative indicator for evaluating treatment efficacy and prognostic outcomes in AIS patients.[6] Continuous monitoring and comprehensive assessment of microvascular status using advanced imaging techniques enable early detection of pathological changes, allowing for timely adjustments to therapeutic strategies and the development of precision medicine approaches. These monitoring modalities provide objective insights into disease progression, enhancing the ability to optimize clinical management. In addition, molecular biomarkers associated with microcirculatory impairment are being explored as potential prognostic indicators, offering valuable data to improve clinical decision-making frameworks.[16]

Table 1 summarizes the mechanisms of microcirculation disorders after vascular recanalization in AIS, diagnostic methods, treatment strategies, and some ongoing clinical trials. The specific content is as follows.

Table 1.

Summary of mechanisms, diagnostic tools, and therapeutic strategies for post-recanalization cerebral microcirculation disorders in acute ischemic stroke

Category: Core mechanisms	Subcategory: Subtypes	Key details: Key pathways	References
Hemodynamic alterations	Vasoconstriction, blood volume loss, flow velocity reduction	Pial/perforating artery spasm; venular collapse; arteriolar/venular constriction	[17,18]
Cellular-molecular obstruction	Platelet-neutrophil aggregation, fibrin deposition	GPVI-mediated complex formation; thrombin-fibrinogen conversion	[19,20,21,22,23,24,25,26]
Vascular structural dysfunction	Endothelial injury, pericyte dysfunction, microvascular remodeling	Endothelial swelling; pericyte contraction/death; wall thickening/stenosis	[27,28,29,30,31]
Blood-brain barrier disruption	Edema formation, inflammatory infiltration	Endothelial junction disruption; neutrophil/monocyte infiltration	[32,33,34,35]
Energy metabolism disorders	Sodium-potassium pump failure, mitochondrial dysfunction	ATP depletion; oxidative stress-induced mitochondrial damage	[36,37]
Oxidative stress and inflammatory reaction	Oxidative stress damage, activation of inflammatory signal pathways	Nuclear factor-κB and mitogen-activated protein kinase activated	[27,38]
Collateral and reperfusion issues	Poor collateral circulation	Ischemia-reperfusion injury: Oxidative stress; inflammation; hemorrhagic transformation and brain edema	[39,40,41]
	Ischemia-reperfusion injury
Diagnostic tools	Method and application	Key parameters	References
Clinical indicators	mTICI grading: Assess recanalization degree	mTICI ≥2b with hypoperfusion >40%	[42]
	mRS score: Evaluate functional outcomes	90-day mRS ≥2 indicates disability	[43]
Imaging techniques	CTP: Quantify CBF, MTT	Prolonged MTT reflects microvascular obstruction	[44]
	LSCI: Real-time microvascular flow velocity/perfusion monitoring	Speckle contrast correlated with blood flow	[45,46]
	Two-photon microscopy: High-resolution visualization of microvessel structure/cellular interactions	Capillary diameter, blood cell-endothelial adhesion	[47]
	DCE-MRI: Assess blood-brain barrier permeability	Ktrans, Vp, Vl parameters	[48]
	ASL/BOLD fMRI: Assess the reserve function of cerebral microcirculation	ASL: CBF	[49,50]
		BOLD: Neuronal activity and CVR
	PET-CT: Reflect the metabolic function of tissues or organs	Cerebral blood flow and cerebral oxygen consumption metabolic rate	[51]
	Doppler ultrasonography technology	Blood flow velocity	[52,53]
		Spectrum morphology
		PI
		RI
Laboratory methods
Histological examination	HE staining: Show the structure and changes of the basement membrane of microvessels	The morphology, structure, and distribution of microvessels	[54]
Special staining	PAS staining: Show the structure and changes of the basement membrane of microvessels	Carbohydrate substances	[55,56]
	Masson staining: Determine the degree of fibrosis and its relationship with microvessels	Collagen fibers
Immunohistochemical staining	Immunohistochemistry: Detect endothelial markers (CD31, CD34) and angiogenic factors (VEGF, NOS)	Microvessel density, protein expression levels	[57,58,59]
Electron microscopy examination	Ultrastructural analysis of endothelial tight junctions and basement membrane	The microvessel density, the number of microvessels	[60,61]
	Laser scanning confocal microscopy examination: Discovering morphological changes such as abnormal branches and tortuosity of microvessels	Three-dimensional spatial structure and distribution of microvessels	[62,63]
Therapeutic strategies	Intervention and mechanism	Key agents/techniques	References
Pharmacological therapy	Thrombolytics: Dissolve microthrombi	Urokinase, alteplase	[64]
	Antiplatelet agents: Inhibit platelet aggregation	Ticagrelor, aspirin, troxerutin, vinpocetine tablets	[64,65,66]
	Neuroprotectants: Reduce endothelial injury and oxidative stress	Butylphthalide, flunarizine	[64,67,68]
	Traditional Chinese medicine treatment: Promoting blood circulation to remove blood stasis and dredging collaterals	Danshen chuanxiongqin Injection, naoxintong capsule, Ginkgo Biloba leaves tablets	[69,70]
	Vasodilators: Improve microvascular perfusion	Alprostadil, nimodipine	[71,72]
Nonpharmacological therapy	NBO: Increase oxygen delivery and reduce edema	Inhalation of high-concentration oxygen	[73,74,75]
	Hypothermia therapy: Reduce metabolic demand and inflammation	Mild hypothermia (32°C–35°C)	[76,77]
	Ozone autohemotherapy: Antioxidant effects	Inhalation of ozone	[78]
Endovascular therapy	Endovascular devices: Mechanical thrombectomy combined with real-time imaging guidance	Stent retrievers, ultrasound-assisted catheters	[2,3,7,8,9,10,11,79,80]
Clinical trials	Treatment targets	Current status and key trials	References
Y-6 sublingual tablets	Improve microcirculation disorders after reperfusion	Phase II trials: NCT05836753 (ESPRIT)	[81]
Targeted thromboinflammatory therapy (ND886 drug combined with reperfusion therapy)	Improve microcirculation disorders after reperfusion	Phase IIa trials (e.g., ND886)	[82]
Intra-arterial tenecteplase after endovascular thrombectomy	Improve microcirculation disorders after reperfusion	Phase III trialsNCT05684172 (Attention IA)	[83]

AIS: Acute ischemic stroke, BBB: Blood-brain barrier, mTICI: Modified thrombolysis in cerebral infarction, mRS: Modified Rankin Scale, ASL: Arterial spin labeling, BOLD fMRI: Blood oxygenation level-dependent functional magnetic resonance imaging, CTP: CT perfusion imaging, CBF: Cerebral blood flow, MTT: Mean transit time, LSCI: Laser speckle contrast imaging, DCE-MRI: Dynamic contrast-enhanced magnetic resonance imaging, NBO: Normobaric hyperoxia, HE staining: Hematoxylin-eosin staining, PAS staining: Periodic acid-Schiff reaction, CVR: Cerebrovascular reactivity, PI: Pulsatility index, RI: Resistance index, VEGF: Vascular endothelial growth factor, NOS: Nitric oxide synthase

The Mechanisms of Microcirculation Disorders after Recanalization

Hemodynamic alterations

Postrecanalization microcirculatory evaluation in AIS penumbra demonstrates:[17,18]

• Vasoconstriction of pial/perforating arteries with abrupt pial flow reduction

• Compensatory but insufficient perforating artery flow recovery

• Venular/pial venous collapse causing blood volume loss

• Arteriolar/venular constriction reducing flow velocity/volume

• Capillary narrowing with depressed flow dynamics.

Microvascular pathophysiology

Cellular-molecular obstruction

• Platelet-neutrophil aggregation: Glycoprotein VI (GPVI)-mediated thromboinflammatory signaling promotes platelet-neutrophil complex formation. Neutrophil β2 integrins mediate capillary plugging, exacerbating injury[19,20,21,22,23]

• Fibrin deposition: Thrombin converts fibrinogen to fibrin, forming microthrombi that impede flow. Fibrin–integrin interactions propagate obstruction and inflammation.[24,25,26]

Structural dysfunction

• Endothelial injury: Ischemia-reperfusion induces endothelial swelling, junctional disruption, and permeability increase. Dysfunctional endothelium reduces nitric oxide while upregulating endothelin-1, causing vasoconstriction[27,28]

• Pericyte dysfunction: Calcium overload/excitotoxicity/oxidative stress triggers pericyte contraction/death, narrowing capillary lumens and impairing perfusion[29,30]

• Microvascular remodeling: Chronic processes (e.g., hypertension/diabetes) drive wall thickening/lumen stenosis, increasing microcirculatory resistance.[31]

Blood–brain Barrier Disruption

Brain edema formation

Domestic studies have found that after vascular recanalization, the blood–brain barrier is disrupted, and cerebrospinal fluid flows into the brain tissue interstitium, resulting in brain edema. The swelling of cells and perivascular tissues can compress microvessels and impair microcirculation perfusion. Foreign studies have also confirmed the key role of blood–brain barrier disruption in microcirculation disorders. Brain edema can lead to an increase in intracranial pressure, further affecting the blood perfusion of brain tissue and forming a vicious cycle.[32,33]

Inflammatory reaction and immune cell infiltration

Studies both at home and abroad have shown that after the disruption of the blood–brain barrier, inflammatory cells such as neutrophils and monocytes can infiltrate brain tissue and release inflammatory mediators, such as tumor necrosis factor-α and interleukin-1 β, aggravating tissue damage and microcirculation disorders. Meanwhile, the inflammatory reaction can also induce endothelial cells to express adhesion molecules, promoting the adhesion and aggregation of platelets and white blood cells.[34,35]

Energy Metabolism Disorders

Failure of the cell sodium-potassium pump function

Studies at home and abroad have found that the interruption of blood flow leads to an insufficient supply of energy substances, causing energy failure of the cell sodium-potassium pump and electrolyte disorders, making endothelial cells and astrocytes swell and then compress microvessels, affecting microcirculation perfusion.[36]

Mitochondrial dysfunction

Foreign studies have shown that ischemia-reperfusion can lead to mitochondrial damage, affecting the energy metabolism of cells, reducing the generation of intracellular ATP and resulting in insufficient energy supply, leading to dysfunction of the contractile function of microvascular smooth muscle cells and affecting the hemodynamics of the microcirculation. Meanwhile, mitochondrial damage can also trigger oxidative stress reactions, further aggravating cell damage and microcirculation disorders.[37]

Oxidative Stress and Inflammatory Reaction

Oxidative stress damage

Studies both at home and abroad have shown that during the ischemia-reperfusion process, a large number of reactive oxygen free radicals, such as superoxide anions and hydroxyl radicals, are generated, which can lead to lipid peroxidation of cells, oxidative modification of proteins, and DNA damage, destroying the structure and function of vascular endothelial cells, pericytes, etc., and aggravating microcirculation disorders. Meanwhile, oxidative stress can also activate inflammatory signal pathways and promote the occurrence of inflammatory reactions.[27,38]

Activation of inflammatory signal pathways

Domestic studies have found that during the process of microcirculation disorders after recanalization, multiple inflammatory signal pathways, such as nuclear factor-kappa B and mitogen-activated protein kinase, are activated, promoting the expression and release of inflammatory cytokines, exacerbating the inflammatory reaction, and further damaging microvessels and brain tissue.[54]

No-reflow Phenomenon

The no-reflow phenomenon refers to the situation where, despite the successful opening of blood vessels, there is still a lack of tissue reperfusion. This may be secondary to the capillary constriction caused by the destruction of pericytes in the ischemic area, which may then damage the perfusion of the capillary bed and lead to microcirculation disorders.[11]

Poor Collateral Circulation

Poor collateral circulation is associated with successful reperfusion by endovascular treatment and a good outcome.[73] If the arterial collateral circulation is poor, the occluded blood vessel will not be able to obtain sufficient blood supply, resulting in the expansion of the ischemic penumbra and an increase in the final infarct volume.[39]

Ischemia-reperfusion Injury

Restoring blood perfusion not only fails to reverse neurological function impairment but also aggravates the functional, metabolic disorders, and morphological and structural damage of cells in tissues and organs, which is called ischemia-reperfusion injury. Disrupting the blood–brain barrier is an important pathological process, which can further lead to changes such as hemorrhagic transformation and brain edema.[40,41] The research on these mechanisms helps to deeply understand the complexity of microcirculation disorders after vascular recanalization and provides a scientific basis for the development of new treatment strategies.

The above content is a summary of the mechanism of cerebral microcirculation disorders after recanalization in AIS, and Figure 1 vividly illustrates this specific mechanism.

Figure 1.

Mechanism of cerebral microcirculation disorders after recanalization in acute ischemic stroke. The specific mechanisms mainly include: hemodynamic changes; adhesion of blood components causing blockage (interaction between platelets and neutrophils, and fibrin deposition); abnormal vascular structure and function (endothelial cell damage and pericyte dysfunction); microvascular remodeling and stenosis; blood-brain barrier damage; energy metabolism disorders (cell sodium-potassium pump failure and mitochondrial dysfunction); oxidative stress

Assessment Methods for Microcirculation Disorders after Recanalization

Neurointerventional indicators

The Modified Thrombolysis in Cerebral Infarction (mTICI) grading is used to assess the recanalization degree of the culprit occluded vessels. The definition of no-reflow includes that the mTICI of the culprit vessel is ≥ 2b, and the hypoperfused area of the affected brain tissue relative to the healthy side exceeds 40%. This reflects that from the perspective of tissue perfusion after vascular recanalization, there is still a large area of brain tissue that has not received a good blood supply, suggesting that there may be microcirculation disorders caused by no-reflow, which then affects the perfusion of brain tissue.[42] The modified Rankin Scale (mRS) score is an indicator for assessing the degree of disability or functional recovery of patients. A 90-day mRS score ≥ 2 indicates that the patient still has a certain degree of disability or functional impairment 90 days after vascular recanalization treatment, which may be related to brain tissue damage and insufficient perfusion caused by no-reflow.[43] However, this indicator is also just a reference, because there are numerous reasons for the poor functional recovery of patients at 90 days, and the diagnosis of no-reflow cannot be made solely based on this.

Neuroimaging assessment

Mean transit time

Mean transit time (MTT) refers to the time from the start of contrast agent injection to when the time–density curve drops to half of the maximum enhancement value. It mainly reflects the time for the contrast agent to pass through capillaries. In perfusion imaging, a prolonged MTT usually indicates poor tissue microcirculation, because the contrast agent stays in the microcirculation for a longer time, suggesting that the blood flow velocity slows down or the vascular resistance increases, resulting in a prolonged time for blood to pass through the capillary network.[46] For example, in the brain, if the MTT in a certain area is significantly higher than that in the normal area, it suggests that there may be microcirculation disorders in this part, such as insufficient perfusion of local brain tissue caused by ischemic cerebrovascular diseases.[44] Doctors can further judge the condition and formulate treatment plans based on this combined with other examination results.

Laser speckle contrast imaging

When the target is irradiated by a laser beam, the reflected laser forms a random interference image, that is, a laser speckle pattern. The movement of red blood cells in the measured object will cause fluctuations in the laser speckle pattern. The speed of speckle changes is quantified by speckle contrast, and the contrast is related to blood flow, so that the blood flow of living tissues can be monitored.[45] It can monitor blood flow velocity and perfusion volume in real time and dynamically, and then accurately assess the structure and function of blood vessels. It can be used to study changes in microcirculation during various disease processes, such as observing the blood perfusion of the microcirculation in the lesion area in real time in diseases such as stroke and myocardial ischemia, providing an important reference for the early diagnosis and treatment of diseases.[46]

Two-photon microscopy

Based on the principle of two-photon excitation fluorescence, high-energy near-infrared laser pulses are used to excite fluorescent molecules to emit fluorescent signals, enabling high-resolution imaging of the internal microstructure and cellular activities of tissues. In microcirculation research, it can clearly observe the morphology, diameter, blood flow velocity of microvessels, and the interaction between blood cells and vascular endothelial cells. It can be used to study changes in the structure and function of microcirculation under normal and pathological conditions, for example, observing the angiogenesis in ischemic tissues, understanding the distribution of cerebral blood vessels and the characteristics of blood flow perfusion; it can also be used to study microcirculation disorders caused by chronic diseases such as diabetes, hypertension, and cerebral ischemia, providing intuitive morphological evidence for the research on the pathogenesis of diseases.[47]

Dynamic contrast-enhanced magnetic resonance imaging

By injecting a contrast agent intravenously, magnetic resonance imaging (MRI) technology is used to continuously and rapidly collect information on the distribution and dynamic changes of the contrast agent within tissues. When the blood–brain barrier is damaged, the contrast agent gadolinium chelate will leak from the blood vessels into the brain tissue, resulting in an increase in the T1-weighted signal intensity of the brain tissue. Then, with the help of pharmacokinetic models, such as the commonly used Patlak model, parameters such as the blood–brain barrier transfer constant (Ktrans or Ki), intravoxel plasma volume (Vp), and permeable volume (Vl) are calculated to assess the leakage amount and leakage rate of the blood–brain barrier, and then reflect the severity of cerebral microcirculation disorders. 50 It is widely used in the diagnosis and research of brain diseases. In cerebrovascular diseases, it can be used to study blood–brain barrier damage and microcirculation disorders caused by ischemic cerebrovascular diseases and to assess the treatment effect.[48]

Functional magnetic resonance imaging

Arterial spin labeling

It is a noninvasive cerebral perfusion MRI method that uses water molecules in blood as an endogenous contrast agent. By radiofrequency pulse labeling of water molecules in arterial blood to change their magnetization vectors, and then detecting the signals of the labeled water molecules in brain tissue, information on cerebral blood flow (CBF) is obtained, which in turn reflects the perfusion status of cerebral microcirculation. It does not require an injection of a contrast agent, is simple and safe to operate, and can be used for the diagnosis of cerebral ischemic lesions, condition assessment, and monitoring of treatment effects. In patients with acute cerebral infarction, arterial spin labeling can early detect the reduction in CBF perfusion in the ischemic area, providing an important basis for clinical treatment.[49]

Blood oxygenation level-dependent functional magnetic resonance imaging

Based on the principle that changes in the oxygen content of brain tissue will cause changes in the magnetic resonance signal intensity. When the neuronal activity in a certain area of the brain increases, the local CBF increases, while the oxygen uptake increases relatively less, resulting in an increase in the local oxygen content of blood, which enhances the magnetic resonance signal in this area. By detecting such signal changes, the neuronal activity and cerebrovascular reactivity (CVR) are reflected, and the function of cerebral microcirculation is indirectly assessed. It can assess the reserve function of cerebral microcirculation by detecting CVR, which is of great significance for predicting the risk of cerebrovascular diseases, formulating preventive strategies, and assessing treatment effects.[50]

Positron emission tomography-computed tomography

It combines positron emission tomography (PET) technology with computed tomography (CT) technology. After the PET radiopharmaceutical is injected into the human body, it participates in the physiological metabolic process of the human body, accumulates in specific tissues or organs, and emits positrons. The positrons annihilate with electrons in the surrounding tissues, generating a pair of gamma photons. The PET detector can detect these photon signals, and images are reconstructed by a computer to reflect the metabolic function of tissues or organs. Meanwhile, CT scanning can provide accurate anatomical structure information. After the two are fused, precise positioning of the lesion site and functional and metabolic assessment can be achieved. In the study of cerebral microcirculation, CBF, and cerebral oxygen consumption metabolic rate can be quantified through specific radiopharmaceuticals. It is regarded as the gold standard for quantifying CBF and cerebral oxygen consumption metabolic rate, and is of great value for the early diagnosis, condition assessment, and treatment effect monitoring of brain diseases. However, due to its high cost and the radioactivity of the used radiopharmaceuticals, its large-scale clinical application is limited.[51]

Doppler ultrasonography technology

It assesses the microcirculation function by detecting the hemodynamic parameters of the main arteries on the intracranial cerebral arterial circle through specific acoustic windows. It is a noninvasive examination method but has certain limitations.

Blood flow velocity

Abnormal increases or decreases in the blood flow velocity of the main intracranial arteries such as the middle cerebral artery, anterior cerebral artery, and posterior cerebral artery may suggest the presence of stenosis, spasm, or insufficient blood supply in the corresponding vessels, which in turn reflects cerebral microcirculation disorders. For example, when the blood flow velocity of the middle cerebral artery is significantly higher than the normal range, it may be due to the stenosis of this artery, resulting in compensatory acceleration of local blood flow and affecting the normal perfusion of the microcirculation.[52,53]

Spectrum morphology

The normal spectrum morphology is a right-angled triangle, with a steep ascending branch in the systolic phase and a slow descending branch in the diastolic phase. If the spectrum morphology is abnormal, such as spectrum broadening or rounding, it may indicate hemodynamic changes related to reduced vascular elasticity, vascular stenosis, or increased microcirculation resistance, which can indirectly reflect cerebral microcirculation disorders.

Pulsatility index and resistance index

Pulsatility index (PI) and resistance index (RI) are indicators that reflect the resistance state of cerebral blood vessels. The calculation formula of PI is (peak systolic velocity-end-diastolic velocity)/mean velocity, and the calculation formula of RI is (peak systolic velocity-end-diastolic velocity)/peak systolic velocity. An increase in the values of PI and RI often suggests an increase in the resistance of cerebral blood vessels, which may be caused by microcirculation disorders resulting in vasospasm, stenosis of small vessels, or reduced elasticity of the vessel wall.[52,53]

Neuropathological Methods

These methods can directly reflect the microcirculation function by observing the pathological manifestations of specimens. However, due to their invasiveness, their application in clinical practice is limited, and they are often used in research on animal models. The specific methods are as follows.

Histological examination

Hematoxylin and eosin staining

It is one of the most commonly used histological staining methods. Through hematoxylin and eosin staining, the morphology, structure, and distribution of microvessels in brain tissue can be observed. For example, the microvessels in normal brain tissue should have an intact vessel wall structure with a relatively uniform lumen size. In the presence of cerebral microcirculation disorders, manifestations such as thickening of the microvessel wall, stenosis or deformation of the lumen, and a decrease in microvessel density (MVD) may occur.[54]

Special staining

Periodic acid-Schiff reaction (periodic acid-Schiff staining)

It is mainly used to display carbohydrate substances in tissues and can clearly show the structure and changes of the basement membrane of microvessels. In the case of cerebral microcirculation disorders, changes such as thickening and unevenness may occur in the basement membrane of microvessels, and periodic acid-Schiff (PAS) staining is helpful for observing and evaluating these lesions.[55]

Masson staining

It is commonly used to observe collagen fibers in tissues. Through Masson staining, the proliferation of collagen fibers around microvessels can be understood. After cerebral microcirculation disorders, local tissues may show fibrotic changes, and Masson staining can help determine the degree of fibrosis and its relationship with microvessels.[56]

Immunohistochemical staining

Labeling microvessel endothelial cells

Using antibodies against specific markers of microvessel endothelial cells, such as CD31 and CD34, for immunohistochemical staining can specifically label the microvessel endothelial cells in brain tissue, enabling more accurate observation of the density, morphology, and distribution of microvessels. For example, in diseases causing microcirculation disorders such as cerebral ischemia, the number and morphology of microvessel endothelial cells may change, and immunohistochemical staining can be used for quantitative and qualitative analysis of these changes.[57,58]

Detecting the expression of related proteins

By using immunohistochemical staining to detect the expression of proteins related to the regulation of cerebral microcirculation, such as vascular endothelial growth factor (VEGF) and nitric oxide synthase (NOS). VEGF plays an important role in angiogenesis and the regulation of vascular permeability, and changes in its expression level may be related to the compensation or damage of cerebral microcirculation; NOS is involved in regulating the vasodilation function, and its abnormal expression may affect the hemodynamics of cerebral microcirculation. Therefore, detecting the expression of these proteins is helpful for in-depth understanding of the pathological mechanism of cerebral microcirculation disorders.[59]

Electron microscopy examination

Ultrastructural observation

Electron microscopy can provide a higher resolution than light microscopy and can be used to observe the ultrastructural details of microvessels in brain tissue, such as the tight junctions of endothelial cells, pinocytotic vesicles, and the layered structure of the basement membrane. In the case of cerebral microcirculation disorders, the tight junctions of endothelial cells may be damaged, leading to an increase in vascular permeability; the number and function of pinocytotic vesicles may change, affecting substance exchange, etc. These changes in ultrastructure are of great significance for in-depth understanding of the occurrence mechanism of microcirculation disorders.[60]

The Relationship between Microvessels and Surrounding Tissues

Electron microscopy can also observe the mutual relationship between microvessels and surrounding tissue cells such as neurons and glial cells. For example, it can be observed whether the synaptic connections between neurons and microvessels are normal and whether glial cells exert compression or support effects on microvessels. Changes in these relationships may affect the function of cerebral microcirculation and the metabolism of brain tissue.[61]

Morphometric analysis

Microvessel density determination

By counting and measuring microvessels on tissue sections and calculating the MVD, the number of microvessels in brain tissue can be quantitatively evaluated. Generally, after immunohistochemical labeling of microvessel endothelial cells, multiple fields of view are selected under a microscope for counting, and the MVD value is calculated according to a certain formula. In the case of cerebral microcirculation disorders, the MVD value may decrease, reflecting a reduction in the number of microvessels and thus suggesting insufficient blood perfusion of local brain tissue.

Vascular diameter measurement

Measuring the diameter size of microvessels to understand the degree of dilation or stenosis of the vessels. Image analysis software can be used to measure the images of microvessels in tissue sections to obtain parameters such as the average value, maximum value, and minimum value of the diameter. Changes in the diameter will directly affect the blood flow velocity and blood flow volume of cerebral microcirculation. For example, in cases of vasospasm or arteriosclerosis, the diameter of microvessels will narrow, leading to an increase in blood flow resistance and affecting the perfusion of brain tissue.

Laser scanning confocal microscopy examination

Three-dimensional reconstruction and observation

Laser scanning confocal microscopy can perform multilayer scanning on brain tissue sections and conduct three-dimensional reconstruction through computer software, enabling a more intuitive observation of the three-dimensional spatial structure and distribution of microvessels. This method can provide more comprehensive information and is helpful for discovering morphological changes such as abnormal branches and tortuosity of microvessels, as well as the spatial relationship between microvessels and surrounding tissues.[62]

Fluorescence labeling and functional studies

By using fluorescently labeled tracers or antibodies in combination with laser scanning confocal microscopy, the functions of microvessels such as permeability and substance transport can be studied. For example, after injecting fluorescently labeled macromolecular substances such as albumin, the change in the permeability of microvessels can be evaluated by observing their distribution inside and outside the microvessels; or by using fluorescently labeled calcium ion indicators, the change in the calcium ion concentration in microvessel endothelial cells can be observed to understand the vasomotor function state of the vessels.[63]

These assessment methods provide important tools and means for the diagnosis and treatment of cerebral microcirculation disorders after vascular recanalization.

Treatment Strategies for Microcirculation Disorders

The treatment strategies for cerebral microcirculation disorders after vascular recanalization mainly include two categories: Pharmacological treatment and nonpharmacological treatment.

Pharmacological Treatment Methods

Thrombolytic therapy

Thrombolytic therapy aims to dissolve the formed microthrombi, achieve reperfusion before irreversible damage occurs, and block the development of the ischemic cascade. Commonly used thrombolytic drugs include urokinase and recombinant tissue plasminogen activator.[64]

Anticoagulant therapy

Anticoagulant therapy can prevent the further development of microthrombi. Commonly used drugs include heparin derivatives and direct thrombin inhibitors, such as hirudin and argatroban.[64]

Fibrinolytic therapy

Fibrinolytic drugs can reduce the level of fibrinogen, decrease the risk of thrombosis, accelerate blood flow velocity, and improve microcirculation.[64]

Antiplatelet therapy

Antiplatelet drugs inhibit platelet activity and aggregation through different pathways, reduce the adhesion of platelets to the vessel wall, and prevent the formation of new microthrombi.[64]

Neuroprotective drugs

Ideal neuroprotective agents should have the characteristics of few adverse reactions and be easy to apply in the pre-hospital environment. Non-pharmacological neuroprotective therapies aim to change the apoptotic cascade of nerve cells in the ischemic penumbra area. The following are some specific neuroprotective drugs, including traditional Chinese medicine treatment and Western medicine treatment.[64]

Traditional Chinese medicine treatment

Danshen chuanxiongqin injection

It has the effects of promoting blood circulation to remove blood stasis and dredging collaterals. It can dilate blood vessels, reduce blood viscosity, improve cerebral microcirculation, and increase blood supply and oxygen supply.[69,70]

Naoxintong capsule

It has the effects of invigorating qi and promoting blood circulation, removing blood stasis, and dredging collaterals. It can improve cerebral blood circulation, increase blood supply and oxygen supply, relieve symptoms such as headache, dizziness, and tinnitus, and reduce the incidence of cardiovascular and cerebrovascular diseases.[69,70]

Ginkgo biloba leaves tablets

Extracted from ginkgo leaves, it can promote blood circulation to remove blood stasis and dredge collaterals, dilate blood vessels, lower blood pressure, and improve microcirculation.[69,70]

Western medicine treatment

Flunarizine

It is a selective calcium antagonist. By preventing calcium ions from entering cells, it relaxes vascular smooth muscle, dilates blood vessels, improves cerebral blood circulation, and can penetrate the blood–brain barrier to regulate cerebral microcirculation.[67]

Butylphthalide

It is a synthetic racemic n-butylphthalide and a new type of drug for improving microcirculation and blood flow in the cerebral ischemic area. It can improve microcirculation and blood flow in the cerebral ischemic area, reduce neurological function damage, and has the effects of anti-cerebral thrombosis and anti-platelet aggregation.[68]

Troxerutin

It is a semi-synthetic water-soluble flavonoid compound prepared by hydroxyethylation of rutin. It has the effects of inhibiting the aggregation of red blood cells and platelets, preventing thrombosis, increasing the oxygen content in blood, improving microcirculation, promoting the formation of new blood vessels to enhance collateral circulation, and protecting vascular endothelial cells.[65]

Vinpocetine tablets

It can inhibit platelet aggregation, reduce the increase in pathological blood viscosity, increase the deformability of red blood cells, inhibit the uptake of adenosine by red blood cells, promote oxygen transport in tissues by reducing the oxygen affinity of red blood cells, selectively increase CBF, increase the percentage of cerebral supply of cardiac output, and reduce cerebrovascular resistance without affecting the parameters of the systemic circulation. It can promote the blood supply to the damaged (non-necrotic) hypoperfused ischemic areas.[66]

Alprostadil injection

It is a vasodilator that can improve microcirculation and has a neuroprotective effect. It can be used to treat cerebrovascular diseases.[71]

Nimodipine injection

It is a calcium antagonist that can improve cerebral vasospasm, increase CBF, and has a neuroprotective effect.[72]

Non-pharmacological Treatment Methods

Promote the effective establishment of collateral circulation

Poor collateral circulation will lead to the rapid progression of the hypoperfused volume and the expansion of the infarct core. Therefore, promoting the establishment and maintenance of collateral circulation has become an important treatment strategy.[73]

Normobaric hyperoxia therapy

Normobaric hyperoxia (NBO) therapy aims to reduce the growth of the infarct core and protect the penumbra. At present, phase II clinical trials have confirmed its safety and feasibility. NBO therapy is a treatment method that allows patients to inhale high-concentration oxygen through specific devices under normal pressure to improve the body’s hypoxic state. It has the following effects in improving cerebral microcirculation: Improving cerebral hypoxia; dilating cerebral blood vessels; reducing blood viscosity; promoting the establishment of collateral circulation; reducing brain edema, etc.[74,75]

Hypothermia therapy

Hypothermia therapy improves cerebral microcirculation disorders mainly through the following mechanisms: Reducing the metabolic rate; reducing brain edema; regulating the tension of cerebral blood vessels; inhibiting vasospasm; reducing the inflammatory reaction; protecting vascular endothelial cells; inhibiting apoptosis, etc.[76,77]

Clinically commonly used hypothermia treatment methods include mild hypothermia treatment. Generally, sedative drugs with inhibitory effects on the central nervous system are used to make patients enter a sleep state, and then physical cooling methods, such as ice caps and cooling blankets, are used to control the patient’s body temperature in a mild hypothermia state, usually around 32°C–35°C, to achieve the treatment purposes of improving cerebral microcirculation and protecting brain tissue.[77]

Ozone autohemotherapy

The trace amounts of lipid oxidation products generated by the mixture of ozone and blood can upregulate antioxidant enzymes, improve the aggregation mode of platelets in blood, prevent thrombosis, promote the oxidation and metabolism of fatty substances such as plaques on the vessel wall, increase vascular elasticity. This therapy has a positive impact on platelet aggregation, cell remodeling, organization of cytoskeletal elements, and mitochondrial structure.[78]

These treatment strategies and methods provide multiple treatment options for cerebral microcirculation disorders after vascular recanalization, aiming to improve microcirculation disorders, reduce brain damage, and improve the prognosis of patients.

Endovascular Therapy

Impact of current techniques on microcirculation

Mechanical thrombectomy has become the standard treatment for acute large-vessel occlusion ischemic stroke. Novel thrombectomy devices (e.g., stent retrievers) have significantly improved large-vessel recanalization rates and reduced disability/mortality through optimized radial force and deliverability.[2] However, clinical data indicate that despite achieving recanalization in > 80% of patients, fewer than 50% achieve favorable outcomes at 90 days,[3] highlighting insufficient microcirculatory reperfusion as a critical prognostic determinant.[7,8,9,10,11] Post-thrombectomy microvascular thromboembolism, endothelial injury, and hemodynamic derangements frequently lead to “no-reflow” or “slow-reflow” phenomena.[11]

Controversies and limitations of adjunctive pharmacotherapy

Intra-arterial thrombolytics (e.g., alteplase) as bridging therapy for mechanical thrombectomy theoretically dissolve distal microthrombi and improve microcirculation.[79] The CHOICE trial suggested that postprocedural intra-arterial alteplase may enhance 90-day functional independence but increases hemorrhage risk.[80] However, guidelines remain inconsistent regarding drug selection, dosing, and timing. Antiplatelet agents (e.g., ticagrelor) and anticoagulants are widely used for thromboprophylaxis, yet the evidence for microcirculatory improvement remains limited.[84] Vasodilators (e.g., alprostadil) may alleviate microvascular spasms but show variable efficacy.[71]

Gaps and challenges in microcirculation-targeted therapies

The pathophysiology of microcirculatory dysfunction involves three core mechanisms: (1) platelet-neutrophil complex-mediated capillary obstruction;[22] (2) fibrin deposition leading to microthrombus formation;[25] (3) endothelial cell swelling and augmented vascular permeability.[28] Despite these well-defined mechanisms, contemporary therapeutic strategies remain primarily focused on achieving large-vessel recanalization, with limited targeted microcirculatory interventions. For instance, mechanical thrombectomy often fails to effectively remove distal microthrombi, while pharmacological approaches lack specificity and safety validation.[4] In addition, real-time microcirculatory monitoring modalities (e.g., orthogonal polarization spectral imaging [OPSI]) are underutilized in clinical practice, thereby limiting adaptive treatment strategies.

Future research directions

To overcome current limitations, neurointerventional research must prioritize the following areas.

Development of Hybrid Devices

Investigate composite devices integrating thrombectomy with microcirculation-protective capabilities, such as ultrasound-assisted thrombolysis catheters or locally drug-eluting thrombectomy systems.

Personalized Combination Therapies

Design “thrombectomy + pharmacotherapy” protocols tailored to individual microvascular profiles (e.g., blood flow velocity, vascular permeability), including targeted inhibition of platelet-neutrophil interactions.

Integrated Monitoring-intervention Systems

Incorporate real-time microvascular flow parameters (e.g., flow index, perfusion density) into treatment algorithms to dynamically adjust vasoactive drug dosages and interventional strategies.

Biomarker-driven Precision Medicine

Evaluate molecular markers (e.g., fibrinogen degradation products, endothelin-1) for predicting microcirculatory injury and guiding precision therapies.

Latest Research Progress

According to the latest research progress, the treatment strategies for cerebral microcirculation disorders have the following progress in clinical research and basic research.

Clinical Research Progress

Pharmacological treatment

Antidiabetic drugs

Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase 4 inhibitors are considered to be able to improve cerebral microvascular function and protect nerve cells.[85]

Semaglutide

Clinical studies have found that semaglutide can significantly reduce the risk of non-fatal stroke, probably by exerting its effects through anti-atherosclerosis and improving microcirculation.[86]

Sodium-glucose cotransporter 2 inhibitors

Animal experiments have shown that these drugs can improve cognitive dysfunction in T2DM mice and have the effects of reducing oxidative stress, and neuroinflammation, and improving the plasticity of nerve cells and the mitochondrial brain pathway.[87]

Receptor for advanced glycation end products inhibitors

They can improve microvascular function by improving oxidative stress and inflammation.[88]

Ongoing Clinical Trials for Cerebral Microcirculation Disorders after Recanalization

Phase IIa clinical trial of Y-6 sublingual tablets for treating microcirculation disorders after reperfusion therapy for AIS with large vessel occlusion

This study aims to improve microcirculation disorders after reperfusion therapy for large vessel occlusion through Y-6 sublingual tablets, thereby reducing the proportion of futile recanalization.[81]

Multicenter, randomized, double-blind, placebo-parallel-controlled, Phase IIa clinical trial (ESPRIT Study) of ND886 drug combined with reperfusion therapy for patients with acute large vessel occlusive ischemic stroke

Based on the results of basic research, this study aims to provide more evidence-based medical evidence for the clinical translation of targeted thromboinflammatory treatment for microcirculation disorders after recanalization.[82]

Study on intra-arterial tenecteplase after endovascular thrombectomy for posterior circulation stroke (ATTENTION IA, NCT05684172)

This study adopted a prospective, multicenter, open-label, endpoint-blinded, randomized controlled trial (RCT) design and was conducted in 31 stroke centers in China. It studied the effect of intra-arterial tenecteplase after successful recanalization by endovascular thrombectomy in patients with posterior circulation AIS caused by proximal large or medium intracranial vessel occlusion. The study conclusion showed that in patients with posterior circulation AIS caused by proximal large or medium intracranial vessel occlusion, intra-arterial tenecteplase treatment after endovascular treatment did not provide additional benefits and might increase the risk of symptomatic intracerebral hemorrhage.[83]

Basic Research Progress

Imaging evaluation of cerebral microcirculation disorders after ischemic stroke

Advanced imaging techniques such as optical coherence tomography have been used to study cerebral microcirculation disorders after stroke. They can measure important parameters such as the diameter of branches of the middle cerebral artery, the count of perfused capillaries, capillary blood flow stasis, and flow velocity, providing a powerful tool for more accurate assessment of cerebral microcirculation disorders. Through these techniques, researchers can observe and quantify the changes in microcirculation after stroke in real time and further understand the occurrence mechanism and development process of microcirculation disorders.[89]

Relationship between cerebral microcirculation dysfunction and impaired neurovascular coupling after ischemic stroke

Studies have found that there is an association between impaired neurovascular coupling and microcirculation dysfunction in the area outside the ischemic core after ischemic stroke. After inducing cerebral ischemia by single-vessel photothrombosis in the branches of the middle cerebral artery in mice, the neurovascular coupling in the somatosensory cortex was studied by air-jet whisker stimulation. It was found that 3 h after stroke, the neurovascular coupling was already impaired in the area outside the ischemic core, and this impairment further deteriorated 24 h later. Although the resting blood flow and the dilation of the feeding artery were normal, there was still microcirculation dysfunction.[90]

Role of pericytes in cerebral microcirculation disorders after stroke

Studies have shown that pericytes play a key role in regulating cerebral capillary blood flow, and stroke can disrupt this regulatory role. After ischemic stroke, the diameter of capillaries covered by pericytes is smaller than that on the contralateral side, suggesting that pericytes may play a role in the reduction of capillary diameter and the impairment of neurovascular coupling caused by stroke. Meanwhile, it was also found that the capillaries accompanied by pericytes are not uniformly affected, and there are pericyte subpopulations with different sensitivities to ischemia and spreading depolarization injury.[90]

Interaction between inflammatory reaction and cerebral microcirculation disorders after stroke

Studies have found that the inflammatory reaction plays an important role in the occurrence and development of cerebral microcirculation disorders after stroke. After ischemic stroke, white blood cells will produce oxygen free radicals and inflammatory factors, such as interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor alpha, etc., which will damage endothelial cells, lead to endothelial dysfunction, and then trigger microcirculation disorders. Meanwhile, microcirculation disorders will further aggravate the inflammatory reaction, forming a vicious cycle.[91]

Relationship between blood–brain barrier disruption and cerebral microcirculation disorders after stroke

The disruption of the blood–brain barrier also plays an important role in cerebral microcirculation disorders after stroke. After ischemic stroke, the permeability of the blood–brain barrier increases, making the components in blood more likely to enter brain tissue, triggering brain edema and inflammatory reactions, and further aggravating microcirculation disorders. Meanwhile, microcirculation disorders will also affect the function and structural integrity of the blood–brain barrier. The two interact with each other and jointly lead to brain tissue damage.[92]

Research Prospects

After AIS recanalization, improving microcirculation is vital for patient prognosis. Clinical trials can focus on the following key research areas to explore adjuvant treatment efficacy:

Targeted drug therapy trials

Given the complex microcirculation disorder mechanisms post-recanalization, developing drugs targeting key pathological aspects is essential. For instance, drugs against platelet-neutrophil interactions can inhibit their binding, reducing microthrombus formation and improving microcirculatory flow. Design a multicenter, randomized, double-blind, placebo-controlled trial. Randomly assign patients to an experimental group (receiving the targeted drug) and a control group (receiving placebo). Assess patients’ functional recovery via the 90-day mRS score. Monitor microcirculatory blood flow parameters and platelet-neutrophil complex levels pre- and post-treatment to evaluate the drug’s impact on microcirculation and prognosis.

Real-time image-guided intervention trials

Real-time imaging technology enables dynamic microcirculation monitoring during treatment, facilitating treatment plan adjustments. For example, combining ultrasonic imaging with thrombectomy devices allows real-time observation of the thrombus and surrounding microcirculation during thrombectomy, enhancing thrombectomy accuracy and reducing microvascular damage. Conduct single- or two-arm clinical trials. In the experimental group, use real-time image-guided interventions; in the control group, apply traditional treatments. Evaluate the effectiveness of these interventions by comparing post-surgery infarct volume and microcirculation perfusion area between the two groups.

Biomarker-driven precision medicine

Identify biomarkers closely associated with post-recanalization microcirculation disorders in AIS. Develop personalized treatment plans based on patients’ biomarker levels. For example, detect endothelial injury-related biomarkers like soluble P-selectin and von Willebrand factor in patients’ blood. Offer targeted treatments (e.g., anti-endothelial injury drugs or cell therapy) to patients with elevated biomarker levels. Design a prospective cohort study. Stratify patients by biomarker levels and assign different treatment plans. Observe and compare clinical outcomes and microcirculation indicators among subgroups to explore biomarker-based precision treatment strategies.

Clinical trial design features

Adaptive platform design

As in the ESPRIT trial, set multiple dose groups simultaneously. Adjust dose selection and sample allocation in subsequent trials based on mid-term data analysis. This accelerates drug development, helps find the optimal treatment dose, improves R and D efficiency, and saves time and resources.

Multimodal imaging endpoints

Integrate imaging technologies such as CT perfusion imaging (CTP), MRI, and OPSI. CTP assesses cerebral blood perfusion, MRI shows brain tissue structure and infarct areas, and OPSI monitors microvessel morphology and blood flow in real time. Combining data from these technologies comprehensively and accurately quantifies microcirculation improvement, providing a solid basis for treatment evaluation.

Biomarker enrichment

Prior to the trial, measure patients’ baseline endothelial injury biomarkers. Select patients with high biomarker levels and a high risk of microcirculation disorders. This makes the trial population more homogeneous, enhances trial sensitivity and reliability, accurately evaluates treatment efficacy in high-risk patients, and supports clinical precision medicine.

Real-world data integration

Leverage registry studies (e.g., the ATTENTION IA study) to gather real-world patient treatment data, including basic information, treatment processes, and complications. Combine this data with RCT data. This overcomes RCT limitations in sample selection and trial environment, comprehensively evaluates treatment effectiveness and safety across different patient groups and clinical scenarios, and promotes research-to-practice translation.

Conclusion

The research prospects for cerebral microcirculation disorders after vascular recanalization focus on in-depth understanding of pathophysiological mechanisms, optimization of assessment methods, development of new drugs and treatment means, and translation and application of research results. These future studies will help improve the success rate of vascular recanalization treatment and the functional recovery of patients.

Author contributions

Zhifeng Li conducted the literature review and drafted the manuscript, Hongmei Niu to manuscript editing, Jiahao Chen contributed to conceptualization and supervision of the manuscript, Weili Li structured the manuscript, secured funding and performed critical revision. All authors read and approved the final version of the manuscript.

Ethical policy and institutional review board statement

Not applicable.

Data availability statement

Data sharing is not applicable to this article as no datasets were generated and/or analyzed during the current study.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

This study was sponsored by the National Natural Science Foundation of China (82360783), and the Natural Science Foundation of Shandong Province, China (ZR2024MH081).