Table 1.
Rodent models of adult stroke
| Etiology | Model | Advantages | Disadvantages |
|---|---|---|---|
| Induced stroke models | |||
| Global ischemia - acute | Four-vessel occlusion (13–15) | Reversible forebrain ischemia may be induced in awake animals. | Two-stage operative procedure. Occurrence of seizures. Variable outcomes in different rat strains. |
| Two-vessel occlusion (16,17) | One-stage operative procedure. Reversible ischemic forebrain injury. | Necessity of systemic hypotension (exsanguination). | |
| Asphyxial cardiac arrest (18,19) | Whole brain ischemia followed by related systemic changes such as hypoxemia, acidosis, systemic inflammation, hypercortisolemia, hyperglycemia. | Intensive postsurgery care (assisted ventilation, supplemental fluids). Body temperature during first days of recovery strongly influences outcome. | |
| Global ischemia - chronic | Bilateral common carotid artery ligation (20) | Produces white matter changes similar to leukoa raiosis seen on CT and MR brain scans in humans. | Approximately 20% case fatality within one-week of procedure. Damage to visual pathway may compromise neurobehavioral assessment. |
| Bilateral common carotid artery stenosis (21) | Produces milder reduction in cerebral blood flow than ligation model earlier, with white matter lesions but sparing of visual pathways and gray matter | Lesions take two-weeks to develop | |
| Focal ischemia | Endovascular MCAO (22–24) | Most frequently used method in rodents. Easy to perform permanent or transient ischemia. | Risk of vessel rupture (SAH). Postsurgical hyperthermia. |
| Surgical MCAO (25–27) | Better control of occlusion site and therefore less variability. | Necessity of craniotomy. | |
| Thromboembolic MCAO (28) | Mimics most common cause of ischemic stroke in humans. Suitable to investigate thrombolytic therapies. | Higher variability in lesion size, location, and occur rence of spontaneous reperfusion. | |
| Photothrombosis (29–31) | Ability to induce infarct in variable cortical location. Less invasive procedure. | Less relevance to human condition. Occurrence of spontaneous reperfusion. | |
| Intracarotid injection of SDS detergent (32) | Selective perforating artery occlusion caused by in situ small vessel injury including endothelial damage and fibrin thrombus. | Unpredictable distribution of infarcts. | |
| Cortical pial artery occlusion (12) | Arterial occlusion with forceps or photochemical irradiation produces small cortical infarcts. | ||
| Subcortical injection of endothelin-1 (12) | Production of subcortical ischemic lesions in dose-dependent manner. | Several microvessels affected simultaneously - cannot accurately target single perforating vessel. | |
| Selective intraluminal thread occlusion of anterior choroidal/hypothalamic artery (12) | Production of precise area of subcortical infarction in defined arterial territory | Difficult to place thread accurately - MCAO occurs inadvertently in significant proportion of animals. | |
| SAH | Endovascular perforation (33,34) | Rupture of intracranial vessels reflects the clinical condition of aneurysmal SAH in humans. | Mortality reaches 37–5-50% within 24 h after SAH induction. Variable severities. |
| Intracisternal blood injection (35,36) | SAH severity may be regulated by blood quantity and number of injections. | Nonphysiological blood distribution. | |
| ICH | Intracerebral injection of bacterial collagenase (37) | Rupture of intracerebral vessels mimics ICH in humans. Allows investigations of delayed hematoma expansion and hemostasis. | Bacterial collagenase may induce inflammatory responses. Variability in hematoma size. |
| Intracerebral blood injection (38,39) | Injection of variable blood compositions. No confounding inflammation. | Matched to hematoma size, neurofunctional deficits resolve more rapidly compared with the collagenase injection model. | |
| Spontaneous stroke models | |||
| Focal ischemia | SHRSP (40) | Similar vascular and parenchymal pathological processes to human small vessel disease and lacunar stroke. | Spontaneous strokes do not occur until 20 weeks although can be hastened by high salt diet. |
| IHR (41) | Animals given saline rapidly develop scattered microscopic areas of cortical infarction. | Vascular pathology not extensively studied. | |
| ICH | R+/A+ mice (42) | Animals given high-salt diet and L-NAME develop spontaneous intracerebral hemorrhage | Strokes take several weeks to develop. Vascular pathology not much studied. |
CT, computed topography; ICH, intracerebral hemorrhage; IHR, inducible hypertensive rat; MCAO, middle cerebral artery occlusion; R+/A+ mice, transgenic mice expressing human rennin and human angiotensinogen; SAH, sub-arachnoid hemorrhage; SHRSP, spontaneously hypertensive stroke prone rat; L-NAME, N(omega)-nitro-L-arginine methyl ester.