Molecular Mechanism	Drug/Technology	Cerebral hypoxia disease	Model	In vivo/In vitro	Regulatory Factors	References
MAPK	IHT	AD	8-Month-old APP/PS1 mice + PAM model	In vivo + In vitro	The activation of TFEB induced by IHT is associated with the inhibition of the AKT-MAPK-mTOR pathway	Wang et al. (2023a, b, c, d)
	HP-BMSCs	Cardiac arrest can result in cerebral ischemia–reperfusion injury and poor neurological outcomes	a cardiac arrest rat model	In vivo	HP-BMSCs attenuate brain injury by reducing the expression of HMGB1, TLR4, NF-κB p65, p38 MAPK, and JNK in the cerebral cortex	Tang et al. (2023a, b)
	Intermittent fasting along with hydroalcoholic extract of Centella-asiatica	ischemic stroke	sub-acute hypoxia-induced ischemic stroke in adult zebrafish	In vivo	Subacute hypoxia can promote behavioral changes, free radical production, and alterations in brain tissue oxidative stress status (SOD, GSH-Px, and LPO) in zebrafish, accompanied by mitochondrial dysfunction (complexes I, II, and IV), neuroinflammation (IL-10, IL-1β, and TNF-α), and alterations in signaling molecules (AMPK, MAPK, GSK-3β, Nrf2)	Bindal et al. (2024)
	Sanpian decoction	cerebral ischemia–reperfusion injury	the rat model of MCAO/R	In vivo	Sanpian decoction upregulates SIRT1 expression, downregulates p-ERK/ERK and HIF-1α levels, increases cerebral blood flow, improves neurological function, and reduces neuronal apoptosis	Yang et al. (2024a, b, c)
	rhEPO	TBI and delayed hypoxemia	murine model of TBI and delayed hypoxemia	In vivo	rhEPO enhances neural regeneration and repair after cerebral ischemia by activating the MAPK/CREB signaling pathway, aiming to affect neurogenesis, neuroprotection, and synaptic density following cerebral ischemia	Celorrio and Friess (2023), Celorrio et al. (2022)
	Naoluoxintong formula and its split prescriptions	cerebral ischemia–reperfusion	MCAO/R rats with QDBS	In vivo	Naoluoxintong formula and its split prescriptions effectively promote cerebrovascular regeneration in a rat model of cerebral ischemia reperfusion by significantly inhibiting the activity of p38 MAPK and effectively activating a series of factors closely related to angiogenesis, including VEGFA, VEGFR2, CD31, Ang1, Ang2, and Tie2	Xiao et al. (2023)
	Hydrogen Gas	Neonatal HIE	a rat model of neonatal HIBI + OGD/R nerve growth factor-differentiated PC12 cells	In vivo  + In vitro	Hydrogen attenuates hypoxic-ischemic brain injury in neonatal rats by regulating the MAPK/HO-1/PGC-1α pathway. Hydrogen activates MAPKs, leading to the induction of HO-1 expression. Subsequently, HO-1 upregulates the expression of PGC-1α and SIRT1, thereby enhancing cellular antioxidant defense capabilities and mitigating brain injury	Wang et al. (2020a, b)
AMPA receptors	Ampakines	repeated hypoxic episodes	adult male Sprague–Dawley rats	In vivo	Ampakine regulates AMPA receptors through allosteric modulation, affecting the efficiency and intensity of synaptic transmission, thereby enhancing the promoting effect of hypoxia on diaphragmatic movement	Thakre and Fuller (2024)
	two PHDIs, JNJ-4204193 and roxadustat	acute ischemic stroke	isolated rat hippocampal slices	In vitro	APHDIs regulate synaptic transmission and plasticity by influencing the quantity, trafficking, and expression of the GluA2 subunit of AMPA receptors, thereby exerting neuroprotective effects during ischemic stress	Moreton et al. (2023)
	Taxifolin	ischemic stroke	hippocampal cell cultures after 40 min of OGD/R	In vitro	Taxifolin potentially enhances the function of AMPA receptors by increasing the expression of genes encoding AMPA receptor subunits, thereby affecting neuronal signal transmission and excitability, while also reducing the expression of pro-oxidant enzyme NOS and pro-inflammatory cytokine IL-1β	Turovskaya et al. (2019)
	Icariin	neonatal epilepsy	hypoxia-induced neonatal epilepsy rats	In vivo	Icariin protects against neuronal damage and improves cognitive function in neonatal epileptic rats induced by hypoxia through modulation of the AMPA receptor GluR2/ERK I/II pathway	Guo et al. (2020)
	Fingolimod	neonatal epilepsy	hypoxia-induced neonatal seizure pups	In vivo	Fingolimod may affect memory function and synaptic transmission by regulating the expression or function of AMPA receptors, particularly their GluR2 subunit	Hajipour et al. (2023)
NMDA receptors	Telaprevir	Ischemic Stroke	ischemic stroke mice	In vivo	Terawer alleviates cerebral ischemic injury by affecting NMDA receptors (particularly the GluN2B subunit) and inhibiting MALT1, thereby improving neural function in mice	Zhang et al. (2023a, b, c)
	Carbamathione	stroke	PC-12 cell cultures as a cell-based model and BCAO for stroke	In vivo + In vitro	Carbamathione attenuated NMDA-mediated glutamate currents, resulting in the activation of the AKT signaling pathway. This led to an increase in the expression of cell survival biomarkers such as Hsp 27, P-AKT, and Bcl-2, as well as a decrease in the expression of cell death markers like Beclin 1, Bax, and cleaved caspase-3	Modi et al. (2023)
	brain machine interface techniques	neurocognitive disorders	mice	In vivo	Training mice through brain machine interface techniques to enhance their low gamma power in local field potentials led to an increase in the transcriptional level of NMDA receptors	Shi et al. (2024)
	Amantadine	brain injury	SH-SY5Y and HEK293 cells	In vitro	Amantadine alleviates hypoxia-induced mitochondrial oxidative neurotoxicity, apoptosis, and inflammation by regulating NMDA receptors to reduce Ca2 + influx, and inhibiting TRPM2 and TRPV4 channels	Öcal et al. (2022)
	esketamine and buprenorphine	panic disorder	male Wistar rats exposed to acute hypoxia	In vivo	Esketamine and buprenorphine exhibited similar anti-panic effects in acute hypoxic rats, with esketamine potentially acting through antagonism of NMDA receptors, while the effects of buprenorphine were primarily related to its interaction with opioid receptors	Maraschin et al. (2022)
	Fingolimod	neonatal epilepsy	hypoxia-induced neonatal seizure pups	In vivo	Fingolimod may exert neuroprotective effects by regulating the expression or function of NMDA receptors, particularly the NR2A subunit, through mechanisms such as modulating calcium influx and altering receptor phosphorylation states	Hajipour et al. (2023)
BDNF	Asiatic acid	Prenatal hypoxia	intrauterine hypoxia-exposed zebrafish	In vivo	Asiatic acid may exert neuroprotective effects by increasing the expression of BDNF, which plays a crucial role in the growth, differentiation, and survival of neurons	Ariani et al. (2023)
	Sub-dose anesthetics combined with chloride	Cerebral ischemia-hypoxia	CCH model	In vivo	Sub-dose anesthetics combined with chloride regulators can significantly reduce hypoxic injury, improve cognitive function, decrease intracellular chloride accumulation, reduce cell death, restore the compensatory effect of GABA, and increase the expression of BDNF	Yang et al. (2024a, b, c)
	Pterostilbene	chronic intermittent hypoxia	CIH mouse model	In vivo	Pterostilbene alleviates chronic intermittent hypoxia-induced oxidative stress injury in neural cells by upregulating BDNF expression, modulating immune responses (increasing the levels of anti-inflammatory Th2 cells and Treg cells while decreasing the levels of proinflammatory Th1 cells and Th17 cells), and inhibiting glial cell activation through the p-ERK signaling pathway	Liu et al. (2023)
	Hypoxic Preconditioning	hypoxia/ischemia injury	ICR mice	In vivo	Hypoxic Preconditioning downregulates the expression of DNMT3A and DNMT3B, resulting in decreased DNA methylation levels in the BDNF gene promoter region. This reduction in methylation levels leads to upregulation of BDNF expression. The upregulated BDNF further activates the BDNF/TrkB signaling pathway, exerting positive effects on neuronal growth, differentiation, and function, ultimately promoting learning and memory capabilities in mice	Zhang et al. (2023a, b, c)
	A new peptide, VD11	spinal cord injury	PC12 cells subjected to hypoxia  + rats with spinal cord injury	In vitro + In vivo	VD11 promotes the secretion and expression of BDNF, upregulating its levels in injured spinal cords. BDNF subsequently binds to its receptors, activating downstream signaling pathways (such as AMPK and AKT signaling pathways), thereby promoting neuronal growth, differentiation, and survival. Ultimately, this leads to improved structural and functional recovery following spinal cord injury	Li et al. (2023a, b)
	Dexmedetomidine	HIBD in neonates	HIBD was induced in postnatal day 7 rats	In vivo	Dexmedetomidine upregulates the expression of BDNF, subsequently activating its receptor TrkB and downstream CREB signaling pathway. This series of signal transduction processes promotes hippocampal neurogenesis and affects the polarization of astrocytes, thereby alleviating neuronal damage and cognitive dysfunction caused by HIBD	Chen et al. (2024)