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| Drugs and dose | Treatments | Effects and mechanisms | References |
|
| GABA, γ-vinyl GABA (30-300 mol/L) in vitro | At 90 min after oxygen-glucose deprivation and reperfusion in rabbit brain slices | Reducing the release of glutamate and LDH and tissue water gain (GAT inhibitors) | [106] |
| Diazepam (10 mg/kg) | Injection (i.p.) at 30 and 90 min after transient gerbil brain ischemia | Reducing excitotoxic and oxidative stress by the peripheral benzodiazepine receptor in the outer mitochondrial membrane (GABAA receptor agonist) | [108] |
| Zolpidem (0.5, 1.0 mg/kg) | Injection (i.p.) following ischemic stroke in rats | Increasing numbers of cells containing BDNF (GABAA receptor agonist) | [113] |
| Propofol (20 mg/kg/h, 2 h) | Injection (i.p.) at the onset of reperfusion in the rat model of middle cerebral artery occlusion | Increasing the number of survival neurons and the expression of KCC2, extruding Cl- by upregulating the activity of the PKMζ/KCC2 pathway (GABAA receptor agonist) | [114, 115] |
| JM-1232 (500 μM) in vitro | During rat oxygen-glucose deprivation and reoxygenation | Reducing cell mortality in pyramidal neurons by GABAA receptor/decreased intracellular Ca2+ and other mechanisms | [116] |
| Tramadol (10, 20 mg/kg) | Injection (i.p.) before forebrain I/R in rats | Attenuating postischemic motor impairment by reducing the lipid peroxidation (GABAA receptor agonist) | [117] |
| Topiramate (80 mg/kg/day, twice daily) | Injection (i.p.) after occlusion of the bilateral carotid arteries in gerbils | Decreasing neurological deficit, attenuating neuronal loss by decreasing the expressions of procaspase-3, caspase-3, Bax/Bcl-2 ratio, GABAA receptor α1 and γ2 subunits, and KCC2 | [118] |
| Muscimol (1 mg/kg) and baclofen (20 mg/kg) alone | Injection (i.p.) at 6 hours and 1 day after rat I/R | Protecting neurons against death induced by I/R by enhancing NO synthase (GABAA,B receptor agonists) | [119] |
| Muscimol (1 mg/kg) and baclofen (20 mg/kg) together | Injection (i.p.) at 30 min before I/R in rats | Inhibiting NMDA receptor/Src-mediated signal amplification (GABAA,B receptor agonists) | [120] |
| Muscimol (1 mg/kg) and baclofen (15 mg/kg) together | Injection (i.p.) to rats at 30 min before ischemia | Neuroprotective effect by PI3K/Akt pathway (GABAA,B receptor agonists) | [121] |
| Muscimol (1 mg/kg) and baclofen (20 mg/kg) alone or together | Injection (i.p.) before I/R of rats | Attenuating the excitatory JNK3 apoptosis by increased assembly of the GluR6-PSD-95-MLK3 signaling (better combining effect of GABAA,B receptor agonists) | [122] |
| Baclofen (20 mg/kg) and muscimol (1 mg/kg) together | Injection (i.p.) at 30 min before rat ischemia | Increasing interaction of NO synthase with PSD95 and inhibiting protein phosphatase activity (combining effect of GABAA,B receptor agonists) | [119] |
| R-Phenibut (10, 50 mg/kg) | Injection (i.p.) at 2 h and 7 days following reperfusion in transient middle cerebral artery occlusion in rats | Improved histological outcome and reduced brain volume; increase of BDNF and VEGF gene expressions (by activating GABAB receptor and α2-δ subunit of the voltage-dependent Ca2+ channel) | [123] |
| Baclofen (50 mg/kg) | Injection following (i.p.) ischemic insult in the ischemic gerbils | Preventing the loss of hippocampal CA1 pyramidal cells and calmodulin-dependent protein kinase II but not memory deficits (GABAB receptor agonist) | [124] |
| Baclofen (1.25, 2.5 mg/mL) | Two weeks after chronic cerebral hypoperfusion rats (i.p.) | Increasing Bcl-2/Bax ratio and activating Akt, GSK-3β, and ERK which suppressed autophagy (GABAB receptor agonist) | [125] |
| Baclofen (25 mg/kg) | Injection (i.p.) at 17 d after permanent occlusion of the bilateral common carotid arteries in rats | Improving GABAB2 receptor expressions in neural surface, restoring the levels of BDNF, TrkB, and NCAM, and reversing the increased surface expressions of Kir3 (GABAB receptor agonist) | [126] |
| Baclofen (0.5, 2, and 5 μmol/L) in vitro | At 1 hour from the beginning of I/R in rat hippocampal slice cultures | Neuroprotection (GABAB receptor agonist) | [127] |
| Baclofen (500 mg/L) | Pretreatments (i.p.) before rat I/R | Stimulating neutrophil-directed migration by PI3K (GABAB receptor agonist) | [128] |
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