Gamma aminobutyric acid (GABA) receptor agonists for acute stroke

Abstract

BackgroundGamma aminobutyric acid (GABA) receptor agonists have been shown to have a neuroprotectant e ect in reducing infarct size and improving functional outcome in animal models of cerebrovascular disease. However, the sedative e ects of GABA receptor agonists have limited their wider application in people with acute stroke, due to the potential risk of stupor. This is an update of a Cochrane Review first published in 2013, and previously updated in 2014 and 2016. ObjectivesTo determine the e icacy and safety of GABA receptor agonists in the treatment of acute stroke.

3′-Daidzein sulfonate sodium inhibits neuronal apoptosis induced by cerebral ischemia-reperfusion

“…Ischemia-reperfusion injury is a complex disorder caused by free radicals, NO, calcium overload, excitatory amino acids, inflammation and cell apoptosis. Many drugs have been used in the treatment of cerebral ischemia reperfusion injury, including calcium antagonists, free radical scavengers (24) and growth factors (25,26). Some traditional Chinese medicines have been shown to exert neuroprotective effects on cerebral ischemic injury (27)(28)(29).…”

The Roles of GABA in Ischemia-Reperfusion Injury in the Central Nervous System and Peripheral Organs

“…For a long time, barbiturates had clinically been used to control the intracranial hypertension in transient ischemia events in the operating room; some potential side effects (having a depressant effect on the cardiovascular and respiratory systems) might affect the applications (e.g., needing intensive care) [99]. Meanwhile, another system review [100] summarized that GABA receptor agonists (e.g., chlormethiazole) had better effects on patients with acute ischemic (within 12 hours) or hemorrhagic stroke. Some adverse events (e.g., somnolence and rhinitis) also occurred.…”

The neuroprotective effects of pregabalin after cerebral ischemia by occlusion of the middle cerebral artery in rats

“…It is also involved in secondary processes that lead to neuronal death after traumatic insult ( 7 , 8 ). Neuroprotective agents for treatment of acute stroke have received much attention and are expected to effectively protect vulnerable neurons and save ischemic penumbra ( 9 ). Several neuroprotective strategies target acute processes, including excitotoxicity, glutamate release, activation of NMDA receptors, calcium ion influx, and apoptosis leading to early cell death in the infarct core and periinfarct area ( 4 ).…”

“…Gamma aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system (CNS) that inhibits depolarization- and ischemia-induced glutamate release ( 9 ). GABA receptor agonists are conventional sedatives with neuroprotective effects in decreasing infarct size and improving functional outcomes in animal models of cerebraovascular disease.…”

“…GABA receptor agonists are conventional sedatives with neuroprotective effects in decreasing infarct size and improving functional outcomes in animal models of cerebraovascular disease. However, their sedative effects may be harmful, so their wider application in patients with acute stroke have been limited ( 9 ).…”