The role of gama aminobutyric acid (GABA) in acute ischemic stroke
Background: GABA neurotransmission causes membrane hyperpolarization which may counterbalance the toxic effects of glutamate during cerebral ischemia. Although the neuroprotective action of a GABA agonist (Clomethiazole) on acute ischemic stroke is currently being investigated, the importance of GABA in human stroke is unknown. Objective: to analyze whether the concentrations of GABA were related to early stroke outcome in 258 patients with an acute hemispheric cerebral infarction. Methods: GABA was measured using HPLC in blood and CSF samples obtained within 24h from stroke onset, and in blood 48h after admission. Stroke was classified according to Bamford’s scheme. Deterioration was diagnosed if Canadian stroke scale dropped 1 or more points during the first 48h after inclusion. The relative importance of GABA for neurologic worsening was evaluated by logistic regression analysis. Results: GABA concentrations (nmol/L) in plasma and CSF were significantly lower in TACS (108±86 and 44±20) than in PACS (240±164 and 87±60), LACS (377±136 and 134±43), and POCS (374±137 and 134±35) (all p<0.0001). There was a significant linear correlation between plasma and CSF values of GABA (r=0.70, p<0.001). Neurologic deterioration occurred in 87 patients (33.7%). In TACS and PACS, mean plasma and CSF levels of GABA at admission were three fold lower in patients with progressing stroke than in those without worsening (all p<0.0001); in LACS and POCS they were 40% lower in patients with progression (p<0.01). GABA concentrations of less than 190 nmol/L in plasma (OR,13.0; 95%CI, 3.8 to 44.8), and of less than 82 nmol/L in CSF (OR,20.3; 95%CI, 5.6 to 71.8) were significantly associated with neurologic worsening after adjusting for age, inclusion delay, serum glucose, body temperature, and stroke severity on admission, and ultimate infarct volume. Mean plasma GABA levels did not change at 48h in patients with deterioration, but increased a 17% in those who improved or remained stable (Wilcoxon, p<0.001). Conclusions: Early neurologic deterioration in acute ischemic stroke is related to low GABA concentrations in blood and CSF, particularly in patients with total or partial anterior circulation syndromes.