Glutamate Is a Marker for Cerebral Ischemia in Cortical but Not Deep Infarcts

Abstract

We analyzed glutamate levels in cerebrospinal fluid (CSF) with respect to cerebral infarct topography in 67 patients with cortical infarcts and 78 with deep infarcts of less than 24 h duration. Infarct volume and topography were determined on repeated cerebral CT performed between 4 and 7 days after admission. Stroke severity was evaluated by the Canadian Stroke Scale (CSS) at 48 h after inclusion. Glutamate concentration in CSF was 8.4 ± 4.9 µmol/l in patients with cortical infarcts and 6.5 ± 5.2 µmol/l in patients with deep infarcts (p = 0.028). In cortical infarcts, glutamate levels correlated with the CSS score (Spearman coefficient –0.601, p < 0.001) and with the infarct volume (Spearman coefficient 0.671, p < 0.001). In the logistic regression analysis, glutamate was an independent predictor for stroke severity (high: CSS score < 5; low: CSS score ≧ 5) after controlling for age, inclusion delay, body temperature, glucose levels and fibrinogen (odds ratio = 1.3; 95% confidence interval= 1.07–1.67). Glutamate was not related significantly with the severity and size of deep cerebral infarcts. Early neurological deterioration was more frequent in cortical infarcts than in deep infarcts (43 vs. 19%, p < 0.001), and was independently related to glutamate levels in CSF. These results suggest that drugs that inhibit or antagonize glutamate may be useful particularly in cortical infarcts.

Nitric Oxide–Related Brain Damage in Acute Ischemic Stroke

“…This argues against a glutamate-calcium-dependent generation of NO, because glutamate release is significantly higher in cortical than in subcortical infarcts, probably owing to a higher number of glutamatergic neurons in the gray matter. 40 The involvement of NO in the progression of cerebral infarction is an appealing hypothesis. The present study shows that NO plays a part in early neurological deterioration, a fact that has been attributed to the expansion of the ischemic area.…”

Levels of Anti-Inflammatory Cytokines and Neurological Worsening in Acute Ischemic Stroke

“…Methods to calculate infarct volume and infarct topography definitions were previously reported. 6,19 For cytokine determination, blood samples of patients were collected on admission in tubes with potassium edetate, centrifuged at 3000g for 5 minutes, and immediately frozen and stored until analysis (5 to 7 years at Ϫ80°). Mean admission delay from stroke onset was 8.2Ϯ5.7 hours (rangeϭ1.5 to 23 hours).…”

Deterioration in Acute Ischemic Stroke as the Target for Neuroprotection

“…Plasma glutamate levels in CSF remained abnormally high for at least 24 h in those patients who suffered END whereas they returned to normal levels in <6 h in patents who did not suffer from progressing stroke [39]. Recently, in a study focused on patients with hemispheric stroke of <12 h evolution, we again found higher concentrations of glutamate in patients with END and that glutamate levels mediate DWI lesion growth in these patients [45]. Beyond the penumbral area, tissue is still at risk and there is a high correlation between baseline and 24 h glutamate levels and the volume of the peripenumbral area which subsequently becomes infracted [46].…”

“…In 1996, we found high concentrations of glutamate in the CSF and plasma of stroke patients with <24 h of onset [44, 45]. Plasma glutamate concentrations of >200 µmol/l within the first 24 h of stroke onset were found to have a 97% positive predictive value for the subsequent progression of cortical, subcortical and lacunar ischemic strokes independently of the infarct volume and stroke severity at admission [22].…”