As ischemic stroke is associated with an excessive release of glutamate into the neuronal extracellular space, a decrease in blood glutamate levels could provide a mechanism to remove it from the brain tissue, by increasing the brain-blood gradient. In this regard, the ability of glutamate oxaloacetate transaminase (GOT) to metabolize glutamate in blood could represent a potential neuroprotective tool for ischemic stroke. This study aimed to determine the neuroprotective effects of GOT in an animal model of cerebral ischemia by means of a middle cerebral arterial occlusion (MCAO) following the Stroke Therapy Academic Industry Roundtable (STAIR) group guidelines. In this animal model, oxaloacetate-mediated GOT activation inhibited the increase of blood and cerebral glutamate after MCAO. This effect is reflected in a reduction of infarct size, smaller edema volume, and lower sensorimotor deficits with respect to controls. Magnetic resonance spectroscopy confirmed that the increase of glutamate levels in the brain parenchyma after MCAO is inhibited after oxaloacetate-mediated GOT activation. These findings show the capacity of the GOT to remove glutamate from the brain by means of blood glutamate degradation, and suggest the applicability of this enzyme as an efficient and novel neuroprotective tool against ischemic stroke.

Background and Purpose-Iron plays a detrimental role after experimental intracerebral hemorrhage (ICH). This study investigates whether high-serum ferritin levels are associated with poor outcome in patients with ICH. Methods-We studied 92 consecutive patients with primary hemispheric ICH within the first 12 hours from onset of symptoms (median, 3.3 hours). National Institute of Health Stroke Scale score, ICH, and peripheral edema volumes were measured at admission, 72 hours, and 7 days. Serum levels of ferritin and biomarkers of the inflammatory response were determined. The adjusted effect of ferritin on the full range of Rankin scale was analyzed by a general linear model. Results-Fifty-one patients (55.4%) had poor outcome (Rankin score Ͼ2). Older age, higher stroke severity, larger hematoma volume, intraventricular extension, mass effect, and higher IL-6 and ferritin levels at baseline (270. ron has been involved in cerebral injury after intracerebral hemorrhage (ICH) in experimental studies. Free iron released after erythrocyte lyses and from ferritin stores may have a role in oxidative stress, glutamate release, and inflammatory response after a hemorrhagic brain injury. 1-3 Iron chelators like deferoxamine can reduce brain edema and improve neurological function in experimental models of ICH. 4 Few data exist about clinical evidence of iron toxicity in ICH patients. 5 We collected our data with the objective to test if serum ferritin levels are associated with poor outcome in patients with ICH. Subjects and MethodsWe prospectively evaluated 100 consecutive patients with a primary supratentorial ICH admitted within the first 12 hours from onset of symptoms in 3 hospitals during 1 year. Exclusion criteria were previous disability, severe alcohol consumption, inflammatory or infectious liver, renal, hematologic diseases or cancer, secondary intracerebral hemorrhage, and coma. We further excluded 3 patients lost to follow-up and 5 patients in whom admission cranial CT was not available for volume calculations. The study was approved by the ethics committees of the participating centers and informed consent was signed by patients or their relatives. All patients were admitted at an acute stroke unit and treated according to the guidelines of the European Stroke Initiative. 6 Stroke severity was quantified using the National Institute of Health Stroke Scale score. Functional outcome was evaluated at 3 months using the modified Rankin scale, and poor outcome was defined as modified Rankin scale score Ͼ2.Cranial CT was performed at admission, 72 hours, and 7 days. ICH and peripheral hypodensity volume were measured using the formula of the ellipsoid, and edema volume was calculated by subtracting the volume of the ICH from that of the total lesion. Mass effect was considered when ventricular asymmetry or shifting of the midline structures was observed. All CT scans were centrally evaluated by an investigator who was masked to clinical data. ICH and edema growth ratios were calculated as: final volumeϪinitial vo...