Blood levels of glutamate oxaloacetate transaminase are more strongly associated with good outcome in acute ischaemic stroke than glutamate pyruvate transaminase levels

Abstract

Ischaemic stroke is associated with an excessive release of glutamate in brain. GOT (glutamate-oxaloacetate transaminase) and GPT (glutamate-pyruvate transaminase) are two enzymes that are able to metabolize blood glutamate facilitating the lowering of extracellular levels of brain glutamate. Our aim was to study the association between blood levels of both enzymes and stroke outcome in patients with acute ischaemic stroke. We prospectively studied 365 patients with first ischaemic stroke<12 h. Glutamate, GOT and GPT levels were determined in blood samples obtained at admission. We considered functional outcome at 3 months [good outcome: mRS (modified Rankin Scale)≤2; poor outcome mRS >2], END (early neurological deterioration) in the first 72 h [increment ≥4 points in NIHSS (National Institutes of Health Stroke Scale)] and infarct volume [CT (computed tomography) at 36-72 h] as end points. We have found an inverse correlation between GOT and GPT levels and blood glutamate levels. Patients with poor outcome showed lower levels of GOT (11.9±8.2 compared with 22.7±10.2 m-units/ml, P<0.0001) and GPT (19.5±14.3 compared with 24.7±20.3 m-units/ml; P=0.004). A negative correlation has been found between GOT (Pearson coefficient=-0.477, P<0.0001) and GPT (Pearson coefficient=-0.116; P=0.027) levels and infarct volume. Patients with END showed higher levels of blood glutamate (381.7±97.9 compared with 237.6±114.0 μmol/l, P<0.0001) and lower levels of GOT (10.8±6.7 compared with 18.1±10.8 m-units/ml; P<0.0001). This clinical study shows an association between high blood GOT and GPT levels and good outcome in ischaemic stroke patients, this association being stronger for GOT than GPT levels.

The Effect of Blood Glutamate Scavengers Oxaloacetate and Pyruvate on Neurological Outcome in a Rat Model of Subarachnoid Hemorrhage

“…Campos et al further showed that lower blood glutamate levels and higher levels of GOT were associated with better neurological outcome in patients after ischemic stroke [41][42][43]. Considering the close relationship between low blood and CSF glutamate levels, the results of the current study suggest that oxaloacetate and pyruvate provide their neuroprotective properties via a glutamate-scavenging mechanism.…”

“…The efflux of glutamate into the blood resulted in increased concentrations of radiolabeled glutamate in the blood and its disappearance from the CSF [34]. Magnetic resonance spectroscopy confirmed that blood glutamate scavengers oxaloacetate and GOT are capable of decreasing ECF glutamate concentrations via blood glutamate elimination in a rat model of experimental focal ischemia [41][42][43].…”

“…This in turn facilitates the brain-to-blood glutamate efflux, thereby limiting the neurotoxic effects of glutamate. Treatments with blood glutamate scavengers oxaloacetate, pyruvate, GOT, and glutamatepyruvate transaminase have been shown to effectively improve neurological recovery after traumatic brain injury (TBI) [35][36][37][38] and stroke [39][40][41][42][43], with a concomitant decrease in blood glutamate levels [30,34].…”

A novel mechanism of neuroprotection: Blood glutamate grabber

“…57,58 Similar to previous studies with GOT, GPT levels were associated with lower levels of blood glutamate, better functional outcome, reduced infarct volume, and lower percentages of early neurological deterioration, although this association was stronger for GOT than GPT levels. 50 Similarly, in experimental studies, OxAc presented stronger protective effects than pyruvate. 57,58 Hemodialysis and peritoneal dialysis Another interesting and potentially useful method for reducing blood glutamate concentrations is the use of dialysis to filter the blood and remove excess glutamate.…”

“…To test this hypothesis, two independent clinical and observational studies were performed, in which the primary end point was functional outcome at three months. 50,51 In these studies, patients with good outcomes showed lower glutamate levels and higher GOT levels in blood samples collected at admission. A significant inverse correlation was observed between GOT and glutamate levels.…”