Serum Amino Acid Levels after Permanent Middle Cerebral Artery Occlusion in the Rat

Abstract

Background and Purpose: High levels of glutamate in plasma and cerebrospinal fluid (CSF) have been demonstrated in patients with acute ischemic stroke. Whereas this glutamate increase in CSF is only evidenced during the first 6 h in stable ischemic stroke, it is sustained for 24 h in progressing stroke. The aim of this investigation was to study the evolution of serum glutamate levels after stroke in a rat model of permanent cerebral artery occlusion. Methods: Glutamate, glycine, aspartate, taurine and tryptophan were measured by high-performance liquid chromatography from serum samples taken before and at different times after permanent middle cerebral artery occlusion (MCAO) and from sham-operated rats. Results: After MCAO, a 3-fold increase in glutamate and a 2-fold increase in glycine and aspartate were observed in rat serum. The onset of this amino acid increase began 4–6 h after ischemic induction, reached peak values at 8–24 h and returned to preischemic values by 48–72 h. Serum concentrations of taurine and tryptophan were not modified after MCAO. Sham-operated rats did not exhibit changes of basal amino acid concentrations in serum. Conclusions: The serum excitatory amino acid profile in this experimental model confirms that the early detection of increased concentrations of glutamate and glycine at systemic circulation observed in patients with acute stroke is a consequence of the cerebral ischemic process.

The characteristics of therapeutic effect of pinocembrin in transient global brain ischemia/reperfusion rats

“…Increased Glu levels may lead to the opening of the BBB in cerebral ischemia (András et al 2007), subsequently causing the excessive efflux of excitatory amino acids from the brain to peripheral circulation during reperfusion termed "washed-out" (Erecińska et al 1984). This is indicated by the findings that the onset of excitatory amino acids elevation in serum began 4-6 h after ischemic induction (Puig et al 2000). Thus, in this experiment it was normal to record a decline in the amino acids levels 4 h after blood reflow in the 4-VO rat brain.…”

Neurological Deterioration in Acute Lacunar Infarctions

“…26 This hypothesis is supported by the finding of a very high correlation between CSF and plasma concentrations of glutamate in human stroke 11 and the sharp increase in plasma glutamate found 4 hours after permanent middle cerebral artery (MCA) occlusion in a rat stroke model, which is not observed for other amino acids unrelated to the excitotoxic theory of stroke damage. 27 The role of glutamate in lacunar stroke is unknown because few patients were included in previous investigations. It has been proposed that glutamate does not exert a neurotoxic action in white matter ischemia because of a lack of synaptic glutamate receptors.…”

“…The lack of coincidence in the results for lacunar and territorial infarctions cannot be attributed to a different interval from stroke onset to sampling because this interval was 10 hours in the present series and 11 hours in our previous study. 11 Increased levels of glycine in plasma were obtained 4 hours after permanent MCA occlusion in a rat stroke model, 27 so glycine levels in the brain are likely to be detected in peripheral blood in large infarctions. These data suggest that the discrepancy might be explained by a smaller release of glycine in small infarctions.…”

Progesterone Treatment in Two Rat Models of Ocular Ischemia

“…8 In the MCAO model, the cause of retinal injury is partially local, due to the filament reducing blood flow to the eye, and partially systemic, due to effects of the infarct in the brain. The systemic effects include a 3-fold increase in glutamate levels, 71 which may explain the increase in GS in contralateral as well as MCAO retinas. In the MCAO model, ERG deficits and increased GS are observed at 2 days post MCAO, suggesting extracellular glutamate as a mechanism.…”