Analysis of the NMDA in Focal Cerebral Ischemia in Rats

Abstract

SUMMARY: NMDAR (N-methyl-D-aspartate receptor) is one subtype of ionotrophic glutamate receptor which is extensively distributed in the central nervous system (CNS). In the mammalian CNS, NMDAR serves prominent roles in the pathophysiologic process of cerebral ischemia. This study aimed to investigate the pattern of expression of protein and gene of the excitatory neurotransmitter NMDAR in experimental focal cerebral ischemia and the hole of neuroprotection with hypothermia and ketoprofen. 120 rats were randomly divided into 6 groups (20 animals each): control -no surgery; sham -simulation of surgery; ischemic -focal ischemia for 1 hour, without reperfusion; ischemic + intraischemic hypothermia; ischemic + previous intravenous ketoprofen, and ischemic + hypothermia and ketoprofen. Ten animals from each experimental group were used to establish the volume of infarct. Transient focal cerebral ischemia was obtained in rats by occlusion of the middle cerebral artery with an intraluminal suture. The infarct volume was measured using morphometric analysis of infarct areas defined by triphenyl tetrazolium chloride and the patterns of expression of the protein and gene NMDA were evaluated by immunohistochemistry and quantitative real-time PCR, respectively. Increases in the protein and gene NMDA receptor in the ischemics areas were observed and these increases were reduced by hypothermia and ketoprofen. The increase in the NMDA receptor protein and gene expression observed in the ischemic animals was reduced by neuroprotection (hypothermia and ketoprofen). The NMDA receptor increases in the ischemic area suggests that the NMDA mediated neuroexcitotoxicity plays an important role in cell death and that the neuroprotective effect of both, hypothermia and ketoprofen is directly involved with the NMDA. 980 (Dietrich et al.), has proved to be effective in providing protection after cerebral ischemia. Anti-inflammatory agents are used to attenuate the inflammatory response triggered by the ischemic phenomenon (Dietrich et al.), with emphasis on ketoprofen (Asanuma et al.; Dias et al.), a non steroid agent with a very potent analgesic and anti-inflammatory action, acting as a possible antagonist of the of the NMDA receptors (McCormack et al., 1994).One of the more intriguing reactions of cells to a severe metabolic insult is a change in their gene expression, which has become an important focus of interest in cerebral ischemia since several regulatory genes play an important role in the various aspects of infarct pathophysiology (Schneider et al., 2004). This study aimed to investigate the pattern of expression of the protein and gene NMDAR, in an experimental model of transient focal cerebral ischemia without reperfusion and the hole of neuroprotection with hypothermia and ketoprofen. MATERIAL AND METHODOne hundred and twenty adult male rats (Rattus norvegicus) weighing 280-310 g were used and the animals were randomly divided into 3 experimental groups: control (C), 20 animals sacrificed without being submitted to the surgic...

Effects of transcranial direct current stimulation on the glutamatergic pathway in the male rat hippocampus after experimental focal cerebral ischemia

“…The previous study has demonstrated that the NMDAR1 receptor protein and gene expression in the brain tissue of rats enhanced significantly after focal cerebral ischemia (Tirapelli et al, 2012). Zaric et al (2018) showed that there was a significant increase in the protein levels of VGLUT1, NMDAR1, and NMDAR2B at the 48th h of reperfusion in the hippocampus tissues of rats in which 15 min transient global cerebral ischemia had occurred, but the protein levels of NMDAR2A did not change.…”