scholarly journals Short Therapeutic Window for MK-801 in Transient Focal Cerebral Ischemia in Normotensive Rats

1996 ◽  
Vol 16 (1) ◽  
pp. 107-113 ◽  
Author(s):  
I. Margaill ◽  
S. Parmentier ◽  
J. Callebert ◽  
M. Allix ◽  
R. G. Boulu ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Nmda Receptors ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuroprotective Activity ◽  
Therapeutic Window ◽  
Left Middle Cerebral Artery ◽  
Mk 801 ◽  
Transient Focal Cerebral Ischemia

The present study investigates the role of N-methyl-D-aspartate (NMDA) receptors in a model of transient focal cerebral ischemia in normotensive rats. The left middle cerebral artery and both common carotid arteries were occluded for 60 min. Preliminary studies indicated that this gave reproducible infarctions of the cortex and striatum. These infarctions were the result of severe ischemia followed by complete reperfusion after clamp removal, as showed by striatal tissue Po2 monitoring. Microdialysis indicated that glutamate concentration increased immediately after occlusion and returned to the baseline value 40 min after clamp removal. MK-801 (1 mg kg−1 i.v.), an antagonist of the NMDA glutamatergic receptor, reduced the cortical infarct volume by 29% (p < 0.001) and the striatal infarct volume by 14% (p < 0.05) when given just prior to ischemia, but had no neuroprotective activity when given 30 min after the onset of ischemia. This short therapeutic window for MK-801 suggests that NMDA receptors play only a transient role in reversible focal ischemia in rats.

scholarly journals The Role of Akt Signaling in Oxidative Stress Mediates NF-κB Activation in Mild Transient Focal Cerebral Ischemia

2008 ◽  
Vol 28 (12) ◽  
pp. 1917-1926 ◽  
Author(s):  
Yun Seon Song ◽  
Purnima Narasimhan ◽  
Gab Seok Kim ◽  
Joo Eun Jung ◽  
Eun-Hee Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Signaling Pathway ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Akt Signaling ◽  
Akt Inhibitor ◽  
Akt Phosphorylation ◽  
Transient Focal Cerebral Ischemia

Reactive oxygen species, derived from hypoxia and reoxygenation during transient focal cerebral ischemia (tFCI), are associated with the signaling pathway that leads to neuronal survival or death, depending on the severity and duration of the ischemic insult. The Akt survival signaling pathway is regulated by oxidative stress and is implicated in activation of nuclear factor-κB(NF-κB). Mild cerebral ischemia in mice was used to induce increased levels of Akt phosphorylation in the cortex and striatum. To clarify the role of Akt activation by NF-κB after tFCI, we injected the specific Akt inhibitor IV that inhibits Akt phosphorylation/activation. Inhibition of Akt phosphorylation induced decreases in sequential NF-κB signaling after 30 mins of tFCI at 1 h. Furthermore, the downstream survival signals of the Akt pathway were also decreased. Akt inhibitor IV increased ischemic infarct volume and apoptotic-related DNA fragmentation. Superoxide production in the ischemic brains of mice pretreated with the Akt inhibitor was higher than in vehicle-treated mice. In addition, those pretreated mice showed a reduction of approximately 33% in copper/zinc-superoxide dismutase expression. We propose that Akt signaling exerts its neuroprotective role by NF-κB activation in oxidative cerebral ischemia in mice.

Effects of ifenprodil, a polyamine site NMDA receptor antagonist, on reperfusion injury after transient focal cerebral ischemia

1997 ◽  
Vol 87 (6) ◽  
pp. 921-926 ◽  
Author(s):  
Aclan Doğgan ◽  
A. Muralikrishna Rao ◽  
Mustafa K. Başkaya ◽  
V. L. Raghavendra Rao ◽  
Jane Rastl ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Reperfusion Injury ◽  
Brain Edema ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Male Rats ◽  
Temporal Muscle ◽  
Transient Focal Cerebral Ischemia

✓ Polyamines and N-methyl-d-aspartate (NMDA) receptors are both thought to play an important role in secondary neuronal injury after cerebral ischemia. Ifenprodil, known as a noncompetitive inhibitor of polyamine sites at the NMDA receptor, was studied after transient focal cerebral ischemia occurred. Spontaneously hypertensive male rats, each weighing between 250 and 350 g, underwent 3 hours of tandem middle cerebral artery (MCA) and common carotid artery occlusion followed by reperfusion for a period of 3 hours or 21 hours. Intravenous ifenprodil (10 µg/kg/minute) or saline infusion was started immediately after the onset of MCA occlusion and continued throughout the ischemic period. Physiological parameters including blood pressure, blood gas levels, blood glucose, hemoglobin, and rectal and temporal muscle temperatures were monitored. Six rats from each group were evaluated at 6 hours postocclusion for brain water content, an indicator of brain edema, and Evans blue dye extravasation for blood-brain barrier breakdown. Infarct volume was also measured in six rats from each group at 6 and 24 hours postocclusion. Ifenprodil treatment significantly reduced brain edema (82.5 ± 0.4% vs. 83.5 ± 0.4%, p < 0.05) and infarct volume (132 ± 14 mm3 vs. 168 ± 25 mm3, p < 0.05) compared with saline treatment, with no alterations in temporal muscle (brain) or rectal (body) temperature (35.9 ± 0.4°C vs. 36.2 ± 0.2°C; 37.7 ± 0.4°C vs. 37.6 ± 0.6°C; not significant). These results demonstrate that ifenprodil has neuroprotective properties after ischemia/reperfusion injury in the absence of hypothermia. This indicates that antagonists selective for the polyamine site of the NMDA receptors may be a viable treatment option and helps to explain some of the pathophysiological mechanisms involved in secondary injury after transient focal cerebral ischemia has occurred.

scholarly journals The Neuroprotective Effect of the Novel Noncompetitive NMDA Antagonist, FR115427 in Focal Cerebral Ischemia in Rats

1995 ◽  
Vol 15 (2) ◽  
pp. 345-348 ◽  
Author(s):  
Kiyotaka Katsuta ◽  
Hajime Nakanishi ◽  
Kiyoharu Shirakawa ◽  
Keizo Yoshida ◽  
Kiyoshi Takagi ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Nmda Antagonist ◽  
Left Middle Cerebral Artery ◽  
The Novel ◽  
Mk 801 ◽  
Permanent Occlusion ◽  
Left Middle

The present study was carried out to compare the neuroprotective effect of the novel noncompetitive NMDA antagonist, FR115427, with that of (+)MK-801 in rat focal cerebral ischemia. Focal cerebral ischemia was produced by permanent occlusion of the left middle cerebral artery (MCA). Drugs were administered intraperitoneally immediately after ischemia and once a day for 6 successive days. FR115427 (10 mg/kg, i.p.) significantly improved neurologic deficit at 1 day after ischemia and reduced total infarct volume (54%) at 7 days after ischemia. Although FR115427 (10 mg/kg, s.c.) produced neuronal vacuolization similar to (+)MK-801, FR115427 did not produce adverse effects such as a loss of body weight, mortality, and hypothermia, in contrast to (+)MK-801. These results suggest that FR115427 may be useful in the treatment of stroke.

scholarly journals Dual Role of Fcγ Receptor in Transient Focal Cerebral Ischemia in Mice

Stroke ◽  
2004 ◽  
Vol 35 (4) ◽  
pp. 958-963 ◽  
Author(s):  
Miki Komine-Kobayashi ◽  
Nei Chou ◽  
Hideki Mochizuki ◽  
Atsuhito Nakao ◽  
Yoshikuni Mizuno ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Dual Role ◽  
Fcγ Receptor ◽  
Transient Focal Cerebral Ischemia

scholarly journals Neuroprotective Activity of Lavender Oil on Transient Focal Cerebral Ischemia in Mice

Molecules ◽  
2012 ◽  
Vol 17 (8) ◽  
pp. 9803-9817 ◽  
Author(s):  
Dong Wang ◽  
Xuan Yuan ◽  
Ting Liu ◽  
Liangliang Liu ◽  
Yanli Hu ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Activity ◽  
Lavender Oil ◽  
Transient Focal Cerebral Ischemia

scholarly journals Modulation by Nitric Oxide of Cerebral Neutrophil Accumulation after Transient Focal Ischemia in Rats

2000 ◽  
Vol 20 (5) ◽  
pp. 812-819 ◽  
Author(s):  
Sophie Batteur-Parmentier ◽  
Isabelle Margaill ◽  
Michel Plotkine
Keyword(s):  
Nitric Oxide ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neutrophil Infiltration ◽  
Focal Ischemia ◽  
Left Middle Cerebral Artery ◽  
No Production ◽  
Myeloperoxidase Activity ◽  
Transient Focal Ischemia

A beneficial role of nitric oxide (NO) after cerebral ischemia has been previously attributed to its vascular effects. Recent data indicate a regulatory role for NO in initial leukocyte-endothelial interactions in the cerebral microcirculation under basal and ischemic conditions. In this study, the authors tested the hypothesis that endogenous NO production during and/or after transient focal cerebral ischemia can also be neuroprotective by limiting the process of neutrophil infiltration and its deleterious consequences. Male Sprague-Dawley rats were subjected to 2 hours occlusion of the left middle cerebral artery and the left common carotid artery. The effect of NG-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg, intraperitoneally), an NO synthase inhibitor, was examined at 48 hours after ischemia on both infarct size and myeloperoxidase activity, an index of neutrophil infiltration. L-NAME given 5 minutes after the onset of ischemia increased the cortical infarct volume by 34% and increased cortical myeloperoxidase activity by 60%, whereas administration of L-NAME at 1, 7, and 22 hours of reperfusion had no effect. Such exacerbations of infarction and myeloperoxidase activity produced when L-NAME was given 5 minutes after the onset of ischemia were not observed in rats rendered neutropenic by vinblastine. These results suggest that after transient focal ischemia, early NO production exerts a neuroprotective effect by modulating neutrophil infiltration.

scholarly journals Expression of HSP70 in cerebral ischemia and neuroprotetive action of hypothermia and ketoprofen

2010 ◽  
Vol 68 (4) ◽  
pp. 592-596 ◽  
Author(s):  
Daniela Pretti da Cunha Tirapelli ◽  
Carlos Gilberto Carlotti Junior ◽  
João Pereira Leite ◽  
Luis Fernando Tirapelli ◽  
Benedicto Oscar Colli
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Hsp70 Expression ◽  
Tetrazolium Chloride ◽  
A Cell ◽  
Shock Proteins ◽  
H Protein

Heat shock proteins (HSPs) are molecular chaperones that bind to other proteins to shepherd them across membranes and direct them to specific locations within a cell. Several injurious stimuli can induce Hsp70 expression, including ischemia. This study aimed to investigate the pattern of expression of protein (immunohistochemistry) and gene (real-time PCR) Hsp70 in experimental focal cerebral ischemia in rats by occlusion of the middle cerebral artery for 1 hour and the role of neuroprotection with hypothermia (H) and ketoprofen (K). The infarct volume was measured using morphometric analysis defined by triphenyl tetrazolium chloride. It was observed increases in the protein (p=0.0001) and gene (p=0.0001) Hsp70 receptor in the ischemic areas that were reduced by H (protein and gene: p<0.05), K (protein: p<0.001), and H+K (protein: p<0.01 and gene: p<0.05). The Hsp70 increases in the ischemic area suggests that the Hsp70-mediated neuroexcitotoxicity plays an important role in cell death and that the neuroprotective effect of both, H and K are directly involved with the Hsp70.

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