Core and Penumbral Nitric Oxide Synthase Activity During Cerebral Ischemia and Reperfusion

Abstract

Background and Purpose-The present studies examined the hypothesis that the distribution of cerebral injury after a focal ischemic insult is associated with the regional distribution of nitric oxide synthase (NOS) activity. Methods-Based on previous studies that certain anatomically well-defined areas are prone to become either core or penumbra after middle cerebral artery occlusion (MCAO), we measured NOS activity in these areas from the right and left hemispheres in a spontaneously hypertensive rat filament model. Four groups were studied: (1) controls (immediate decapitation); (2) 1.5 hours of MCAO with no reperfusion (R0); (3) 1.5 hours of MCAO with 0.5 hour of reperfusion (R0.5); and (4) 1.5 hours of MCAO with 24 hours of reperfusion (R24). Three groups of corresponding isoflurane sham controls were also included: 1.5 (S1.5) or 2 (S2.0) hours of anesthesia and 1.5 hours of anesthesiaϩ24 hours of observation (S24). Results-Control core NOS activity for combined right and left hemispheres was 129% greater than penumbral NOS activity (PϽ0.05). Combined core NOS activity was also greater (PϽ0.05) in the three sham groups: 208%, 122%, and 161%, respectively. In the three MCAO groups, ischemic and nonischemic core NOS remained higher than penumbral regions (PϽ0.05). However, NOS activity was lower in the ischemic than in the nonischemic core in all three groups: R0 (29% lower), R0.5 (48%), and R24 (86%) (PϽ0.05). Addition of cofactors (10 mol/L tetrahydrobiopterin, 3 mol/L flavin adenine dinucleotide, and 3 mol/L flavin mononucleotide) increased NOS activity in all groups and lessened the decrease in ischemic core and penumbral NOS. Conclusions-Greater NOS activity in core regions could explain in part the increased vulnerability of that region to ischemia and could theoretically contribute to the progression of the infarct over time. The data also suggest that NOS activity during ischemia and reperfusion could be influenced by the availability of cofactors.

Activation of Epsilon Protein Kinase C-Mediated Anti-Apoptosis Is Involved in Rapid Tolerance Induced by Electroacupuncture Pretreatment Through Cannabinoid Receptor Type 1

“…Ischemic core and penumbra were dissected according to well-established protocols in rodent models of unilateral proximal MCAO. 25,26 …”

Efficacy of phosphocreatine pre-administration on XIAP and Smac in ischemic penumbra of rats with focal cerebral ischemia reperfusion injury

“…The infarcted core area and ischemic penumbra were defined using the same microscope, as previously described 13 .The tissue was then stained with hematoxylin and eosin (HE).…”

“…Using a previously described method 13 , the coronal segments were then sliced at sites, which were 3 mm and 9 mm away from the frontal lobe front. The brain tissue (6 mm in thickness) within the above segment was then cut open along the line 2 mm away from the sagittal suture.…”

“…The results showed that although PCr can increase the expression of XIAP and reduce the expression of Smac in infarcted core region to a certain extent, the striatum was the tissue firstly involved in the infarcted core area; so PCr could not reverse serious injury of the striatum and could only reduce the injury in partial parietal cortex and frontal cortex. According to the positioning method of the cerebral ischemic penumbra in rats 13 and the HE staining results, these areas made up the ischemic penumbra. In addition, TUNEL staining results showed that PCr could not reduce the number of apoptotic cells in the infarcted core region.…”

Atividade simpática, parassimpática e metabólica influenciadas pelo comportamento da distribuição do suporte de peso em pé adquirido na condição de hemiparesia crônica

“…O NO está envolvido no processo de morte celular durante eventos isquêmicos (66) . As concentrações de nitrato (metabólito do NO) encontram-se elevadas no líquido cefalorraquiano de pacientes vítimas de AVC do tipo isquêmico (67) .…”