scholarly journals Temporal Evolution of Regional Energy Metabolism following Focal Cerebral Ischemia in the Rat

1988 ◽  
Vol 8 (4) ◽  
pp. 462-473 ◽  
Author(s):  
J.-P. Nowicki ◽  
C. Assumel-Lurdin ◽  
D. Duverger ◽  
E. T. MacKenzie
Keyword(s):  
Energy Metabolism ◽  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Parietal Cortex ◽  
Cerebral Artery ◽  
Temporal Evolution ◽  
Focal Cerebral Ischemia ◽  
Biochemical Changes ◽  
Regional Energy ◽  
Cortical Regions

Focal cerebral ischemia in the rat was induced by occlusion of the left middle cerebral artery. The temporal evolution of regional energy metabolism was studied over the 14 days consequent to the induction of ischemia in the frontal, cingulate, parietal, and occipital cortices as well as in the striatum. Regional concentrations of adenosine triphosphate (ATP), phosphocreatine, and lactate and, in addition, glucose and the cerebral/plasma glucose ratio (C/P) were measured in the hemispheres both ipsilateral and contralateral to the occlusion. Two hours after middle cerebral artery occlusion, the biochemical changes were severe in the striatum and moderate in cortical regions. Later on (at 24 and 48 h), an overall aggravated metabolic status was noted while lactate declined and glucose markedly increased. These latter biochemical changes likely indicate a marked inhibition of the rate of glucose utilization. At 48 h, the energy reserves (ATP, phosphocreatine) of parietal cortex no longer equaled those of other cortical regions, but abruptly fell to the levels found in the striatum without any increase in lactate level. Finally, at 7 and 14 days, the levels of the various metabolites in most cortical regions returned toward control values, although signs of a depressed glucose metabolism remained. However, in both striatum and parietal cortex, ATP and phosphocreatine concentrations, although higher than those observed at 48 h, remained significantly decreased. Our present biochemical study permits the classification of these selected brain regions into three categories. First there are those that are outside the area of infarction: the frontal, cingulate, and occipital cortices. These regions show little temporal evolution of brain energy metabolism but, notwithstanding, they are regions in which glucose use would appear to be greatly depressed. Second is a region considered to be the focus of infarction: the striatum. The caudate-putamen is a region with early and profound metabolic disturbances with no final restitution. Last is the region of metabolic penumbra—the parietal cortex, in which there is a time-related exacerbation of the consequences of middle cerebral occlusion in the rat.

scholarly journals Spatial Cognitive Performance after Chronic Focal Cerebral Ischemia in Rats

1999 ◽  
Vol 19 (5) ◽  
pp. 483-494 ◽  
Author(s):  
Fumihiko Yonemori ◽  
Tohru Yamaguchi ◽  
Hideki Yamada ◽  
Akira Tamura
Keyword(s):  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Passive Avoidance ◽  
Cognitive Performance ◽  
Parietal Cortex ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Avoidance Task ◽  
Percent Time ◽  
Morris Maze

The authors investigated the impairment of spatial cognitive performance in rats with chronic focal cerebral ischemia using the Morris maze, and examined the correlation between this deficit and other behavioral changes, such as step-through latency in passive avoidance task and neurologic score, or pathologic changes. The authors focused on the relationship between the damaged brain region and the affected spatial learning behavior. In the Morris maze task at 8 weeks after the middle cerebral artery (MCA) occlusion, escape latency, swimming path length, and percent time spent in goal quadrant of MCA-occluded rats were impaired, which correlated with shrinkage of the cortex involving parietal cortex, but not caudate-putamen (CP). Middle cerebral artery-occluded rats were also impaired in the percent time spent in the outermost annulus and in turning ratio, which significantly correlated with shrinkage of CP, but not cortex. Middle cerebral artery-occluded rats showed two typical search patterns; one was almost the same as that of sham-operated and intact rats, and the other was round shaped and had less turning behavior. Both subgroups of MCA-occluded rats divided by turning ratio had significantly impaired spatial cognitive performance, which indicates that the changes of search pattern did not affect cognitive performance in the Morris maze. The neurologic deficits recovered gradually after MCA occlusion, which correlated with shrinkage of cortex and CP. The step-through latency in passive avoidance task of the MCA-occluded rats was impaired, but did not correlate with shrinkage of cortex or CP. These results suggest that the long-term spatial cognitive deficit of MCA-occluded rats is in part associated with damage to the cortex involving parietal cortex, and that the change of search strategies is associated with damage to CP. These findings support the idea that different brain regions contribute differently to cognitive performance, search strategies, avoidance task, and neurologic performance, and may be useful for estimating the related region of functional disorder in the clinical situation.

scholarly journals Relation of Apparent Diffusion Coefficient Changes and Metabolic Disturbances after 1 Hour of Focal Cerebral Ischemia and at Different Reperfusion Phases in Rats

2001 ◽  
Vol 21 (4) ◽  
pp. 430-439 ◽  
Author(s):  
Laszlo Olah ◽  
Stefan Wecker ◽  
Mathias Hoehn
Keyword(s):  
Energy Metabolism ◽  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Artery Occlusion ◽  
Atp Depletion ◽  
Apparent Diffusion ◽  
Tissue Acidosis ◽  
Cerebral Artery Occlusion ◽  
Energy Failure

Changes in apparent diffusion coefficients (ADC) were compared with alterations of adenosine triphosphate (ATP) concentration and pH in different phases of transient focal cerebral ischemia to study the ADC threshold for breakdown of energy metabolism and tissue acidosis during ischemia and reperfusion. Male Wistar rats underwent 1 hour of middle cerebral artery occlusion without recirculation (n = 3) or with 1 hour (n = 4) or 10 hours of reperfusion (n = 5) inside the magnet, using a remotely controlled thread occlusion model. ADC maps were calculated from diffusion-weighted images and normalized to the preischemic value to obtain relative ADC maps. Hemispheric lesion volume (HLV) was determined on the last relative ADC maps at different relative ADC thresholds and was compared to the HLV measured by ATP depletion and by tissue acidosis. The HLVs, defined by ATP depletion and tissue acidosis, were 26.0% ± 10.6% and 38.1% ± 6.5% at the end of ischemia, 3.3% ± 2.4% and 4.8% ± 3.5% after 1 hour of reperfusion, and 11.2% ± 4.7% and 10.9% ± 5.2% after 10 hours of recirculation, respectively. The relative ADC thresholds for energy failure were consistently approximately 77% of the control value in the three different groups. The threshold for tissue acidosis was higher at the end of ischemia (86% of control) but was similar to the results obtained for ATP depletion after 1 hour (78% of control) and 10 hours (76% of control) of recirculation. These results indicate that the described relative ADC threshold of approximately 77% of control provides a good estimate for the breakdown of energy metabolism not only during middle cerebral artery occlusion but also at the early phase of reperfusion, when recovery of energy metabolism is expected to occur, or some hours later, when development of secondary energy failure was described.

scholarly journals L-Arginine Does Not Improve Cortical Perfusion or Histopathological Outcome in Spontaneously Hypertensive Rats Subjected to Distal Middle Cerebral Artery Photothrombotic Occlusion

1996 ◽  
Vol 16 (4) ◽  
pp. 612-622 ◽  
Author(s):  
Ricardo Prado ◽  
Brant D. Watson ◽  
Weizhao Zhao ◽  
Hiroshi Yao ◽  
Raul Busto ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Spontaneously Hypertensive Rats ◽  
Therapeutic Potential ◽  
Focal Cerebral Ischemia ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Tissue Reactions ◽  
Distal Middle Cerebral Artery

The potential of nitric oxide (NO) to influence positively or negatively the outcome of mechanically induced focal cerebral ischemia is still controversial. Recent evidence suggests that NO of vascular origin, whether synthesized from exogenously administered L-arginine (L-Arg) or from NO donor compounds, is beneficial but that of neuronal origin is not. However, the therapeutic potential of NO to ameliorate stroke induced by arterial thrombosis has not been reported. We assessed the therapeutic effect of L-Arg administration in spontaneously hypertensive rats (SHR) subjected to permanent photothrombotic occlusion of the distal middle cerebral artery (dMCA). The ipsilateral carotid artery was left unligated to enhance L-Arg delivery into the putative penumbral region. Local CBF (LCBF) was assessed at 30 min by the [14C]iodoantipyrine technique (n = 9), while histological infarct volumes and index of peripheral ischemic cell change were determined at 3 days (n = 7). Rats (n = 9) given 300 mg/kg L-Arg at 18 and 3 h before photothrombotic dMCA occlusion and at 5 min afterward displayed no significant differences in LCBF compared with animals (n = 8) injected with water (the carrier vehicle) and similarly irradiated. Infarct volumes were also similar, being 37.0 ± 9.7 mm3 (SD) in the vehicle-treated and 49.1 ± 17.2 mm3 (SD) in the L-Arg-treated groups (both n = 7), as were assessments of ischemic neuronal density in the penumbra. In contrast, L-Arg administered intravenously in a dose of 300 mg/kg to nonischemic SHR (n = 5) increased cortical CBF by ∼75% during a 70-min observation period. We conclude that thrombotic processes superimposed upon cerebral ischemia may facilitate tissue reactions that offset the potentially beneficial effect of L-Arg, and this caveat must be considered when proposing L-Arg for clinical treatment of focal thrombotic stroke.

Reperfusion Decreases Myogenic Reactivity and Alters Middle Cerebral Artery Function After Focal Cerebral Ischemia in Rats

Stroke ◽  
1997 ◽  
Vol 28 (1) ◽  
pp. 176-180 ◽  
Author(s):  
Marilyn J. Cipolla ◽  
Anthony L. McCall ◽  
Nikola Lessov ◽  
John M. Porter
Keyword(s):  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia

scholarly journals Inhibition of MicroRNA-383 Ameliorates Injury After Focal Cerebral Ischemia via Targeting PPARγ

2016 ◽  
Vol 39 (4) ◽  
pp. 1339-1346 ◽  
Author(s):  
Lichun Pei ◽  
Songyan Meng ◽  
Weigang Yu ◽  
Qiujun Wang ◽  
Fangfang Song ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Protein Level ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Luciferase Assay ◽  
Cerebral Artery Occlusion

Background: Peroxisome proliferator-activated receptor gamma (PPARγ) plays a critical role in protecting against distinct brain damages, including ischemia. Our previous data have shown that the protein level of PPARγ is increased in the cortex after middle cerebral artery occlusion (MCAO); PPARγ up-regulation contributes to PPARγ activation and is effective in reducing ischemic damage to brain. However, the regulatory mechanism of PPARγ after focal cerebral ischemia in rats is still unclear. In this study, we evaluated the effect of microRNA on PPARγ in rats subjected to MCAO. Methods: Focal cerebral ischemia was established by surgical middle cerebral artery occlusion; the protein level of PPARγ was detected by Western blotting; the level of microRNA-383 (miR-383) was quantified by real-time PCR; the neurological outcomes were defined by infarct volume and neurological deficits. Luciferase assay was used to identify the luciferase activities of PPARγ and miR-383. Results: We showed here that miR-383 level was down-regulated in the ischemic hemisphere of rats 24h after MCAO. Overexpression of miR-383 by miR-383 agomir increased infarct volume and aggravated neurological damage. Administration of miR-383 antagomir had the opposite effects. Furthermore, we found that PPARγ protein was down-regulated by miR-383 overexpression, and up-regulated by miR-383 inhibition both in rat model of MCAO and in primary culture cells. Finally, we found that miR-383 suppressed the luciferase activity of the vector carrying the 3'UTR of PPARγ, whereas mutation of the binding sites relived the repressive effect of miR-383. Conclusion: Our study demonstrated that miR-383 may play a key role in focal cerebral ischemia by regulating PPARγ expression at the post-transcriptional level, and miR-383 may be a potential therapeutic target for stroke.

scholarly journals Neuroprotective Effect of the AMPA Receptor Antagonist LY-293558 in Focal Cerebral Ischemia in the Cat

1994 ◽  
Vol 14 (3) ◽  
pp. 466-471 ◽  
Author(s):  
R. Bullock ◽  
D. I. Graham ◽  
S. Swanson ◽  
J. McCulloch
Keyword(s):  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Receptor Antagonist ◽  
Ampa Receptor ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Ischemic Damage ◽  
Physiological Variables ◽  
Ampa Receptor Antagonist

The effects of the glutamate α-amino-3-hydroxy 5-methyl-4-isoxazole propionate (AMPA) receptor antagonist LY-293558 in reducing ischemic brain damage have been assessed in halothane-anesthetized cats. Focal cerebral ischemia was produced by permanent occlusion of one middle cerebral artery, and the animals were killed 6 h later. The amount of early irreversible ischemic damage was assessed at 16 predetermined stereotactic planes by an observer blinded to treatment paradigm employed. Treatment with LY-293558 (15 mg/kg i.v., plus infusion of 7 mg/kg/h) initiated 30 min prior to middle cerebral artery occlusion reduced significantly (p < 0.02) the volume of ischemic damage (from 3,423 ± 212 mm3 of the cerebral hemisphere in vehicle-treated cats to 2,822 ± 569 mm3 in LY-293558-treated cats). The present data demonstrate that an AMPA receptor antagonist can reduce focal ischemic damage in a gyrencephalic species in which key physiological variables have been controlled and monitored throughout the postischemic period. These data provide additional support for the clinical evaluation of AMPA receptor antagonists in focal cerebral ischemia in humans.

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