The Correlation between Electrophysiological Parameters /EEG, DC and Tissue Available O2/ and Regional Metabolites /pH, ATP, Glucose, NADH, K/ after 45 Min MCA Occlusion and 3 Hours Recirculation in Cats

Introduction: Cognition and memory deficits are common sequelae following middle cerebral artery (MCA) stroke, one of the most common strokes in humans. However MCA stroke does not compromise the structural integrity of the hippocampus, which is highly involved in memory function, because the MCA does not supply blood flow to the hippocampus. We previously reported on the acute effect of MCA stroke, where we observed increased hippocampal activity and cortico-hippocampal communication. Here we investigate chronic changes to local oscillations and cortico-hippocampal communication following MCA occlusion in rats two weeks and one month following stroke. Hypothesis: Cortical stroke affects remote brain regions, disrupting hippocampal function and cortico-hippocampal communication. Methods: We subjected male rats (n=28) to distal MCA occlusion compared to controls (n=19). We recorded local field potentials simultaneously from cortex and hippocampus two weeks and one month following stroke using 16-site linear electrode arrays under urethane anesthesia. We analyzed signal power, brain state, CFC, and sharp wave SPW-Rs to assess hippocampal function and cortico-hippocampal communication. Results: Our results show disruptions to local oscillations; lowered delta (1-3 Hz) signal power in the cortex and hippocampus, increased signal power in gamma (30-60 Hz) and high gamma (60-200 Hz) in cortex and hippocampus. Theta/delta brain state is disrupted, and SPW-Rs increase in power at two weeks, before returning to baseline levels at one month. Communication is also disrupted; Theta-gamma coupling, a measure of information being communicated between regions, breaks down after stroke. Conclusions: These results suggest that chronic stroke causes significant changes to hippocampal function, which can be characterized by these electrophysiological biomarkers, establishing putative targets for targeted stimulation therapies.

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Abstract 3438: Intracranial Arterial Occlusion and Extent of Hypoattenuation on CT Angiography Source Images may Modify the Benefit of Thrombolysis

Stroke ◽

10.1161/str.43.suppl_1.a3438 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Imanuel Dzialowski ◽

Volker Puetz ◽

Jasmin Renger ◽

Andrei Khomenko ◽

Ulf Bodechtel ◽

...

Keyword(s):

Functional Outcome ◽

Ct Angiography ◽

Time Window ◽

Brain Infarction ◽

Randomized Study ◽

Arterial Occlusion ◽

Extended Time ◽

Anterior Circulation ◽

Nihss Score ◽

Mca Occlusion

Background: CT angiography source images (CTASI) improve diagnostic accuracy for ischemic brain infarction compared to non-contrast CT (NCCT). We studied whether CTASI alone or combined with the CTA occlusion status may improve patient selection for thrombolysis in an extended time window. Methods: We prospectively observed patients presenting with anterior circulation ischemic stroke within 12 hours from symptom onset and an NIHSS score ≥ 3. All patients underwent cranial NCCT and CTA. Patients were treated with intravenous and/or intra-arterial thrombolysis at the discretion of the treating stroke neurologist and neuroloradiologist. We determined intracranial occlusion status and applied the Alberta Stroke Program Early CT Score (ASPECTS) to CTASI. Primary clinical outcome measure was independent outcome at 3 months, defined as mRS scores 0-2. We calculated unadjusted risk ratios to assess the effect of thrombolysis on functional outcome in patients with: 1) minor ischemic changes on CTASI (CTASI-ASPECTS >5) and 2) patients with minor ischemic changes on CTASI and middle cerebral artery (MCA) occlusion. Results: We enrolled 102 patients with a mean age of 71 +/- 12 years, median onset-to-CTA time of 112,5 (range 37-898) min, a median NIHSS score of 9.5 (3-39), and a median CTASI-ASPECTS of 8. Sixty-two patients (61%) received any thrombolysis (56 IV, 5 IV/IA, 1 IA). MCA occlusion was present in 57 patients (56%), 80/101 (80%) assessable patients had a CTASI-ASPECTS >5 and 37/101 (37%) patients had a CTASI-ASPECTS >5 in the presence of a MCA occlusion. At 3 months, 52 (51%) patients had an independent functional outcome. When patients with CTA-SI ASPECTS > 5 received thrombolysis, 30/46 (65%) achieved an independent functional outcome, whereas 20/35 (57%) without thrombolysis were functionally independent (RR 1.1, CI 95 0.8-1.6). In patients with CTASI-ASPECTS > 5 and additional MCA-occlusion, 13/24 (54%) with thrombolysis and 3/13 (23%) without thrombolysis achieved an independent functional outcome (RR 2.3, CI 95 0.8-6.8). Conclusion: In our non-randomized study, the extent of CTASI hypoattenuation alone did not identify patients benefiting from thrombolysis. In the presence of an MCA-occlusion, however, CTASI might identify patients with benefit from thrombolysis in an extended time window.

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Cell Type Specific Upregulation of Vascular Endothelial Growth Factor in an MCA-occlusion Model of Cerebral Infarct

Journal of Neuropathology & Experimental Neurology ◽

10.1097/00005072-199906000-00010 ◽

1999 ◽

Vol 58 (6) ◽

pp. 654-666 ◽

Cited By ~ 183

Author(s):

Karl H. Plate ◽

Heike Beck ◽

Simone Danner ◽

Peter R. Allegrini ◽

Christoph Wiessner

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Cerebral Infarct ◽

Vascular Endothelial ◽

Cell Type ◽

Mca Occlusion ◽

Occlusion Model ◽

Cell Type Specific ◽

Endothelial Growth Factor

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Decompressive craniectomy in a rat model of “malignant” cerebral hemispheric stroke: experimental support for an aggressive therapeutic approach

Journal of Neurosurgery ◽

10.3171/jns.1996.85.5.0853 ◽

1996 ◽

Vol 85 (5) ◽

pp. 853-859 ◽

Cited By ~ 126

Author(s):

Arnd Doerfler ◽

Michael Forsting ◽

Wolfgang Reith ◽

Christian Staff ◽

Sabine Heiland ◽

...

Keyword(s):

Cerebral Ischemia ◽

Decompressive Craniectomy ◽

Control Group ◽

Acute Ischemia ◽

Vessel Occlusion ◽

Content Type ◽

Time Points ◽

Infarction Size ◽

Mca Occlusion ◽

Fine Print

✓ Acute ischemia in the complete territory of the carotid artery may lead to massive cerebral edema with raised intracranial pressure and progression to coma and death due to uncal, cingulate, or tonsillar herniation. Although clinical data suggest that patients benefit from undergoing decompressive surgery for acute ischemia, little data about the effect of this procedure on experimental ischemia are available. In this article the authors present results of an experimental study on the effects of decompressive craniectomy performed at various time points after endovascular middle cerebral artery (MCA) occlusion in rats. Focal cerebral ischemia was induced in 68 rats using an endovascular occlusion technique focused on the MCA. Decompressive cranioectomy was performed in 48 animals (in groups of 12 rats each) 4, 12, 24, or 36 hours after vessel occlusion. Twenty animals (control group) were not treated by decompressive craniectomy. The authors used the infarct volume and neurological performance at Day 7 as study endpoints. Although the mortality rate in the untreated group was 35%, none of the animals treated by decompressive craniectomy died (mortality 0%). Neurological behavior was significantly better in all animals treated by decompressive craniectomy, regardless of whether they were treated early or late. Neurological behavior and infarction size were significantly better in animals treated very early by decompressive craniectomy (4 hours) after endovascular MCA occlusion (p < 0.01); surgery performed at later time points did not significantly reduce infarction size. The results suggest that use of decompressive craniectomy in treating cerebral ischemia reduces mortality and significantly improves outcome. If performed early after vessel occlusion, it also significantly reduces infarction size. By performing decompressive craniectomy neurosurgeons will play a major role in the management of stroke patients.

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Cerebrovascular Hemodynamics and Ischemic Tolerance: Lipopolysaccharide-Induced Resistance to Focal Cerebral Ischemia is not Due to Changes in Severity of the Initial Ischemic Insult, but is Associated with Preservation of Microvascular Perfusion

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-199906000-00004 ◽

1999 ◽

Vol 19 (6) ◽

pp. 616-623 ◽

Cited By ~ 81

Author(s):

Deborah A. Dawson ◽

Kazuhide Furuya ◽

Jun Gotoh ◽

Yasuaki Nakao ◽

John M. Hallenbeck

Keyword(s):

Focal Cerebral Ischemia ◽

Infarct Volume ◽

Ischemic Injury ◽

Ischemic Tolerance ◽

Microvascular Perfusion ◽

Saline Control ◽

Ischemic Insult ◽

Mca Occlusion ◽

Induced Tolerance ◽

Tissue Sparing

Lipopolysaccharide (LPS), administered 72 hours before middle cerebral artery (MCA) occlusion, confers significant protection against ischemic injury. For example, in the present study, LPS (0.9 mg/kg intravenously) induced a 31% reduction in infarct volume (compared with saline control) assessed 24 hours after permanent MCA occlusion. To determine whether LPS induces true tolerance to ischemia, or merely attenuates initial ischemic severity by augmenting collateral blood flow, local CBF was measured autoradiographically 15 minutes after MCA occlusion. Local CBF did not differ significantly between LPS- and saline-pretreated rats (e.g., 34 ± 10 and 29 ± 15 mL·100 g−1·min−1 for saline and LPS pretreatment in a representative region of ischemic cortex), indicating that the neuroprotective action of LPS is not attributable to an immediate reduction in the degree of ischemia induced by MCA occlusion, and that LPS does indeed induce a state of ischemic tolerance. In contrast to the similarity of the initial ischemic insult between tolerant (LPS-pretreated) and nontolerant (saline-pretreated) rats, microvascular perfusion assessed either 4 hours or 24 hours after MCA occlusion was preserved at significantly higher levels in the LPS-pretreated rats than in controls. Furthermore, the regions of preserved perfusion in tolerant animals were associated with regions of tissue sparing. These results suggest that LPS-induced tolerance to focal ischemia is at least partly dependent on the active maintenance of microvascular patency and hence the prevention of secondary ischemic injury.

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Limiting Ischemic Injury by Inhibition of Excitatory Amino Acid Release

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1993.11 ◽

1993 ◽

Vol 13 (1) ◽

pp. 88-97 ◽

Cited By ~ 122

Author(s):

Steven H. Graham ◽

Jun Chen ◽

Frank R. Sharp ◽

Roger P. Simon

Keyword(s):

Excitatory Amino Acid ◽

Glutamate Release ◽

Ischemic Injury ◽

Retrosplenial Cortex ◽

Mca Occlusion ◽

Alternative Approach ◽

Proximal Middle Cerebral Artery ◽

Human Use ◽

Unacceptable Toxicity

Excitatory amino acids (EAAs) are important mediators of ischemic injury in stroke. N-Methyl-d-aspartate (NMDA) receptor antagonists have been shown to be very effective neuroprotective agents in animal models of stroke, but may have unacceptable toxicity for human use. An alternative approach is to inhibit the release of EAAs during stroke. BW1003C87 [5-(2,3,5-trichlorophenyl)-2,4-diaminopyrimidine], a drug that inhibits veratrine-induced release of the EAA glutamate in vitro, was tested in a rat model of proximal middle cerebral artery (MCA) occlusion. BW1003C87 significantly decreased ischemia-induced glutamate release in brain when given either 5 min before or 15 min following permanent MCA occlusion. Pretreated and posttreated rats had smaller infarct volumes and preserved glucose metabolism in the ischemic cortex at 24 h after MCA occlusion. BW1003C87 did not induce heat shock protein in the cingulate or retrosplenial cortex, suggesting that it does not injure neurons in these regions as do NMDA antagonists. These results demonstrate that drugs that inhibit glutamate release in ischemia may be nontoxic and show promise for the treatment of stroke.

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Acute Middle Cerebral Artery Occlusion: Experience with Volume Expansion Therapy

Neurosurgery ◽

10.1227/00006123-198604000-00001 ◽

1986 ◽

Vol 18 (4) ◽

pp. 397-401 ◽

Cited By ~ 12

Author(s):

Bruce I. Tranmer ◽

Cordell E. Gross ◽

Ted S. Keller ◽

Glenn W. Kindt

Keyword(s):

Cardiac Output ◽

Middle Cerebral Artery ◽

Cerebral Artery ◽

Volume Expansion ◽

Artery Occlusion ◽

Neurological Deficits ◽

Life Styles ◽

Arterial Blood ◽

Mca Occlusion ◽

The Mean

Abstract Five consecutive patients with acute neurological deficits after middle cerebral artery (MCA) occlusion were given emergency treatment with colloidal volume expansion. In each case, the diagnosis was confirmed promptly by computed tomography and cerebral angiography. Aggressive volume expansion therapy was started 2 to 18 hours (mean, 11 hr) after the onset of the neurological deficit. The mean colloidal volume used was 920 ml/day for an average of 4 days. During volume expansion, the mean cardiac output increased 57% from 4.6 + 0.6 to 7.2 + 1.9 litres/min (P < 0.05). The mean hematocrit decreased 19% from 46 + 3% to 37 + 4% (P < 0.01). The mean arterial blood pressure remained stable, and the pulmonary artery wedge pressure was maintained at < 15 mm Hg. Three patients improved dramatically with volume expansion therapy and have returned to their previous life-styles. Two patients made partial recoveries and manage at home with nursing care. The three patients who improved dramatically were young (aged <34) and, when compared to the older patients, they had greater increases in cardiac output (67% vs. 19%). No major complications or deaths were attributed to the volume expansion therapy. We propose that intravascular volume expansion and its concomitant augmentation of the cardiovascular dynamics may be effective in the treatment of acute neurological deficits after acute MCA occlusion.

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Cytosolic Redistribution of Cytochrome C after Transient Focal Cerebral Ischemia in Rats

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-199811000-00010 ◽

1998 ◽

Vol 18 (11) ◽

pp. 1239-1247 ◽

Cited By ~ 228

Author(s):

Miki Fujimura ◽

Yuiko Morita-Fujimura ◽

Kensuke Murakami ◽

Makoto Kawase ◽

Pak H. Chan

Keyword(s):

Cerebral Ischemia ◽

Cytochrome C ◽

Western Blot ◽

Blot Analysis ◽

Western Blot Analysis ◽

Focal Cerebral Ischemia ◽

Cytochrome C Release ◽

Ischemic Lesion ◽

Mca Occlusion ◽

Transient Focal Cerebral Ischemia

Recent in vitro cell-free studies have shown that cytochrome c release from mitochondria is a critical step in the apoptotic process. The present study examined the expression of cytochrome c protein after transient focal cerebral ischemia in rats, in which apoptosis was assumed to contribute to the expansion of the ischemic lesion. In situ labeling of DNA breaks in frozen sections after 90 minutes of middle cerebral artery (MCA) occlusion showed a significant number of striatal and cortical neurons, which were maximized at 24 hours after ischemia, exhibiting chromatin condensation, nuclear segmentation, and apoptotic bodies. Cytosolic localization of cytochrome c was detected immunohistochemically in the ischemic area as early as 4 hours after 90 minutes of MCA occlusion. Western blot analysis of the cytosolic fraction revealed a strong single 15-kDa band, characteristic of cytochrome c, only in the samples from the ischemic hemisphere. Western blot analysis of the mitochondrial fraction showed a significant amount of mitochondrial cytochrome c in nonischemic brain, which was decreased in ischemic brain 24 hours after ischemia. These results provide the first evidence that cytochrome c is being released from mitochondria to the cytosol after transient focal ischemia. Although further evaluation is necessary to elucidate its correlation with DNA fragmentation, our results suggest the possibility that cytochrome c release may play a role in DNA-damaged neuronal cell death after transient focal cerebral ischemia in rats.

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