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Experimental Focal Cerebral Ischemia: - Pathophysiology, metabolism and pharmacology of the ischemic penumbra

Publikation: Bog/antologi/afhandling/rapportBog

Standard

Experimental Focal Cerebral Ischemia : - Pathophysiology, metabolism and pharmacology of the ischemic penumbra. / Christensen, Thomas.

2007. 56 s.

Publikation: Bog/antologi/afhandling/rapportBog

Harvard

Christensen, T 2007, Experimental Focal Cerebral Ischemia: - Pathophysiology, metabolism and pharmacology of the ischemic penumbra.

APA

Christensen, T. (2007). Experimental Focal Cerebral Ischemia: - Pathophysiology, metabolism and pharmacology of the ischemic penumbra.

Vancouver

Christensen T. Experimental Focal Cerebral Ischemia: - Pathophysiology, metabolism and pharmacology of the ischemic penumbra. 2007. 56 s.

Author

Christensen, Thomas. / Experimental Focal Cerebral Ischemia : - Pathophysiology, metabolism and pharmacology of the ischemic penumbra. 2007. 56 s.

Bibtex

@book{a84b1aedcfa6482fa14ca71d6a7fba5d,
title = "Experimental Focal Cerebral Ischemia: - Pathophysiology, metabolism and pharmacology of the ischemic penumbra",
abstract = "Focal cerebral ischemia due to occlusion of a major cerebral artery is the cause of ischemic stroke which is a major reason of mortality, morbidity and disability in the populations of the developed countries. In the seven studies summarized in the thesis focal ischemia in rats induced by occlusion of the middle cerebral artery (MCAO) was used as an experimental model of ischemic stroke. MCAO produces an acute lesion consisting of an ischemic core or focus with severely reduced blood flow surrounded by a borderzone or ischemic penumbra with less pronounced blood flow reduction. Cells in the ischemic focus are irreversibly damaged after only 15-30 minutes of ischemia. In contrast, cells in the penumbra may – although threatened and functionally impaired – remain viable for several hours following arterial occlusion but will eventually also succumb if ischemia persists. In this way the initially viable tissue in the penumbra is recruited in the infarction process leading to a progressive growth of the infarct. The penumbra hence constitutes an important target for pharmacological treatment because of the existence of a therapeutic time window during which treatment with neuroprotective compounds may prevent recruitment of penumbra to infarct resulting in mitigation of the final ischemic brain damage. The pathogenetic mechanisms involved in ischemic cell death in the penumbra encompass excitotoxic mechanisms mediated by activation of ionotropic glutamate receptors, loss of cellular calcium homeostasis and accelerated generation of damaging free oxygen radiacals. The overall aim of the studies was to elucidate the pathogenetic and pathophysiological mechanisms involved in recruitment of the penumbra in the acute phase of focal ischemia. In the three first studies, it was specifically addressed how the glutamate receptor antagonsists MK-801 and NBQX influence expression of Fos protein, a product of the immediate-early gene c-fos, and changes of general protein synthesis and glucose consumption in the penumbra in the acute phase following MCAO. The effect of treatment with ketobemidone, an opioid receptor agonist and weak NMDA glutamate receptor antagonist, upon protein synthesis and glucose metabolism in the penumbra and infarct volume was investigated in a fourth study. In the fifth study, transient periinfarct depolarizations were recorded and the effect of treatment with the free radical scavenger α-PBN on the periinfarct depolarizations and infarct volume was investigated. In study number six, the activity of the mitochondrial electron transport complexes I, II and IV was evaluated histochemically during reperfusion after MCAO in order to assess the possible role of mitochondrial dysfunction in focal ischemic brain damage. Finally, the effect on infarct volume one week after MCAO of treatment with Pinokalant, a new broad-spectrum cation channel blocker, was examined in the seventh study. The results of these studies are presented and discussed in relation to the current knowledge of the pathogenetic and pathophysological mechanisms involved in the acute phase of the infarction process.",
author = "Thomas Christensen",
note = "Doktordisputats (dr. med.)",
year = "2007",
language = "English",
isbn = "978-87-992138-0-1",

}

RIS

TY - BOOK

T1 - Experimental Focal Cerebral Ischemia

T2 - - Pathophysiology, metabolism and pharmacology of the ischemic penumbra

AU - Christensen, Thomas

N1 - Doktordisputats (dr. med.)

PY - 2007

Y1 - 2007

N2 - Focal cerebral ischemia due to occlusion of a major cerebral artery is the cause of ischemic stroke which is a major reason of mortality, morbidity and disability in the populations of the developed countries. In the seven studies summarized in the thesis focal ischemia in rats induced by occlusion of the middle cerebral artery (MCAO) was used as an experimental model of ischemic stroke. MCAO produces an acute lesion consisting of an ischemic core or focus with severely reduced blood flow surrounded by a borderzone or ischemic penumbra with less pronounced blood flow reduction. Cells in the ischemic focus are irreversibly damaged after only 15-30 minutes of ischemia. In contrast, cells in the penumbra may – although threatened and functionally impaired – remain viable for several hours following arterial occlusion but will eventually also succumb if ischemia persists. In this way the initially viable tissue in the penumbra is recruited in the infarction process leading to a progressive growth of the infarct. The penumbra hence constitutes an important target for pharmacological treatment because of the existence of a therapeutic time window during which treatment with neuroprotective compounds may prevent recruitment of penumbra to infarct resulting in mitigation of the final ischemic brain damage. The pathogenetic mechanisms involved in ischemic cell death in the penumbra encompass excitotoxic mechanisms mediated by activation of ionotropic glutamate receptors, loss of cellular calcium homeostasis and accelerated generation of damaging free oxygen radiacals. The overall aim of the studies was to elucidate the pathogenetic and pathophysiological mechanisms involved in recruitment of the penumbra in the acute phase of focal ischemia. In the three first studies, it was specifically addressed how the glutamate receptor antagonsists MK-801 and NBQX influence expression of Fos protein, a product of the immediate-early gene c-fos, and changes of general protein synthesis and glucose consumption in the penumbra in the acute phase following MCAO. The effect of treatment with ketobemidone, an opioid receptor agonist and weak NMDA glutamate receptor antagonist, upon protein synthesis and glucose metabolism in the penumbra and infarct volume was investigated in a fourth study. In the fifth study, transient periinfarct depolarizations were recorded and the effect of treatment with the free radical scavenger α-PBN on the periinfarct depolarizations and infarct volume was investigated. In study number six, the activity of the mitochondrial electron transport complexes I, II and IV was evaluated histochemically during reperfusion after MCAO in order to assess the possible role of mitochondrial dysfunction in focal ischemic brain damage. Finally, the effect on infarct volume one week after MCAO of treatment with Pinokalant, a new broad-spectrum cation channel blocker, was examined in the seventh study. The results of these studies are presented and discussed in relation to the current knowledge of the pathogenetic and pathophysological mechanisms involved in the acute phase of the infarction process.

AB - Focal cerebral ischemia due to occlusion of a major cerebral artery is the cause of ischemic stroke which is a major reason of mortality, morbidity and disability in the populations of the developed countries. In the seven studies summarized in the thesis focal ischemia in rats induced by occlusion of the middle cerebral artery (MCAO) was used as an experimental model of ischemic stroke. MCAO produces an acute lesion consisting of an ischemic core or focus with severely reduced blood flow surrounded by a borderzone or ischemic penumbra with less pronounced blood flow reduction. Cells in the ischemic focus are irreversibly damaged after only 15-30 minutes of ischemia. In contrast, cells in the penumbra may – although threatened and functionally impaired – remain viable for several hours following arterial occlusion but will eventually also succumb if ischemia persists. In this way the initially viable tissue in the penumbra is recruited in the infarction process leading to a progressive growth of the infarct. The penumbra hence constitutes an important target for pharmacological treatment because of the existence of a therapeutic time window during which treatment with neuroprotective compounds may prevent recruitment of penumbra to infarct resulting in mitigation of the final ischemic brain damage. The pathogenetic mechanisms involved in ischemic cell death in the penumbra encompass excitotoxic mechanisms mediated by activation of ionotropic glutamate receptors, loss of cellular calcium homeostasis and accelerated generation of damaging free oxygen radiacals. The overall aim of the studies was to elucidate the pathogenetic and pathophysiological mechanisms involved in recruitment of the penumbra in the acute phase of focal ischemia. In the three first studies, it was specifically addressed how the glutamate receptor antagonsists MK-801 and NBQX influence expression of Fos protein, a product of the immediate-early gene c-fos, and changes of general protein synthesis and glucose consumption in the penumbra in the acute phase following MCAO. The effect of treatment with ketobemidone, an opioid receptor agonist and weak NMDA glutamate receptor antagonist, upon protein synthesis and glucose metabolism in the penumbra and infarct volume was investigated in a fourth study. In the fifth study, transient periinfarct depolarizations were recorded and the effect of treatment with the free radical scavenger α-PBN on the periinfarct depolarizations and infarct volume was investigated. In study number six, the activity of the mitochondrial electron transport complexes I, II and IV was evaluated histochemically during reperfusion after MCAO in order to assess the possible role of mitochondrial dysfunction in focal ischemic brain damage. Finally, the effect on infarct volume one week after MCAO of treatment with Pinokalant, a new broad-spectrum cation channel blocker, was examined in the seventh study. The results of these studies are presented and discussed in relation to the current knowledge of the pathogenetic and pathophysological mechanisms involved in the acute phase of the infarction process.

M3 - Book

SN - 978-87-992138-0-1

BT - Experimental Focal Cerebral Ischemia

ER -

ID: 107825835