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Molecular mechanisms of brain ischemia and its protection

Uchino, Hiroyuki LU ; Chijiiwa, Miyuki; Ogihara, Yukihiko and Elmer, Eskil LU (2015) In Neuroanesthesia and Cerebrospinal Protection p.39-51
Abstract

Ischemia is defined as a reduction in blood flow to a level that is sufficient to alter normal cellular function. Brain tissue is highly sensitive to ischemia, such that even brief ischemic periods in neurons can initiate a complex sequence of events that may ultimately culminate in cell death. Stroke and cardiac arrest induce the cessation of cerebral blood flow, which can result in brain damage. The primary intervention to salvage the brain under such a pathological condition is to restore the cerebral blood flow to the ischemic region. However, paradoxically, restoration of blood flow can cause additional damage and exacerbate the neurocognitive deficits in patients who suffered a brain ischemic event, which is a phenomenon referred... (More)

Ischemia is defined as a reduction in blood flow to a level that is sufficient to alter normal cellular function. Brain tissue is highly sensitive to ischemia, such that even brief ischemic periods in neurons can initiate a complex sequence of events that may ultimately culminate in cell death. Stroke and cardiac arrest induce the cessation of cerebral blood flow, which can result in brain damage. The primary intervention to salvage the brain under such a pathological condition is to restore the cerebral blood flow to the ischemic region. However, paradoxically, restoration of blood flow can cause additional damage and exacerbate the neurocognitive deficits in patients who suffered a brain ischemic event, which is a phenomenon referred to as "reperfusion injury." Transient brain ischemia following a stroke, cardiac arrest, hypoxia, head trauma, cerebral tumor, cerebrovascular disorder, and intracranial infection results from the complex interplay of multiple pathways including excitotoxicity, acidotoxicity, ionic imbalance, peri-infarct depolarization, oxidative and nitrative stress, inflammation, and apoptosis. Many lines of evidence have shown that mitochondria suffer severe damage in response to ischemic injury. Mitochondrial dysfunction based on the mitochondrial permeability transition (MPT) after reperfusion, particularly involving the calcineurin/immunophilin signal transduction pathway, appears to play a pivotal role in the induction of neuronal cell death. Here, we discuss the underlying pathophysiology of brain damage, which is a devastating pathological condition, and highlight the central signal transduction pathway involved in brain damage, which reveals potential targets for therapeutic intervention.

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Please use this url to cite or link to this publication:
author
organization
publishing date
type
Chapter in Book/Report/Conference proceeding
publication status
published
subject
keywords
Calcineurin/immunophilin, Excitotoxicity, Ischemic brain damage, Mitochondrial dysfunction, Mitochondrial permeability transition (MPT), Reperfusion injury
in
Neuroanesthesia and Cerebrospinal Protection
pages
13 pages
publisher
Springer Japan
external identifiers
  • scopus:84956532997
ISBN
9784431544906
9784431544890
DOI
10.1007/978-4-431-54490-6_4
language
English
LU publication?
yes
id
c9586fd1-a987-4c5e-ae17-fd3260454731
date added to LUP
2016-07-05 14:00:20
date last changed
2017-06-08 12:58:55
@inbook{c9586fd1-a987-4c5e-ae17-fd3260454731,
  abstract     = {<p>Ischemia is defined as a reduction in blood flow to a level that is sufficient to alter normal cellular function. Brain tissue is highly sensitive to ischemia, such that even brief ischemic periods in neurons can initiate a complex sequence of events that may ultimately culminate in cell death. Stroke and cardiac arrest induce the cessation of cerebral blood flow, which can result in brain damage. The primary intervention to salvage the brain under such a pathological condition is to restore the cerebral blood flow to the ischemic region. However, paradoxically, restoration of blood flow can cause additional damage and exacerbate the neurocognitive deficits in patients who suffered a brain ischemic event, which is a phenomenon referred to as "reperfusion injury." Transient brain ischemia following a stroke, cardiac arrest, hypoxia, head trauma, cerebral tumor, cerebrovascular disorder, and intracranial infection results from the complex interplay of multiple pathways including excitotoxicity, acidotoxicity, ionic imbalance, peri-infarct depolarization, oxidative and nitrative stress, inflammation, and apoptosis. Many lines of evidence have shown that mitochondria suffer severe damage in response to ischemic injury. Mitochondrial dysfunction based on the mitochondrial permeability transition (MPT) after reperfusion, particularly involving the calcineurin/immunophilin signal transduction pathway, appears to play a pivotal role in the induction of neuronal cell death. Here, we discuss the underlying pathophysiology of brain damage, which is a devastating pathological condition, and highlight the central signal transduction pathway involved in brain damage, which reveals potential targets for therapeutic intervention.</p>},
  author       = {Uchino, Hiroyuki and Chijiiwa, Miyuki and Ogihara, Yukihiko and Elmer, Eskil},
  isbn         = {9784431544906},
  keyword      = {Calcineurin/immunophilin,Excitotoxicity,Ischemic brain damage,Mitochondrial dysfunction,Mitochondrial permeability transition (MPT),Reperfusion injury},
  language     = {eng},
  month        = {08},
  pages        = {39--51},
  publisher    = {Springer Japan},
  series       = {Neuroanesthesia and Cerebrospinal Protection},
  title        = {Molecular mechanisms of brain ischemia and its protection},
  url          = {http://dx.doi.org/10.1007/978-4-431-54490-6_4},
  year         = {2015},
}