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Neuroanesthesia and Cerebrospinal Protection pp 39–51Cite as

Molecular Mechanisms of Brain Ischemia and Its Protection

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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 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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Authors and Affiliations

  1. Department of Anesthesiology, Tokyo Medical University, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan

    Hiroyuki Uchino, Miyuki Chijiiwa & Yukihiko Ogihara

  2. Mitochondrial Pathophysiology Unit, Department of Clinical Sciences, Lund University, Box 117, 221 00, Lund, Sweden

    Eskil Elmer

Authors
  1. Hiroyuki Uchino
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  2. Miyuki Chijiiwa
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  3. Yukihiko Ogihara
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  4. Eskil Elmer
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Correspondence to Hiroyuki Uchino .

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Editors and Affiliations

  1. Tokyo Medical University, Tokyo, Japan

    Hiroyuki Uchino

  2. Kurume University, Fukuoka, Fukuoka, Japan

    Kazuo Ushijima

  3. Tokyo Medical University Hachioji Medical Center, Tokyo, Tokyo, Japan

    Yukio Ikeda

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Uchino, H., Chijiiwa, M., Ogihara, Y., Elmer, E. (2015). Molecular Mechanisms of Brain Ischemia and Its Protection. In: Uchino, H., Ushijima, K., Ikeda, Y. (eds) Neuroanesthesia and Cerebrospinal Protection. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54490-6_4

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  • DOI: https://doi.org/10.1007/978-4-431-54490-6_4

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-54489-0

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