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Involvement of Apoptosis-Inducing Factor (AIF) in Neuronal Cell Death Following Cerebral Ischemia

  • Nikolaus Plesnila
  • Carsten Culmsee
Chapter

Abstract

Delayed neuronal death is a hallmark of infarct development and sustained functional impairment in rodent models of focal cerebral ischemia, an experimental paradigm resembling ischemic stroke in humans. The exact molecular pathophysiology of this still enigmatic event is not only of academic interest but may hold the key for novel therapeutic strategies for human stroke. There is general understanding that acute lack of perfusion leads to rapid necrotic-oncotic cell death in the core of the ischemic infarct. In contrast, conditions associated with severely reduced, but not immediately lethal reductions of cerebral blood flow in the ischemic penumbra likely result in delayed and more programmed type of neuronal cell death. Based on results first obtained from non-neuronal cells, cysteine aspartate proteases (caspases) were described as key modulators of this process. More recently, however, it became clear that also caspase-independent mechanisms play a significant role for ischemia-induced delayed neuronal cell loss. In this chapter, we review the role of one of the first described caspase-independent cell death proteins, apoptosis-inducing factor (AIF), for post-ischemic brain damage. Our conclusion is that there is compelling evidence for a causal role of AIF in neuronal cell death following experimental stroke and other neurological disorders associated with cerebral ischemia. Hence, AIF and other, more recently described subtypes of caspase-independent cell death may provide promising targets for therapeutic interventions in cerebrovascular disease.

Keywords

Stroke Focal cerebral ischemia Apoptosis inducing factor AIF Programmed cell death 

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute for Stroke and Dementia Research (ISD)University of Munich Medical CenterMunichGermany
  2. 2.Clinical Pharmacy—Pharmacology and Toxicology, Faculty of PharmacyPhilipps-University of MarburgMarburgGermany

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