Oligodendrocyte pathophysiology and treatment strategies in cerebral ischemia.
Oligodendrocytes (OLs), the myelin-forming cells of the central nervous system, form a functional unit with axons and play a crucial role in axonal integrity. An episode of hypoxia-ischemia causes rapid and severe damage to these particularly vulnerable cells via multiple pathways such as overactivation of glutamate and ATP receptors, oxidative stress, and disruption of mitochondrial function. The cardinal effect of OL pathology is demyelination and dysmyelination, and this has profound effects on axonal function, transport, structure, metabolism, and survival. The OL is a primary target of ischemia in adult-onset stroke and especially in periventricular leukomalacia and should be considered as a primary therapeutic target in these conditions. More emphasis is needed on therapeutic strategies that target OLs, myelin, and their receptors, as these have the potential to significantly attenuate white matter injury and to establish functional recovery of white matter after stroke. In this review, we will summarize recent progress on the role of OLs in white matter ischemic injury and the current and emerging principles that form the basis for protective strategies against OL death.
Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, Malta.
Gabriella
G
Mifsud
Christian
C
Zammit
Richard
R
Muscat
Giuseppe
G
Di Giovanni
Mario
M
Valentino
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D009836:Oligodendroglia / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D000255:Adenosine Triphosphate
Excitotoxicity; Hypoxia-ischemia; Oligodendrocyte; Oxidative stress; White matter