Multifaceted roles for astrocytes in spreading depolarization: A target for limiting spreading depolarization in acute brain injury?
Résumé
Spreading depolarizations (SDs) are coordinated waves of synchronous depolarization, involving large numbers of neuronsand astrocytes as they spread slowly through brain tissue. The recent identification of SDs as likely contributors to pathophys-iology in human subjects has led to a significant increase in interest in SD mechanisms, and possible approaches to limit thenumbers of SDs or their deleterious consequences in injured brain. Astrocytes regulate many events associated with SD. SDinitiation and propagation is dependent on extracellular accumulation of K$^$ and glutamate, both of which involve astrocyticclearance. SDs are extremely metabolically demanding events, and signaling through astrocyte networks is likely central tothe dramatic increase in regional blood flow that accompanies SD in otherwise healthy tissues. Astrocytes may provide meta-bolic support to neurons following SD, and may provide a source of adenosine that inhibits neuronal activity following SD. Itis also possible that astrocytes contribute to the pathophysiology of SD, as a consequence of excessive glutamate release,facilitation of NMDA receptor activation, brain edema due to astrocyte swelling, or disrupted coupling to appropriate vascu-lar responses after SD. Direct or indirect evidence has accumulated implicating astrocytes in many of these responses, butmuch remains unknown about their specific contributions, especially in the context of injury. Conversion of astrocytes to areactive phenotype is a prominent feature of injured brain, and recent work suggests that the different functional propertiesof reactive astrocytes could be targeted to limit SDs in pathophysiological conditions
Domaines
NeurobiologieOrigine | Fichiers éditeurs autorisés sur une archive ouverte |
---|