title: Multifaceted roles for astrocytes in spreading depolarization: A target for limiting spreading depolarization in acute brain injury?
abstract: Spreading depolarizations (SDs) are coordinated waves of synchronous depolarization, involving large numbers of neurons and astrocytes as they spread slowly through brain tissue. The recent identification of SDs as likely contributors to pathophysiology in human subjects has led to a significant increase in interest in SD mechanisms, and possible approaches to limit the numbers of SDs or their deleterious consequences in injured brain. Astrocytes regulate many events associated with SD. SD initiation and propagation is dependent on extracellular accumulation of K(+) and glutamate, both of which involve astrocytic clearance. SDs are extremely metabolically demanding events, and signaling through astrocyte networks is likely central to the dramatic increase in regional blood flow that accompanies SD in otherwise healthy tissues. Astrocytes may provide metabolic support to neurons following SD, and may provide a source of adenosine that inhibits neuronal activity following SD. It is 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 vascular responses after SD. Direct or indirect evidence has accumulated implicating astrocytes in many of these responses, but much remains unknown about their specific contributions, especially in the context of injury. Conversion of astrocytes to a reactive phenotype is a prominent feature of injured brain, and recent work suggests that the different functional properties of reactive astrocytes could be targeted to limit SDs in pathophysiological conditions.
authors: Stroke and Neurovascular Regulation Lab, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts.
authors: Jessica L
authors: JL
authors: Seidel
authors: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département des Sciences du Vivant (DSV), Institut d'Imagerie Biomédicale (I2BM), Molecular Imaging Center (MIRCen), CNRS UMR 9199, Université Paris-Sud, Université Paris-Saclay, F-92260 Fontenay-aux-Roses, France.
authors: Carole
authors: C
authors: Escartin
authors: Stroke and Neurovascular Regulation Lab, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts.|Stroke Service and Neuroscience Intensive Care Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts.
authors: Cenk
authors: C
authors: Ayata
authors: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département des Sciences du Vivant (DSV), Institut d'Imagerie Biomédicale (I2BM), Molecular Imaging Center (MIRCen), CNRS UMR 9199, Université Paris-Sud, Université Paris-Saclay, F-92260 Fontenay-aux-Roses, France.
authors: Gilles
authors: G
authors: Bonvento
authors: Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico.
authors: C William
authors: CW
authors: Shuttleworth
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001930:Brain Injuries / Q000503:physiopathology / Q000628:therapy; D013181:Cortical Spreading Depression / Q000502:physiology*; D006801:Humans
keywords: Ca2+; adenosine; glutamate; migraine; neurovascular coupling; reactive astrocyte; spreading depression; stroke; traumatic brain injury; waves