Pathophysiology and treatment of cerebral edema in traumatic brain injury
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AbstractCerebral edema (CE) and resultant intracranial hypertension are associated with unfavorable prognosis in traumatic brain injury (TBI). CE is a leading cause of in-hospital mortality, occurring in >60% of patients with mass lesions, and ∼15% of those with normal initial computed tomography scans. After treatment of mass lesions in severe TBI, an important focus of acute neurocritical care is evaluating and managing the secondary injury process of CE and resultant intracranial hypertension. This review focuses on a contemporary understanding of various pathophysiologic pathways contributing to CE, with a subsequent description of potential targeted therapies. There is a discussion of identified cellular/cytotoxic contributors to CE, as well as mechanisms that influence blood-brain-barrier (BBB) disruption/vasogenic edema, with the caveat that this distinction may be somewhat artificial since molecular processes contributing to these pathways are interrelated. While an exhaustive discussion of all pathways with putative contributions to CE is beyond the scope of this review, the roles of some key contributors are highlighted, and references are provided for further details. Potential future molecular targets for treating CE are presented based on pathophysiologic mechanisms. We thus aim to provide a translational synopsis of present and future strategies targeting CE after TBI in the context of a paradigm shift towards precision medicine. This article is part of the Special Issue entitled "Novel Treatments for Traumatic Brain Injury". Copyright 2018 The Authors
SponsorsRMJ is supported by grants from the National Institute of Neurological Disorders and Stroke ( K23NS101036 ) and a UPP foundation award. PMK is supported by grants from the NINDS ( R01NS087978 ), the U.S. Department of Defense grant WH81XWH-14-2-0018 , and the Eunice Kennedy Shriver National Institute of Child Health and Human Development ( T32HD040686 ). JMS is supported by grants from the Department of Veterans Affairs ( I01BX002889 ), the Department of Defense ( SCI170199 ), the National Heart, Lung, and Blood Institute ( R01HL082517 ) and the NINDS ( R01NS060801 ; R01NS102589 ; R01NS105633 ).
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85051130625&doi=10.1016%2fj.neuropharm.2018.08.004&partnerID=40&md5=690d971fa564f8e4bb958a8455c0236e; http://hdl.handle.net/10713/8549
- A Precision Medicine Approach to Cerebral Edema and Intracranial Hypertension after Severe Traumatic Brain Injury: Quo Vadis?
- Authors: Jha RM, Kochanek PM
- Issue date: 2018 Nov 7
- Cerebral Edema in Traumatic Brain Injury: Pathophysiology and Prospective Therapeutic Targets.
- Authors: Winkler EA, Minter D, Yue JK, Manley GT
- Issue date: 2016 Oct
- Reduction of Cerebral Edema via an Osmotic Transport Device Improves Functional Outcome after Traumatic Brain Injury in Mice.
- Authors: McBride DW, Donovan V, Hsu MS, Obenaus A, Rodgers VG, Binder DK
- Issue date: 2016
- ABCC8 Single Nucleotide Polymorphisms are Associated with Cerebral Edema in Severe TBI.
- Authors: Jha RM, Puccio AM, Okonkwo DO, Zusman BE, Park SY, Wallisch J, Empey PE, Shutter LA, Clark RS, Kochanek PM, Conley YP
- Issue date: 2017 Apr
- [Traumatic brain injury].
- Authors: Hackenberg K, Unterberg A
- Issue date: 2016 Feb
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