The Medical Management of Cerebral Edema: Past, Present, and Future Therapies
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CURRENT PERSPECTIVES
The Medical Management of Cerebral Edema: Past, Present, and Future Therapies Michael R. Halstead 1 & Romergryko G. Geocadin 1
# The American Society for Experimental NeuroTherapeutics, Inc. 2019
Abstract Cerebral edema is commonly associated with cerebral pathology, and the clinical manifestation is largely related to the underlying lesioned tissue. Brain edema usually amplifies the dysfunction of the lesioned tissue and the burden of cerebral edema correlates with increased morbidity and mortality across diseases. Our modern-day approach to the medical management of cerebral edema has largely revolved around, an increasingly artificial distinction between cytotoxic and vasogenic cerebral edema. These nontargeted interventions such as hyperosmolar agents and sedation have been the mainstay in clinical practice and offer noneloquent solutions to a dire problem. Our current understanding of the underlying molecular mechanisms driving cerebral edema is becoming much more advanced, with differences being identified across diseases and populations. As our understanding of the underlying molecular mechanisms in neuronal injury continues to expand, so too is the list of targeted therapies in the pipeline. Here we present a brief review of the molecular mechanisms driving cerebral edema and a current overview of our understanding of the molecular targets being investigated. Key Words Cerebral edema . cytotoxic edema . vasogenic edema . hyperosmolar therapy . elevated ICP.
Introduction Cerebral edema is the pathologic accumulation of intracellular and interstitial brain tissue water [1, 2] that is commonly associated with neurologic pathology. The clinical manifestation is largely related to the primary brain pathology and the associated brain edema usually amplifies the dysfunction of the lesioned tissue. The clinical presentation of cerebral edema varies widely depending on the primary brain pathology from asymptomatic, mild worsening of deficits, coma, and brain death. As a potential complication of both primary neurologic and nonneurologic disorders [1], increased burden of cerebral edema correlates with increased morbidity and mortality across diseases [3–6]. A growing understanding of the cellular mechanisms underlying cerebral edema have re-invigorated the scientific community to identify better targeted
* Michael R. Halstead [email protected] 1
Neurosciences Critical Care Division, Departments of Neurology, Anesthesiology-Critical Care Medicine and Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
therapeutics for the management of cerebral edema [2, 7–9]. The focus of this review will be to discuss the distinct cellular pathways leading to cerebral edema, discuss the current and investigational pharmacologic treatment strategies for management of cerebral edema, and briefly discuss the future therapeutic strategies currently being investigated.
Pathophysiology of Cerebral Edema The cellular mechanisms resulting in cerebral edema are divided into
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