Involvement of the Mitochondrial Benzodiazepine Receptor in Traumatic Brain Injury: Therapeutic Implications

Author(s): Eugene Vlodavsky, Eilam Palzur, Jean F. Soustiel.

Journal Name: CNS & Neurological Disorders - Drug Targets

Volume 13 , Issue 4 , 2014

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Abstract:

Traumatic brain injuries represent the leading cause of death and morbidity in young adults in western countries, and are responsible for a major social and economical burden. For decades, the mainstay of neurotrauma management has been represented by control of post-traumatic edema. With the emergence of a better understanding of the underlying cellular mechanisms responsible for the generation of secondary brain damage, the hope for the "magic bullet" has prompted the development of novel drugs that have repeatedly failed to significantly improve outcome of head-injured patients. During the past decade, mitochondrial functional and structural impairment has emerged as a pivotal event in the pathway of cell to secondary death. Extensive research has identified a vast range of deleterious signals that are generated and integrated at the mitochondrial level resulting in impairment of major mitochondrial functions such as calcium homeostasis, free radicals generation and detoxification, energy production and neurosteroidogenesis. Mitochondria have therefore emerged as a potential therapeutic target. Within the spectrum of major mitochondrial structural components, the 18 kDa translocator protein (TSPO) has shown important and relevant functions such as steroid synthesis and modulation of the mitochondrial permeability transition that may substantially affect the fate of injured cells. This review summarizes the potential therapeutic implications of TSPO modulation in traumatic brain injury in the view of the current knowledge on this intriguing mitochondrial complex.

Keywords: Mitochondria, 18 kDa translocator protein, mitochondrial permeability transition pore, traumatic brain injury.

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Article Details

VOLUME: 13
ISSUE: 4
Year: 2014
Page: [620 - 629]
Pages: 10
DOI: 10.2174/187152731304140702114630
Price: $58

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