CNS & Neurological Disorders - Drug Targets

(Formerly Current Drug Targets - CNS & Neurological Disorders)

Stephen D. Skaper  
Department of Pharmaceutical and Pharmacological Sciences
University of Padova
Padova
Italy

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Mitochondrial Neuroprotection in Traumatic Brain Injury: Rationale and Therapeutic Strategies

Author(s): Shoji Yokobori, Anna T. Mazzeo, Shyam Gajavelli and Malcolm R. Bullock

Affiliation: Department of Neurosurgery, University of Miami Miller School of Medicine, Lois Pope LIFE Center, Room 3-20, 1095 NW 14th Terrace, Miami, FL 33136, USA.

Keywords: Apoptosis, astrocyte-neuron lactate shuttle, cyclosporine A, mitochondrial dysfunction, mitochondrial permeability transition pore, secondary brain injury, traumatic brain injury.

Abstract:

Traumatic brain injury (TBI) is still the worldwide, leading cause of mortality and morbidity in young adults. The prognosis of TBI patients is strongly affected by secondary brain damage including mitochondrial dysfunctions. In many basic and clinical studies, mitochondrial dysfunctions, including the opening of mitochondrial permeability transition (mPT) pore, and treatments including cyclosporine A (CsA) have been studied. These evidences suggest an important role for mitochondria as therapeutic targets for neuroprotection after TBI.

This review summarizes the data about normal and pathological mitochondrial function after TBI, TBI pathobiology relating to mitochondrial dysfunction and therapeutic strategies including drug treatment. This review also mentioned about glucose, lactate, and pyruvate metabolisms in TBI, including the "astrocyte-neuron lactate shuttle (ANLS)" hypothesis. Mitochondrial pathophysiology in TBI is still unclear.

Thus, the pharmacological treatment in TBI patient is still challenging. This review could help further understanding of this topic. Hopefully, this could help further development and innovation for drug therapies in TBI.

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Article Details

VOLUME: 13
ISSUE: 4
Page: [606 - 619]
Pages: 14
DOI: 10.2174/187152731304140702112805