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The effect of oxygenation level on cerebral post‐traumatic apoptotsis is modulated by the 18‐kDa translocator protein (also known as peripheral‐type benzodiazepine receptor) in a rat model of cortical contusion
Author(s) -
Soustiel J. F.,
Palzur E.,
Vlodavsky E.,
Veenman L.,
Gavish M.
Publication year - 2008
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/j.1365-2990.2007.00906.x
Subject(s) - translocator protein , tunel assay , hyperoxia , mitochondrion , pathology , biology , endocrinology , chemistry , medicine , immunohistochemistry , microbiology and biotechnology , lung , inflammation , neuroinflammation
Aims: Hyperbaric hyperoxia has been shown to reduce apoptosis in brain injury. As the 18‐kDa translocator protein (TSPO), also known as peripheral‐type benzodiazepine receptor, is closely associated with the mitochondrial transition pore and because of its role in mitochondrial respiration and apoptosis, we hypothesized that reduction of apoptosis by hyperoxia may involve the TSPO. Methods: TSPO and transferase‐mediated dUTP nick end labelling (TUNEL) immunopositivity was first assessed in cortical contusion, created by dynamic cortical deformation, by immunohistochemistry in rats exposed to normoxia [(dynamic cortical deformation (DCD)], normobaric hyperoxia or hyperbaric hyperoxia [hyperbaric oxygen therapy (HBO)]. In a second step, transmembrane mitochondrial potential (Δψ M ) and caspase 9 activity were assessed in the injured area in comparison with the noninjured hemisphere. Measurements were performed in DCD and HBO groups. A third group receiving both HBO and the TSPO ligand PK11195 was investigated as well. Results: TSPO correlated quantitatively and regionally with TUNEL immunopositivity in the perilesional area. Hyperoxia reduced both the number of TSPO expressing and TUNEL positive cells in the perilesional area, and this effect proved to be pressure dependent. After contusion, we demonstrated a dissipation of Δψ M in isolated mitochondria and an elevation of caspase 9 activity in tissue homogenates from the contused area, both of which could be substantially reversed by hyperbaric hyperoxia. This protective effect of hyperoxia was reversed by PK11195. Conclusions: The present findings suggest that the protective effect of hyperoxia may be due to a negative regulation of the proapoptotic function of mitochondrial TSPO, including conservation of the mitochondrial membrane potential.