Attenuating inflammation but stimulating both angiogenesis and neurogenesis using hyperbaric oxygen in rats with traumatic brain injury

Abstract

BACKGROUND: 

Inflammation, angiogenesis, neurogenesis, and gliosis are involved in traumatic brain injury (TBI). Several studies provide evidence supporting the neuroprotective effect of hyperbaric oxygen (HBO₂) therapy in TBI. The aim of this study was to ascertain whether inflammation, angiogenesis, neurogenesis, and gliosis during TBI are affected by HBO₂ therapy.

METHODS: 

Rats were randomly divided into three groups: TBI + NBA (normobaric air: 21% O₂ at 1 absolute atmospheres), TBI + HBO₂, and Sham operation + NBA. TBI + HBO₂ rats received 100% O₂ at 2.0 absolute atmospheres for 1 hr/d for three consecutive days. Behavioral tests and biochemical and histologic evaluations were done 4 days after TBI onset.

RESULTS: 

TBI + NBA rats displayed: (1) motor and cognitive dysfunction; (2) cerebral infarction and apoptosis; (3) activated inflammation (evidenced by increased brain myeloperoxidase activity and higher serum levels of tumor necrosis factor-α); (4) neuronal loss (evidenced by fewer NeuN-positive cells); and (5) gliosis (evidenced by more glial fibrillary protein-positive cells). In TBI + HBO₂ rats, HBO₂ therapy significantly reduced TBI-induced motor and cognitive dysfunction, cerebral infarction and apoptosis, activated inflammation, neuronal loss, and gliosis. In addition, HBO₂ therapy stimulated angiogenesis (evidenced by more bromodeoxyuridine-positive endothelial and vascular endothelial growth factor-positive cells), neurogenesis (evidenced by more bromodeoxyuridine-NeuN double-positive and glial cells-derived neurotrophic factor-positive cells), and overproduction of interleukin-10 (an anti-inflammatory cytokine).

CONCLUSIONS: 

Collectively, these results suggest that HBO₂ therapy may improve outcomes of TBI in rats by inhibiting activated inflammation and gliosis while stimulating both angiogenesis and neurogenesis in the early stage.