[Therapeutic efficacy of hyperbaric oxygen on traumatic brain injury in the rat and the underlying mechanisms].

OBJECTIVE: To investigate the effects of hyperbaric oxygen (HBO) treatment on the activation of astrocytes and the expression of glia-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) in the brain after traumatic brain injury (TBI). METHODS: 54 male SD rats were randomly divided into three groups (n = 18): sham-operated, TBI and HBO treatment groups. TBI was induced with Feeney's method, bone window was opened without strike on the brain tissue in the sham-operated group. HBO group rats received HBO treatment for 60 min in the hyperbaric chamber containing O2 100% at 3 ATA. When neurological functions were measured 48 h after TBI, rats were decapitated, the brain water content of 18 rats was measured, 18 brains were sliced for the morphological observation after Nissl staining and for the immunohistochemistry staining of astrocyte markers glial fibrillary acidic protein (GFAP), vimentin and S100, and the other 18 brains of injured side were used for Western blot analysis of GDNF and NGF. RESULTS: HBO treatment reduced the neurological deficit, brain water content and hippocampal neuronal loss. In the observed cortex and hippocampal area astrocytes were activated, the cell number of positive expression of astrocyte markers GFAP, vimentin and S100 was increased, and the expression of GDNF and NGF was elevated after TBI. However, these indices were all enhanced further after the HBO treatment. CONCLUSION: It is suggested that HBO may be an effective therapy for TBI and upregulation of the expression of GDNF and NGF may underly the effect of HBO.

Neuroprotective effects of hyperbaric oxygen treatment on traumatic brain injury in the rat.

This study was designed to evaluate the potential benefits of hyperbaric oxygen (HBO) in the treatment of traumatic brain injury (TBI). The right cerebral cortex of rats was injured by the impact of a 20-g object dropped from a predetermined height. The rats received HBO treatment at 3 ATA for 60 min after TBI. Neurological behavior score, brain water content, neuronal loss in the hippocampus, and cell apoptosis in brain tissue surrounding the primary injury site were examined to determine brain damage severity. Three and six hours after TBI, HBO-treated rats displayed a significant reduction in brain damage. However, by 12 h after TBI, the efficacy of HBO treatment was considerably attenuated. Furthermore, at 24, 48, and 72 h after TBI, the HBO treatment did not show any notable effects. In contrast, multiple HBO treatments (three or five times in all), even when started 48 h after TBI, remarkably reduced neurology deficit scores and the loss of neuronal numbers in the hippocampus. Although multiple treatments started at 48 h significantly improved neurological behaviors and reduced brain injury, the overall beneficial effects were substantially weaker than those seen after a single treatment at 6 h. These results suggest that: (1) HBO treatment could alleviate brain damage after TBI; (2) a single treatment with HBO has a time limitation of 12 h post-TBI; and (3) multiple HBO treatments have the possibility to extend the post-TBI delivery time window. Therefore, our results clearly suggest the validity of HBO therapy for the treatment of TBI.

[Experimental study of therapeutic time window of L-serine against focal cerebral ischemia/reperfusion injury in rats].

OBJECTIVE: To observe the therapeutic time window of L-serine against focal cerebral ischemia/reperfusion injury in rats, and related mechanisms. METHODS: Sprague-Dawley rats were randomly divided into six groups (n=6), sham-operation group, vehicle group, 3, 6, 12 and 24 h treatment group of L-serine. Focal cerebral ischemia was induced with the method of middle cerebral artery occlusion (MCAO) in rats, and reperfusion was emerged by removing the thread 2 h later. The treatment of L-serine (200 mg/kg ip) was begun at 3, 6, 12 and 24 h after MCAO respectively, and subsequently repeated once 12 h. The vehicle group was intraperitoneally injected with isodose normal saline. The neurological behavior score and cerebral infarction volume was measured 48 h after reperfusion. In addition, the contents of malondialdehyde (MDA), activity of superoxide dismetase (SOD), the levels of inflammatory cytokines (TNF-alpha, IL-6) and ultrastructure of neuron in brain tissue were investigated. RESULTS: Compared with the vehicle group, treatments with L-serine both 3 and 6 h after MCAO decreased the neurology deficit score and infarct volume. Only neurology deficit score had been reduced 12 h after MCAO, while no neuropmrotective effects had been observed during 24 h. Furthermore, L-serine elevated the content of SOD, decreased the level of MDA, TNF-alpha and IL-6 in ischemic brain tissue, and alleviated the injury of the neuronal ultrastructure. CONCLUSION: L-serine exerted a time-dependent neuroprotective effect on the brain after MCAO in rat. This effect might be possibly mediated through following mechanisms: lessening oxidative stress and reducing the release of inflammatory cytokines.