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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.

To investigate the neuroprotective effect of L-serine and its underlying mechanisms, focal cerebral ischemia was induced in rats by occlusion of middle cerebral artery (MCAO) with a suture, and reperfusion was given by filament withdrawal 2 hr later. Meanwhile, rat hippocampal neurons were primarily cultured, and incubated in serum-free medium in an incubator containing 1% O(2) for hypoxic exposure of 5 hr, or incubated in serum-free medium containing 1 mM glutamate for glutamate exposure of 2 hr. Brain tissue injury and cell damage were then measured. L-serine dose-dependently decreased the neurology deficit score and infarct volume, elevated the cell viability and inhibited the leakage of lactate dehydrogenase. These effects were blocked by strychnine in both MCAO rats and cultured hippocampal neurons. Furthermore, L-serine (168 mg.kg(-1)) reduced the brain water content, permeability of blood-brain barrier, neuronal loss and the expression of activated caspase-3 in the cortex. In addition, L-serine effectively protected the brain from damage when it was administered within 6 hr after the end of MCAO. It is suggested that L-serine could exert a neuroprotective effect on the ischemic-reperfused brain and on the hypoxia- or glutamate-exposed hippocampal neurons, which may be mediated by activating glycine receptors.

. Although functional glycine receptors (GlyRs) are present in the mature nucleus accumbens (NAcc), an important area of the mesolimbic dopamine system involved in drug addiction, their role has been unclear because the NAcc contains little glycine. However, taurine, an agonist of GlyRs, is abundant throughout the brain, especially during early development. In the present study on freshly dissociated NAcc neurons from young Sprague-Dawley rats (12-to 21-day old), we found that both glycine and taurine can strongly depolarize NAcc neurons and modulate their excitability. In voltage-clamped NAcc neurons, glycine and taurine elicited chloride currents (I Gly and I Tau ) with an EC 50 of 0.12 and 1.25 mM, respectively. The reversal potential of I Gly or I Tau was 0 mV in conventional whole cell mode and -30 mV in gramicidin-perforated mode. At concentrations Ͻ1 mM, both glycine and taurine were very effectively antagonized by strychnine and by picrotoxin (with an IC 50 of 60 nM and 36.5 M for I Gly , and 40 nM and 42.2 M for I Tau ) but were insensitive to 10 M bicuculline. The currents elicited by taurine (Յ1 mM) showed complete cross-desensitization with I Gly , but none with ␥-aminobutyric acid (GABA)-induced currents (I GABA ). However, I Tau elicited by very concentrated taurine (10 mM) showed partial cross-desensitization with I GABA , and it was substantially antagonized by 10 M bicuculline. These results indicate that taurine binds mainly to GlyRs in NAcc, but it could be a partial agonist of GABA A receptors. By activating GlyRs, taurine may play an important physiological role in the control of NAcc function, especially during development.

The present study was designed to investigate the neuroprotective effect of ginseng total saponins (GTSs) and its underlying mechanisms in a rat model of traumatic brain injury (TBI). Rats were injected with GTSs (20 mg/kg, i.p.) or vehicle for 14 days after TBI. Neurological functions were determined using beam balance and prehensile traction tests at 1–14 days after trauma. Brain samples were extracted at 1 day after trauma for determination of water content, Nissl staining, enzyme‐linked immunosorbent assay, immunohistochemistry, terminal deoxynucleotidyl transferase‐mediated biotin‐dUTP nick end labeling, and measurement of oxidative stress variables and inflammatory cytokines. Moreover, the dose response of the neuroprotective effect and time window of the efficacy of GTSs were also determined. We found that treatment of GTSs 1) improved the neurological function with an effective dosage of 5–80 mg/kg and an efficacy time window of 3–6 hr after TBI; 2) reduced brain water content and neuronal loss in the hippocampal CA3 area; 3) increased the activity of superoxide dismutase and decreased the activity of nitric oxide synthase and the amount of malondialdehyde and nitric oxide; 4) down‐regulated interleukin‐1β, interleukin‐6, and tumor necrosis factor‐α and upregulated interleukin‐10 in the cortical area surrounding the injured core; and 5) inhibited the apoptotic cell death and expression of caspase‐3 and bax and raised the expression of bcl‐2. These findings suggest that administration of GTSs after TBI could reduce the secondary injury through inhibiting oxidative and nitrative stress, attenuating inflammatory response, and reducing apoptotic cell death. © 2012 Wiley Periodicals, Inc.

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