Effect of hyperbaric oxygen on neurological recovery of neonatal rats following hypoxic-ischemic brain damage and its underlying mechanism.

OBJECTIVE: To investigate the mechanism underlying the effect of hyperbaric oxygen (HBO) on hypoxic/ischemic brain damage (HIBD) in a neonatal rat model. METHODS: A total of 30 neonatal SD rats aged 7 days were randomly assigned into control group, HIBD group and HBO group (n=10 per group). Following HIBD modeling in neonatal rats, HBO treatment was performed for consecutive 7 days. Immunohistochemistry was done to measure the expression of bone morphogenetic protein-4 (BMP-4) and nestin in the hippocampus. In situ hybridization was employed to detect the mRNA expression of BMP-4 and nestin in the hippocampus. TUNEL staining was done to detect the apoptosis of nerve cells. RESULTS: HIBD was successfully established in the present study. Among three groups, the protein expression of BMP-4 in the hippocampus was the highest in the HBO group, and the smallest in the HIBD group. The BMP-4 expression in the HIBD group was significantly lower than that in the control group. The protein expression of nestin in the hippocampus was the highest in the HBO group, and the smallest in the HIBD group. The nestin protein expression in the hippocampus of HIBD group was significantly lower than that in the control group. The mRNA expression of BMP-4 in the hippocampus was the highest in the HBO group, and the smallest in the HIBD group. The mRNA expression of nestin in the hippocampus was the highest in the HBO group, and the smallest in the HIBD group. The number of apoptotic cells was the largest in the HIBD group, and the number of apoptotic cells in the HBO group was still larger than that in the control group (P<0.01). CONCLUSION: HBO may promote the neurological recovery in neonatal rats with HIBD, which may be attributed to the increased protein and mRNA expression of BMP-4 and nestin in the hippocampus and the inhibition of neural apoptosis.

Early cognitive function of rats with ischemic hypoxic brain injury during the neonatal period / 中华物理医学与康复杂志

Objective To establish an early cognitive disorder model in rats and investigate the early cognitive functioning after ischemic hypoxic brain injury during the neonatal period. Methods Forty-six newborn Sprague-Dawley rats were randomized into a 21-d-old group and a 31-d-old group. These 2 groups were then subdivided into model and sham-operated subgroups (M21, n=12; SH21, n=11; M31, n=12; SH31, n=11). A model of neonatal early cognitive disorder was established in the rats of the M21 and M31 groups using a modification of Rice's method. Rats in the SH21 and SH31 groups received skin incisions and common carotid artery separation without ligation or hypoxia. Each group was tested with a Morris water maze. The rats were sacrificed after testing, and brain tissue was examined under the electron microscope. Nissl staining allowed Nissl body quantification and neurocyte acin the M21 group was significantly longer than in the SH21 group. The 31-d-old subgroups had shorter average escaping latencies than the corresponding 21-d-old subgroups. (b) Spatial memory: The average platform times, Ⅰ region times and Ⅰ region distances showed no significant differences among groups. ②Brain pathology (a) Gross appearance: Obvious ischemic hemisphere atrophy was observed in the M group, and no abnormality was observed in the SH group. (b) Electron microscopic observation: In the SH group cell ultrastructures in the ischemic hippocampus were normal. Karyopyknosis and dilated endoplasmic reticulums were found in the M group. More mitochondria were found in the presynaptic membranes of the ischemic hippocampus in the M group than that in the SH group. (c) Nissl body quantification and neurocyte activity analysis: Significantly less activity in the ischemic cortex was found in the M21 group compared to the SH21 group. More activity was observed in the 31-d-old subgroups than in the corresponding 21-d-old subgroups. Conclusions ①The neonatal rats with ischemic hypoxic brain injury had prolonged average escaping latency and depressed neuronal activity. ②The 31-d-old rats had better spatial localization learning ability than the 21-d-old rats.