Long-term Effects of Hyperbaric Oxygen Therapy on Neonatal Rats with Hypoxic-ischemic Brain Injury

[Objective] To evaluate the long-term effects of early and delayed hyperbaric oxygen (HBO) therapy on neonatal rats with hypoxic-ischemic brain injury (HIBD). [Method] Postnatal 7 days (PD7) pups (n=37) were randomly set into 4 groups: Control (n=10, pseudo operation), HIBD group (n=9, the left common carotid was dissected and ligated. After 1-2h recovery, the pups were exposed to 8% oxygen-92% nitrogen gas mixture for 2h), EHBO group (n=9, group of early HBO therapy, pups began to HBO treatment with 2 atmosphere absolutes, 2×30min at a 24h intervals just 0.5-1 h after the HIBD model), or LHBO group (n=9, group of delayed HBO therapy, pups began to HBO treatment with 2 atmosphere absolutes, 5×30min at a 24 h intervals just 48-72 h after the HIBD model). For evaluating the HBO interference effect, we measured the spatial learning and memory ability in the Morris water maze, and survival neurons in CAl region of hippocampus. [Results] Compared with control, the rats in HIBD group displayed significant morphologically and histological deficits, as well as severe learning and memory disability. In Morris water maze, mean escape latency in HIBD group were longer (56.35s vs. 23.07s, P＜0.05), probe time and probe length were shorter (29.29s vs 51.21s and 548cm vs 989cm respectively, P＜0.05), and survival neurons in CAl region were less (100/mm vs.183/mm, P＜0.05). Early HBO therapy resulted in protection against both HIBD- induced brain tissue loss and spatial learning and memory disability (mean escape latency: 39.17s vs 56.35s, probe time: 36.84s vs 29.29s, probe length: 686cm vs 548cm, survival neurons: 131/mm vs 100/mm, P＜0.05). Delayed HBO therapy did not showed improvement of either spatial learning and memory or brain tissue loss (mean escape latency: 56.25s vs 56.35s, probe time: 30.11s vs 29.29s, probe length: 572 cm vs 548 cm, survival neurons: 95/mm vs 100/mm, P＞0.05). There was a close linear correlation between the CAl survival neurons and the mean escape latency for block 9 acquisition trials (r=-0.819, P＜0.01). [Conclusion] Early HBO therapy decreased the degree of HIBD and improved the long-term deficiency of learning and memory function induced by HIBD, but delayed HBO therapy had no effect on treating HIBD.