[Long-term effects of early hyperbaric oxygen therapy on neonatal rats with hypoxic-ischemic brain damage].
OBJECTIVE
The application and therapeutic effect of hyperbaric oxygen (HBO) in hypoxic-ischemic brain damage (HIBD) remains controversial. Previous studies have focused on the early pathological and biochemical outcomes and there is a lack of long-term functional evaluation. This study was designed to evaluate the long-term pathological and behavioral changes of early HBO therapy on neonatal rats with HIBD.


METHODS
Postnatal 7 days (PD7) rat pups were randomly assigned into Control (n=18), HIBD (n=17) and HBO treatment groups (n=17). HIBD was induced by ligating the left common carotid, followed by 2 hrs hypoxia exposure in the HIBD and HBO treatment groups. The Control group was sham-operated and was not subjected to hypoxia exposure. The HBO therapy with 2 atmosphere absolutes began 0.5-1 hr after HIBD in the HIBD treatment group, once daily for 2 days. The spatial learning and memory ability were evaluated by the Morris water maze test at PD37 to PD41. The morphological and histological changes of the brain, including brain weight, survival neurons, AchE positive unit and NOS positive neurons in hippocampal CA1 region, were detected at PD42.


RESULTS
The rats in the HIBD group displayed significant morphological and histological deficits, as well as severe spatial learning and memory disability. In the Morris water maze test, the mean escape latency were longer (56.35 +/- 22.37 s vs 23.07 +/- 16.28 s; P < 0.05) and the probe time and probe length were shorter in the HIBD group (29.29 +/- 6.06 s vs 51.21 +/- 4.59 s and 548 +/- 92 cm vs 989 +/- 101 cm; both P < 0.05) compared with the Control group. The left brain weight in the HIBD group was lighter than that in the Control group (0.601 +/- 0.59 g vs 0.984 +/- 0.18 g; P < 0.05). The survival neurons in the hippocampal CA1 region were less (100 +/- 27/mm vs 183 +/- 8/mm; P < 0.05), as well as the AchE-positive unit and NOS-positive neurons (18.50 +/- 2.24% vs 27.50 +/- 2.18% and 19.25 +/- 4.33 vs 33.75 +/- 5.57 respectively; P < 0.05) after HIBD. Early HBO treatment improved the abilities of spatial learning and alleviated the morphological and histological damage. The mean escape latency (39.17 +/- 21.20 s) was shortened, the probe time (36.84 +/- 4.36 s) and the probe length (686 +/- 76 cm) were longer, and the brain weight (0.768 +/- 0.85 g), the survival neurons (133 +/- 25/mm) and the AchE-positive unit (21.94 +/- 2.73%) increased significantly compared with those of the HIBD group (P < 0.05).


CONCLUSIONS
Early HBO treatment resulted in a protective effect against HIBD-induced long-term brain morphological and histological deficits and spatial learning and memory disability.
Liu
Mei-Na
MN
Department of Pediatrics, First Affiliated Hospital of Sun Yet-sen University, Guangzhou 510080, China.
Zhuang
Si-Qi
SQ
Zhang
Hong-Yu
HY
Qin
Zhao-Yuan
ZY
Li
Xiao-Yu
XY
D000110:Acetylcholinesterase / Q000032:analysis; D000818:Animals; D001921:Brain / Q000473:pathology; D004924:Escape Reaction; D005260:Female; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology; D006931:Hyperbaric Oxygenation; D020925:Hypoxia-Ischemia, Brain / Q000201:enzymology / Q000473:pathology / Q000628:therapy*; D008297:Male; D018782:Maze Learning; D019001:Nitric Oxide Synthase / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D019001:Nitric Oxide Synthase; D000110:Acetylcholinesterase