[Long-term effects of memantine therapy on neonatal rats with hypoxic-ischemic brain damage].
OBJECTIVE
Animal trials have demonstrated that memantine has neuroprotective effects on hypoxic-ischemic (HI) brain damage. Whether memantine can improve the long-term prognosis of rats with HI brain damage has not been reported. This study was designed to investigate the long-term effect of memantine therapy on neonatal rats with HI brain damage.


METHODS
Sixty postnatal 7-day-old newborn rats were randomly assigned into Normal control, HI and Memantine treated groups. Memantine (20 mg/kg) was administered immediately after HI in the Memantine-treated group. All subjects received a 5-day training of Morris water maze test from 23 days old. The escape latency (EL) was recorded at 28 and 35 days old.


RESULTS
The EL values of the Normal control, HI and Memantine-treated groups at 28 days old were 23.1 +/- 21.8, 35.1 +/- 5.3, and 20.6 +/- 3.4 seconds, respectively. There was a significant difference in the EL value between the HI and the Normal control groups (P < 0.05). The EL value of the Normal control, HI and Memantine-treated groups at 35 days old were 19.7 +/- 16.7, 35.6 +/- 32.3, and 16.3 +/- 13.2 seconds, respectively. A prolonged EL induced by HI still existed (P < 0.05 vs Normal controls) but memantine treatment shortened the EL (P < 0.01 vs HI group) at 35 days old.


CONCLUSIONS
Administering memantine immediately after HI can markedly increase the abilities of spatial discrimination, learning and memory and improve the long-term prognosis in rats with HI brain damage.
Gao
Ying
Y
Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
Chen
Hui-Jin
HJ
Qian
Long-Hua
LH
Chen
Guan-Yi
GY
D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008559:Memantine / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018691:Excitatory Amino Acid Antagonists; D018840:HSP70 Heat-Shock Proteins; D008559:Memantine