The regulatory effect of memantine on expression and synthesis of heat shock protein 70 gene in neonatal rat models with cerebral hypoxic ischemia / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the neuroprotective effect of memantine, a non-competitive antagonist at the N-methyl-D-aspartate receptor, against hypoxic ischemia (HI) by exploring its regulation on the expression and synthesis of heat shock protein 70 (HSP70) gene in neonatal rat models with cerebral HI.</p><p><b>METHODS</b>Memantine was intraperitoneally injected at a dose of 20 mg/kg in neonatal rat models either before (PRE group) or after (POST group) induction of HI. The expression and synthesis of the HSP70 gene and its corresponding product were determined by rapid competitive PCR and immunohistochemistry, respectively.</p><p><b>RESULTS</b>There was an increase in the expression of HSP70 mRNA two hours after induction of HI, which reached its peak at 48 hours, then decreased gradually. The same expression occurred at relatively low levels in the control group. Also, HSP70 synthesis was detected as early as 2h after HI, reached its peak between 48 and 72 hours, then declined over time. After memantine administration, the expression of the gene and its synthesis of the corresponding product decreased significantly during the time intervals 24 - 72 h for the gene and 48 - 72 h for the product compared to the HI group.</p><p><b>CONCLUSION</b>It was shown that HI is very sensitive to the expression of the HSP70 gene and synthesis of its corresponding product, which could be regulated by memantine. The latter may have the ability to reduce brain damage; thus decreased HSP70 mRNA expression could be a marker for HI. It is suggested that memantine can be a promising agent for neuroprotection against HI, although an overall and objective assessment of memantine is required to see if it can be used on neonates clinically later on.</p>

Pathological Research of Cerebral Protection of Memantine in Neonatal Rat Models with Hypoxic-ischemia / 中华围产医学杂志

Objective To investigate the cerebral protection of Memantine in neonatal rats with hypoxic ischemia. Methods Memantine was intraperitoneally injected at a dose of 20 mg/kg in neonatal rats of cerebral hypoxic ischemia (HI). Employing a quantized score system of cerebral pathology for hypoxic ischemia developed, the neuroprotective effect of Memantine was evaluated pathologically. Results There were significantly decreased scores in either PRE group (Memantine was given one hour before HI) or POST group (Memantine was given after HI immediately) comparing to HI group with higher score. Conclusion Memantine can improve cerebral hypoxic ischemic damage significantly, and be potentially valuable for the treatment of neonatal hypoxic ischemic brain damage.