Department of Pediatrics, Shenzhen Fourth People’s Hospital, Guangdong Medical College, Shenzhen   518033, Guangdong Province, China

Li He, Chief physician, Department of Pediatrics, Shenzhen Fourth People’s Hospital, Guangdong Medical College, Shenzhen   518033, Guangdong Province, China Supported by Shenzhen Science and Technology Bureau, No.200405204* He L, Deng JY, He WD. Flunarizine and lamotrigine prophylaxis effects on neuron-specific enolase, S-100, and brain-specific creatine kinase in a fetal rat model of hypoxic-ischemic brain damage. Neural Regen Res 2008;3(7):768-71

Abstract

BACKGROUND: Calcium antagonists may act as neuroprotectants, diminishing the influx of calcium ions through voltage-sensitive calcium channels. When administered prophylactically, they display neuroprotective effects against hypoxic-ischemic brain damage in newborn rats.

OBJECTIVE: To investigate the neuroprotective effects of flunarizine (FNZ), lamotrigine (LTG) and the combination of both drugs, on hypoxic-ischemic brain damage in fetal rats.

DESIGN AND SETTING: This randomized, complete block design was performed at the Department of Pediatrics, Shenzhen Fourth People’s Hospital, Guangdong Medical College.

MATERIALS: Forty pregnant Wistar rats, at gestational day 20, were selected for the experiment and were randomly divided into FNZ, LTG, FNZ + LTG, and model groups, with 10 rats in each group.

METHODS: Rats in the FNZ, LTG, and FNZ + LTG groups received intragastric injections of FNZ    (0.5 mg/kg/d), LTG (10 mg/kg/d), and FNZ (0.5 mg/kg/d) + LTG (10 mg/kg/d), respectively. Drugs were administered once a day for 3 days prior to induction of hypoxia-ischemia. Rats in the model group were not administered any drugs. Three hours after the final administration, eight pregnant rats from each group underwent model establishment hypoxia-ischemia brain damage to the fetal rats. Cesareans were performed at 6, 12, 24, and 48 hours later; and 5 fetal rats were removed from each mother and kept warm. Two fetuses without model establishment were removed by planned cesarean at the same time and served as controls. A total of 0.3 mL serum was collected from fetal rats at 6, 12, 24, and 48 hours, respectively, following birth.

MAIN OUTCOME MEASURES: Serum protein concentrations of neuron-specific enolase and S-100 were measured by ELISA. Serum concentrations of brain-specific creatine kinase were measured using an electrogenerated chemiluminescence method.

RESULTS: Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly higher in the hypoxic-ischemic fetal rats, compared with the non-hypoxic-ischemic group. Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly less in the FNZ, LTG, and FNZ + LTG groups following ischemia, compared with the model group (P < 0.01). However, these values were significantly greater in the FNZ and LTG groups, compared with the  FNZ + LTG group, following ischemia (P < 0.01).

CONCLUSION: Preventive antenatal use of oral FNZ and LTG has positive neuroprotective effects on intrauterine hypoxic-ischemic brain damage. The combined effect of these two drugs is superior.

Key Words: flunarizine; lamotrigine; hypoxic-ischemic brain damage; neuron-specific enolase; S-100; brain-specific creatine kinase

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