Injecting erythropoietin into lateral ventricle and abdominal subcutaneous tissue improves the learning and memory ability of rats with vascular dementia

摘要

BACKGROUND: It is found in recent studies that erythropoietin (EPO) has protective effect on ischemic /hypoxic injury in central nervous system (CNS). Most of neuroprotective studies of EPO are aimed at nerve cells cultured in vitro, and whether or not EPO can improve cognitive function of rats with vascular dementia (VaD) induced by ischemic and hypoxic injury is still unclear. OBJECTIVE: To observe the effect of injecting EPO into lateral ventricle and abdominal subcutaneous tissue on learning and memory ability of rats with VaD. DESIGN: Randomized and controlled experiment. SETTING: Department of Neurology, Changzheng Hospital, Second Military Medical University of Chinese PLA. MATERIALS: Eight-six Wistar rats, aged > 16 months, weighing (300±41) g, of either gender, were provided by the Experimental Animal Center of the Second Military Medical University of Chinese PLA. Y-maze (type MG-3) was purchased from Zhangjiagang Biomedical Instrument Factory. EPO was produced by Shenyang Sunshine Pharmaceutical Co., Ltd. (No. S19980074). METHODS: This experiment was carried out in the laboratory of Department of Neurology, Changzheng Hospital, Second Military Medical University of Chinese PLA between July 2003 and December 2005. Animal models of VaD were developed by the method of permanent ligation of bilateral common carotid artery. Eighty-six rats were randomly divided into 4 groups: ① Sham-operation group (n =18): Bilateral common carotid artery was isolated. Suture was buried without ligation. ② Model group (n =21): Rat models of vascular dementia were developed. ③Lateral cerebral ventricle injection group (n =26): Following a cannula was buried in lateral cerebral ventricle for one week, rat models of vascular dementia were developed and injected with 200 U/kg recombinant human EPO (rhEPO) via lateral cerebral ventricle, 3 times a week.④ Intraperitoneal injection group (n =21): After rat models of VaD were developed, they were intraperitoneally injected with 1 250 U/kg rhEPO, 3 times a week. Rats in the sham-operation group and model group were intraperitoneally injected with the same amount of normal saline. Error number and total reaction time (TRT) of rats were detected before and 4,8 and 12 weeks after operation by Y-maze test to evaluate spatial learning and memory ability. MAIN OUTCOME MEASURES: Error number and TRT at postoperative 4,8 and 12 weeks in each group. RESULTS: Eighty-six rats were involved, 21 died due to accident or lost due to cannula, finally 65 were involved in final analysis. There were no significant differences in error number and TRT before operation among groups (P > 0.05). At postoperative 4, 8 and 12 weeks, error number of model group was (2.68±0.73), (8.25±1.72), (13.74±2.12) times, respectively, that of lateral cerebral ventricle injection group was (2.14±0.92), (5.39±1.31), (10.78±1.95) times, respectively, and that of intraperitoneal injection group was (2.21±0.98), (5.88±1.56), (10.97±1.98), respectively; At postoperative 4, 8 and 12 weeks, TRT of model group was (163.35±6.72), (222.22±9.29), (285.25±5.04) s, respectively, that of lateral cerebral ventricle injection group was (130.29±5.19), (178.94±4.72), (225.00±3.70) s, respectively , and that of intraperitoneal injection group was (135.04±5.62), (186.67±4.27), (228.89±3.37) s, respectively. The error number and TRT in the three group were significantly superior to that of sham-operation group separately [(0.98±0.67), (0.97±0.72), (0.89±0.69); (100.63±1.93), (101.13±3.05), (107.25±1.98) s, P 0.05). CONCLUSION: Both lateral cerebral ventricle and intraperitoneal injection of EPO can improve learning and memory ability of rats with VaD. Meanwhile, it is indirectly proved that EPO functions its effects after entering into brain via blood brain barrier.