Effect of tacrolimus on neural behaviors and memory of rats with traumatic brain injury
- VernacularTitle:他克莫司对创伤性脑损伤大鼠神经行为和记忆能力的影响
- Author:
Xu SUN
;
Guiyun ZHANG
;
Qiuping LI
;
Yaoyuan CUI
;
Minghai WEI
- Publication Type:Journal Article
- From:
Chinese Journal of Tissue Engineering Research
2005;9(24):250-252
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND:At present, many researches have shown that tacrolimus has protecting effect on peripheral nerves,however,whether tacrolimus has a similar effect on central neural system has not been known yet.OBJECTIVE:To investigate the effect of tacrolimus on neural behaviors and memory by observing the neural behaviors and detecting the expression of synaptophysin in cortex,hippocampus and basipodite.DESIGN:Parallel and before and post contrast study.SETTING:Department of neurosurgery, affiliated hospital of the two medical universities.MATERIALS:The experiment was carried out in the Laboratory of Department Neurosurgery,Shanghai Changzheng Hospital in November 2002.Twenty-four qualified Sprague-Dawley rats supplied by Shanghai Experimental Animal Center of medical institution of Fudan University,with body mass of 180-220 g,were randomly divided into three groups:control, injury and treatment,with 8 rats in each group.INTERVENTIONS:Anesthesia was induced by administration of sodium pentobarbital(with the concentration of 20 g/L,40 mg/kg) twenty-four hours before the operation.The coup energy was 151.95-172.21 kPa that was equal to medium injury. The control rats did not receive the coup. Tacrolimus was given to the treatment group in the dosage of 1 mg/kg body weight by intraperitoneal injection at 5 minutes post trauma. The drug was given once physiological saline. Before and post trauma (on the third and seventh day)all rats Accepted Beam Walking Test,Beam Balance Test and Memory Test,respectively. One week after trauma,all rats' heads was removed and the brain was taken out within seconds.The hippocampus,cortex and basipodite of the traumatic hemisphere were kept in methanal with the concentration of 4 percent. Immunohistochemistry and image analysis system were used to study the expression of synaptophysin in cortex,hippocampus and basipodite of the traumatic hemisphere.MAIN OUTCOME MEASURES: ①The performance records of neural behaviors and memory of the three groups. ②Results of the expression of synaptophysin in cortex, hippocampus and basipodite of the three groups.③Apoptotic cellscalculation of synaptophysin in cortex,hippocampus and basipodite.RESULTS:Totally 24 rats entered the final analysis. ①On the third day and the seventh day,the scores recorded in Walking Test and Balance Test of the treatment group were less than those in the injury group[Walking Test: (7.5±2.5) s,(5.5±2.1) s,(10.5±2.5) s,(8.2±2.5) s. Balance Test:(3.4±0.5)score,(2.5±0.2) score,(5.7±0.2) score,(5.0±0.5) score,P ＜ 0.05-0.01].But the scores recorded in memory test of the treatment group were still more than those in the control group,memory test[(4.9±1.7) s,(6.2±2.3) s,(4.0±1.5) s,(4.4±2.6) s,P ＜ 0.05-0.01]. ②The expression of synaptophysin in cortex,hippocampus and basipodite in the treatment group was still more than that in the injury group(140.36±3.87, 45.52±2.16,31.67±2.35,96.25±2.85,24.35±2.47,20.49±2.08,P ＜ 0.01);The expression of synaptophysin control group was especially more than that in treatment group (162.24±3.52,50.58±2.31,42.69±2.53, P ＜ 0.01).Apoptotic cells calculation of cortex,hippoeampus and basipodite in treatment group was far less than those in injury group,(10.37±2.12)%,(18.39±2.87)%, (12.78±2.45)%,(21.14±4.85)%,(38.57±3.78)%, (21.18±4.59)%,P ＜ 0.01].And apoptotic cells calculation in injury group was more than those in control group [(3.85±2.56)%,(4.96±2.15)%, (3.52±2.17)%,P ＜ 0.01].CONCLUSION:Tacrolimus can facilitate the expression of synaptophysin,refrain from calcineurin involving in the process of transcription-dependent and nontranscription-dependent apoptosis,and can also contribute to the recovery of memory and neural behaviors post trauma.
