Establishment And Evaluation Of Mice Models Of Post-stroke Depression

Objective: To observe the post-stroke depression(PSD) behaviors after combined use of spatial restraint stress and middle cerebral artery occlusion, and explore the optimal condition at this model. We further detect various measures of post-stroke depression. It is ideal for the investigation of the mechanisms and potential therapies of PSD.Methods: Following 3 days of MCAO,male ICR mice were randomly assigned to different experimental groups: Sham group(Sham), stress-alone group(Stress); ischemia-reperfusion group(IR), ischemia-reperfusion + stress group(SIR). Mice were placed into a well-ventilated 50-ml centrifuge tube 2 h per day. We establish post-stroke depression model by MCAO and spatial restraint stress. After different ischemic time, we recorded the survival rate and nerve function scores of mice. And we observed the depression-like symptoms in SIR group by forced swimming test(FST), tail suspension test(TST) and sucrose preference test. Prognosis of mice was observed by grip-traction test and foot-fault test. HPLC was used to measure the contents of monoamine neurotransmitters including serotonin(5-HT), dopamine(DA). We also measured the brain-derived neurotrophic factor(BDNF) and serum cortisol by ELISA. At last,mice were received(i.p.) imipramine at a 20mg/kg of body weight dose or normal saline. Two weeks later, the change of behaviors was recorded by FST and TST, while the changes of 5-HT and serum cortisol were also detected by ELISA kits.Results: Our results showed that the ischemia time(70 minutes) resulted in higher mortality, and, significant differences in depression-like symptoms can be found in 50 minutes at fourth week. Therefore, 60 minutes of MCAO was chosen to establish the PSD mouse model and used in the following experiments. After spatial restraint stress for 1 week, we found significant differences in depressive performance on sucrose preference test and FST. At second week, we could find significant differences on all the 3 tests(FST, TST and sucrose preference test). At foot-fault test, we found that the number of foot-faults was significantly increased. We found the shorter hanging time at grip-traction test. Body weight, serotonin and dopamine levels were significantly decreased in SIR group. We also found the increased levels of serum cortisol. Finally, after two weeks of treatment, imipramine could attenuate depressive behaviors(FST, TST), increase body weights, recover brain serotonin levels, and significantly decrease serum cortisol levels in PSD mice.Conclusions: Our post-stroke depression mice model could simulate the patient’s symptoms, such as hemiplegic. The behaviors are relatively stable. The levels of 5-HT and DA were significantly decreased in brain tissue. And the content of serum cortisol was increased. The known antidepressant imipramine can resume depression-like behaviors. This model represents an ideal model for studying the mechanisms of PSD and future therapies of PSD.