Objective To compare the intensity of cognitive impairment and the level of pathological lesion in hippocampus induced by ischemia or chronic stress for a more valuable guidance in the treatment of post-stroke cognitive impairment(PSCI).Methods Forty male adult SD rats were divided medially into 4 groups:control,stress,ischemia and ischemia plus stress.Animals in 3 treatment groups were subjected respectively to an operation of modified selective middle cerebral artery occlusion or a procedure of continuous 3-week chronic unpredictable mild stress or a combined program of the two treatments.Morris water maze was employed to assess hippocampus-dependent learning and memory function and the brain-derived neurotrophic factor(BDNF)expression was detected by immunohistochemical staining in CA3 area and the mRNA amplification through semi-quantitative reverse transcription polymerase chain reaction(RT-PCR).Results Both chronic stressors and ischemia could significantly decrease the learning and memory function in rats like the escape latency in the performance of the Morris water maze test compared with the controL The stress group was related preferentially to a more severe deterioration in the learning function but not statistically in the memory loss as compared to ischemia group.The cognitive function decreased more markedly in rats when suffered the chronic unpredictable mild stresses plus ischemia,In comparison to control,ischemia significantly increased BDNF+ cells in hippocampal CA3 area (27.0 ±2.5 vs 20.1 ±2.1),while stress markedly reduced the expression of BDNF(15.2 ± 1.8 vs 20.1 ±2.1).Their combined effects still statistically led to a reduction in BDNF expression(8.2 ± 1.5,F =52.87,P ＜0.05).The same tendency was found in BDNF mRNA expression.Conclusions Stress may preferentially and powerfully influence hippocampus-dependent cognitive function compared with ischemia and the combination of focal ischemia and stress leads to the most impairments in cognition and hippocampal BDNF expression.Data suggest that more attention should be given to the strategies to increase the resistance to psychosocial stressors and decrease the depressed symptoms for a full PSCI recovery.