Effects of different degrees of carotid artery stenosis on cognitive function and neuronal apoptosis of hippocampal CA1 region in rats / 中国脑血管病杂志

ABSTRACT

Objectives To investigate the effects of different degrees of carotid artery stenosis on cognitive function and neuronal apoptosis of hippocampal CA1 region in rats and to analyze the possible mechanisms of cognitive impairment. Methods According to the random number table,50 male Wistar rats were allocated into a sham operation group,a unilateral mild stenosis group,a unilateral moderate stenosis group,a unilateral severe stenosis group,a bilateral mild stenosis group,a bilateral moderate stenosis group, a bilateral severe stenosis group,and a sham operation group. Aneedle-controlled suture method was used to induce a carotid stenosis model with different degrees of stenosis in rats. Water maze was to localize navigation and spatial search test was used to evaluate the cognitive function with different degrees of carotid artery stenosis in rats. Immunohistochemical method was used to observe the numbers of positive cells of P75 neurotrophin receptor (p75NTR),Bax,Bcl-2,neurotrophic factor-3 (NT-3 ),nerve growth factor (NGF)in hippocampal CA1 region under the light microscope. The conditions of neuronal apoptosis were observed. Results In 50 rats,6 died,1 rat in poor health failed to complete the Morris water maze test. The degree of bilateral carotid artery stenosis in 1 rat failed to meet 30%-60% at the same time,they were all removed. The remaining 42 rats were 6 in each group. (1)Compared with the sham operation group,the mean escape latency was prolonged (39 ± 6 s,32 ± 5 s,69 ± 7 s,respectively vs. 23 ± 4 s;all P < 0. 01),and the percentage of swimming distance in the platform quadrant was decreased (35 ± 4%,44 ± 4%,22 ± 5%,respectively vs. 53 ± 7%;all P < 0. 01),and the cognitive function was decreased with the degree of stenosis in the unilateral severe stenosis group,bilateral moderate stenosis group,and bilateral severe stenosis group. Compared with the unilateral severe stenosis group,the mean escape latency was prolonged and the percentage of swimming distance in the platform quadrant was decreased in the bilateral severe stenosis group (P < 0. 01). (2)Compared with the numbers of positive cells of Bax,p75NTR and Bcl-2 (8. 8 ± 3. 1,4. 2 ± 2. 3,and 5. 8 ± 1. 8,respectively)in the sham operation group,the numbers of positive cells of Bax,p75NTR,and Bcl-2 were increased (25. 5 ± 3. 5,11. 0 ± 2. 2,12. 3 ± 2. 7;15. 8 ± 3. 7,8. 9 ± 2. 2, 10. 5 ± 2. 9;and 47. 9 ± 6. 3,24. 7 ± 3. 0,12. 8 ± 2. 5,respectively)in the unilateral severe stenosis group, bilateral moderate stenosis group,and bilateral severe stenosis group (all P < 0. 01). The numbers of Bax and p75NTR positive cells were increased with the degree of stenosis. When the stenosis was severe,the numbers of Bax and p75NTR positive cells were increased in the bilateral severe stenosis group compared with those of the unilateral severe stenosis group (P < 0. 01). The numbers of NGF and NT-3 positive cells in each stenosis group had an increased trend compared with sham operation group,but there were no significant differences (F =1. 034,and 1. 358;P = 0. 420 and 0. 259 respectively). Conclusions Carotid stenosis can cause cognitive disorder in rats,and it is correlated with the degree of carotid stenosis. Ischemia caused neuronal apoptosis in hippocampal CA1 region may be one of the mechanisms of cognitive impairment after carotid artery stenosis in rats.