Résumé
Objective To observe the effect of ADM3100 on angiogenesis in rat models of cerebral chronic hypoperfusion (CCH) and its mechanism.Methods Thirty-six healthy female SD rats,weighting 200-250 g,were randomly divided in normal control group,CCH+AMD3100 group and CCH+saline group (n=12);rats in the CCH+AMD3100 group and CCH+saline group underwent end-to-side anastomosis between the left distal external jugular vein (EJV) and the ipsilateral common carotid artery,followed by ligation of the right vein draining the transverse sinus and bilateral external carotid arteries,and then,they were received intraperitoneal injection of 5 mg/ (kg·d) ADM3100 and physiological saline,respectively,for a consecutive 30 d.Rats were then scarified;microvessel density (MVD) was assessed based on immunohistochemistry of CD34,numbers of CXCR4 and CD45 double positive cells were confirmed by double immunofluorescence,and matrix metalloproteinases-9 (MMP-9) was evaluated by Western blotting.Results MVD was 61.82±19.83/mm2,89.50±23.61/mm2 and 121.70 ±31.12/mm2 in the normal control group,CCH+AMD3100 group and CCH+saline group,respectively;numbers of CXCR4 and CD45 double positive cells were 3.47±2.63,7.58±4.49 and 12.33± 6.11 per high power field (×200) in normal control group,CCH+AMD3100 group and CCH+saline group,respectively;significant differences between groups were noted (P＜0.05).As compared with the expression of MMP-9 in the normal control group,that in the CCH+AMD3100 group and CCH+saline group was significantly increased (0.009±0.003,0.151 ±0.058 and 0.325 ±0.068,P＜0.05).As compared with CCH+saline group,CCH+AMD3100 group had significantly smaller MVD and numbers of CXCR4 and CD45 double positive cells and lower MMP-9 level (P＜0.05).Conclusion AMD3100 will decrease angiogenesis in rat models of cerebral chronic hypoperfusion,which may be associated with inhibiting CXCR4+ CD45+ cells infiltration into cerebral tissue by blocking stromal cells-derived factor-1 α/CXCR4 signaling.
Résumé
BACKGROUND: Impairment of cognitive function is often present in patients with carotid artery stenosis but the details of this dysfunction have rarely been reported. Our purpose was to elucidate the cognitive dysfunction in patients with unilateral severe carotid stenosis using comprehensive neuropsychological testing, and also to identify the specific underlying clinical and radiological factors. METHODS: We analyzed the results of neuropsychological testing, the clinical history, and MR findings in 16 consecutive patients with angiographically proven severe (70-99%) stenosis of the extra cranial internal carotid artery (ICA). Cognitive functions were examined using the Seoul Neuropsychological Screening Battery and the Neglect Battery. We excluded patients with cortical infarction and those with contra lateral ICA occlusion or severe stenosis. RESULTS: Our comprehensive neuropsychological testing revealed obvious cognitive deficits in all patients with unilateral severe ICA stenosis, the most common being frontal executive impairment. The mean cognitive score on the memory test was also significantly lower in patients with symptomatic ICA stenosis than in asymptomatic patients (29.33+/-10.98, mean+/-SD, p < 0.05). The total score on the global cognitive test was significantly lower in patients with an ischemic lesion on MRI than in no lesion patients (113.23+/-34.78, p < 0.05). The presence of symptoms related to the ICA stenosis was related to cognitive dysfunction even when there were no ischemic lesions on MRI. SPECT revealed ipsilateral cortical hypoperfusion in 9 of 12 patients (75%). CONCLUSIONS: Cognitive deficits are common in patients with unilateral severe ICA stenosis. Our findings suggest that an additional mechanism beyond the structural lesion such as chronic hypoperfusion may affect cognitive function in patients with high-grade ICA stenosis.