Study Of Behavior, Pathology And Related Mechanism In Vascular Dementia Rats Induced By Chronic Cerebral Ischemia

Objective:To investigate dynamic changes of hippocampal IGF-1/IGF-1R signaling and learning and memory ability in vascular dementia (VaD) rats induced by chronic cerebral ischemia and probe the possible pathogenesis of VaD.Methods:The first part of the experiment:VaD model was established by using permanent occlusion of bilateral common carotid arteries (2-VO). At1,2and4months after operation, Morris water maze test was used to evaluate learning and memory ability, HE staining was used to observe the morphology changes of hippocampal neurons. The second part of the experiment:VaD model was established by using permanent occlusion of bilateral common carotid arteries (2-VO). At1,2and4months after operation, ELISA was used to detect the concentrations of IGF-1, IGF-IR, Akt and p-Akt in hippocampus. Western blot was also used to detect changes of Akt and p-Akt at protein level in hippocampus. Quantitative PCR was used to detect changes of IGF-1gene expression in hippocampus.Results:Compared with controls, learning and memory functions was obviously impaired from1month after2-VO. The escape latencies in2-VO1month group were all longer than the sham (p<0.05, p<0.01), and the time spent in target quadrant at the final day was (22.67±1.96) s, which was significantly lower than that of the sham (30.99±2.87)s (p<0.01). These impairments were further deteriorated with the prolongation of2-VO treatment. The injury of pyramidal cells in hippocampal CA1region in model group gradually aggratated with increased duration of2-VO treatment. ELIS A results indicated that protein expression of IGF-1and p-Akt in hippocampus in2-VO lmonth group [(0.09±0.03) ng/mg and (12.50±1.40) pg/mg, respectively] was significantly lower than that of sham operation group [(0.18±0.04) ng/mg and (17.74±1.67) pg/mg, respectively](p<0.01), and lasted to4months after2-VO. There was not obviously changes of IGF-1R and total Akt protein expression (p>0.05). Western Blot results also demonstrated that compared with controls, p-Akt expression were significantly decreased in hippocampus of2-VO rats (p<0.01), however, changes of total Akt levels were not significant (p>0.05). Quantitative PCR results indicated that compared with controls, IGF-1gene expression were significantly decreased in hippocampus of2-VO rats (p<0.01).Conclusion:Permanent occlusion of bilateral common carotid arteries (2-VO) may lead to persistent learning and memory functions impairments. Down-regulation of IGF-1/IGF-IR signaling in the rat hippocampus may be one of the pathogenesis of VaD.