| Objective:To explore the feasibility of bilateral carotid artery stenosis rats as early rat models of vascular cognitive dysfunction and mild cognitive dysfunction.To study the difference between bilateral carotid artery stenosis and bilateral carotid artery atresia as a model of vascular cognitive dysfunction and the effect of mild hypoxia on the hn RNPA2-GABA_AR-α1 pathway in neurons.Method:In the first part,we choose 4 months old(n=6/11;150±50g),12 months old;(n=6/6;300±50g),18 months old(n=6/7;500±50g)male SD rats.At the same time,a control group of the same age was established in each group,and bilateral carotid artery stenosis was detected on the laser speckle flowmeter.The degree of stenosis was based on a 60±10%decrease in carotid blood flow within 5 minutes after stenosis.At 30 days after operation,the water maze was used to observe the changes of cognitive function after bilateral carotid artery stenosis in rats of various age groups.In the second part,aged(18 months)SD Rats were performed to bilateral CCA stenosis(BCAS)or occlusion(BCAO)or sham operation(Control group).Cerebral blood flow(CBF)in the frontal cortices was measured by Doppler flowmetry.The cognitive function impairment was detected with the Morris Water Maze on the 30th after operation.Cerebral MRI was used by detecting the change of fractional anisotropy(FA)in rats to assess white matter injury on the 30th after operation.Histological studies were performed at 30 days after surgery.Results:In the first part of the experiment,compared with the control group of 18-month-old rats,the results of water maze showed that they had cognitive dysfunction and prolonged escape latency.In the second,the mortality is 11%(30/34)in the BCAS group.At 2 hours,the CBF values(ratio to the preoperative value)decreased significantly in the BCAS and BCAO group.In BCAS groups,the microscopic structure changed slightly after 30 days in the CA1 hippocampus of rats.The difference between the escape latency in the BCAS model and control groups was less significant of that in the model group(P<0.5).Hn RNPA2 found to be significantly declined in the hippocampus of BCAS group rats.The Gabbar-α1 decrease in BCAS group animals compared with control.Fluorescence staining of GFAP showed that the space of injured neurons was filled by stellate neuronal cells in the brain of the BCAS group.This phenomenon is more pronounced in the BCAO group.MRI study in the rat model of the BCAS model revealed the FA valve is slightly lower in hippocampal and cortex,the intense changes were more severe in BCAO rats.Conclusion:Severe bilateral carotid stenosis induced mild cognitive dysfunction slightly cerebral structural change in aged rats.Chronic cerebral hypoperfusion model in this study was established successfully. |
