Chronic Cerebral Hypoperfusion Induced Synaptic Proteome Changes in the rat Cerebral Cortex

Abstract

Chronic cerebral hypoperfusion (CCH) evokes mild cognitive impairment (MCI) and contributes to the progression of vascular dementia and Alzheimer's disease (AD). How CCH 2 induces these neurodegenerative processes that may spread along the synaptic network and whether they are detectable at the synaptic proteome level of the cerebral cortex remains to be established.In the present study, we report the synaptic protein changes in the cerebral cortex after stepwise bilateral common carotid artery occlusion (BCCAO) induced CCH in the rat. The occlusions were confirmed with Magnetic Resonance Angiography 5 weeks after the surgery.Synaptosome fractions were prepared using sucrose gradient centrifugation from cerebral cortex dissected 7 weeks after the occlusion. The synaptic protein differences between the sham operated and CCH groups were analysed with label free nanoUHPLC-MS/MS.

Stepwise occlusion of the carotid arteries of the rat: MRI assessment of the effect of donepezil and hypoperfusion-induced brain atrophy and white matter microstructural changes

“…This later finding may suggest possible neuronal loss in the dorsal striatum, despite the lack of large ischemic lesions, which is in agreement with the histological findings in this stepwise BCCAo model [ 27 ]. Our VBM result in the cortex is in agreement with the recent proteomics finding of 46 altered protein abundance in the synaptosome fractions of the cerebral cortex 7 weeks after the stepwise BCCAo occlusion, due to the chronic hypoperfusion [ 62 ].…”

“…Alongside previously demonstrated long term cognitive problems [ 30 – 33 ] there is a further progressive decline in the number of microvessels and additional synaptic proteome changes in the cortex detected 7 weeks after the stepwise BCCAo [ 27 , 62 ]. These data suggest, that the stepwise model, while providing less acute effects (e.g., stroke or mortality), induces relevant biochemical changes, e.g.…”

Automated analysis of whole brain vasculature using machine learning

“…Changes in the brain vasculature are a key feature of a large number of diseases effecting the brain. Primary angiopathies, vascular risk factors (e.g., diabetes), traumatic brain injury, vascular occlusion and stroke all affect the brain vascular network and interfere with normal microcirculation and vascular function [1][2][3][4][5] . Alterations of the brain microvasculature are also seen in neurodegenerative diseases, such as Alzheimer's disease, tauopathy and amyloidopathy.…”

The Chinese herb Fructus Broussonetiae aids learning and memory in chronic cerebral hypoperfusion by reducing proinflammatory microglia activation in rats

“…Rats were fed under a standard laboratory condition (12-h light/dark cycle, at 22 ± 2 • C) with free access to water and food. BCCA occlusion surgery (Volgyi et al, 2018) was performed on the rats to induce chronic cerebral hypoperfusion. A ventral midline incision was done on the neck of isoflurane-anesthetized rats (3-5% in 70% nitrogen and 30% oxygen).…”