Establishment and Evaluation of Mouse Models of Chronic Cerebral Ischemia with Qixuxueyu(气虚血瘀)Syndrome
Objective:To establish,characterize,and evaluate the mouse models of Qixuxueyu(气虚血瘀)syndrome.Methods:Three models were established by bilateral common carotid artery occlusion(BCCAO)combined with systemic hypotension surgery,sleep deprivation(SD),and BCCAO combined with systemic hypotension surgery and SD(CCI),respectively.The grip strength test,tongue imaging,open field test,novel object recognition test,and Barnes maze test were carried out to compare the similarity of the three models with the clinical signs of Qixuxueyu syndrome.Nissl staining and Luxol Fast Blue(LFB)staining were employed to detect hippocampal neuronal damage and myelin sheath le-sions,respectively.Transmission electron microscopy was employed to examine myelin ultrastructure and myelin loss,and functional MRI to detect functional connectivity between related brain regions.Results:BCCAO combined with systemic hypotension surgery significantly re-duced cerebral blood flow,causing chronic cerebral ischemia in mice.However,this model and the SD model could not fully simulate the clin-ical symptoms of Qixuxueyu syndrome.The CCI model showed significantly weakened forelimb grip strength,a dark tongue,reduced spontane-ous activity,recognition ability,and memory,which indicated that the model could replicate the clinical characteristics of Qixuxueyu syn-drome.LFB staining revealed obvious pathological damage to the myelin sheath in areas such as the corpus callosum and striatum,and elec-tron microscopy confirmed the presence of obvious demyelination.Functional MRI results showed that the functional connectivity between brain regions related to memory,somatic movement,and sensorimotor function was significantly weakened,which was consistent with the afore-mentioned characteristics of Qixuxueyu.Conclusion:The CCI model closely aligns with the clinical signs of Qixuxueyu syndrome.This model is simple to prepare and minimally invasive to animals and results in clear pathological damage.It can be used for in-depth exploration of the pathological mechanisms of brain diseases caused by Qixuxueyu and provide a model basis for the development of related pharmaceuticals.
Qixuxueyu(气虚血瘀)syndromeChronic cerebral ischemiaMyelin damageFunctional connectivity of the brain
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