Compound Congrong Yizhi capsule partially remodels the fronto-retrosplenial-hippocampal memory circuit in vascular dementia rats

Vollständiger Abstract

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Background Progressive cognitive impairment in vascular dementia (VaD) is increasingly linked to brain network disruption, or “disconnection syndrome.” Although Compound Congrong Yizhi Capsule (CCYC), a marketed Chinese patent medicine approved in China for vascular cognitive disorders, has been studied in terms of therapeutic efficacy and molecular targets, these approaches do not directly explain how this multi-target intervention modulates brain functional organization. Resting-state functional magnetic resonance imaging (rs-fMRI) enables in vivo characterization of BOLD-based brain network functional phenotypes. Here, we used rs-fMRI to investigate the effects of CCYC in a rat model of VaD. Methods VaD was induced by permanent bilateral common carotid artery occlusion (BCCAO) in rats. CCYC was administered by gavage for 6 weeks. Spatial navigation and memory retention were assessed using the Morris water maze (MWM). Resting-state fMRI was acquired on a 9.4 T scanner and analyzed using regional activity metrics, behavioral correlations, functional connectivity, and graph theoretical analyses. Results VaD rats showed abnormal regional activity in the frontal cortex, retrosplenial cortex, and hippocampal system, which were associated with impaired MWM performance. They also exhibited disrupted connectivity within the fronto-retrosplenial-hippocampal memory circuit, particularly between prefrontal/cingulate and retrosplenial-hippocampal regions. CCYC treatment was associated with partial normalization of these regional and circuit-level abnormalities. Graph theoretical analyses further showed partial improvement in whole-brain topological organization and nodal properties after CCYC treatment. These findings do not establish anatomical restoration of the underlying white matter tracts. Conclusion CCYC may ameliorate VaD by modulating a systems-level neuroimaging phenotype centered on the fronto-retrosplenial-hippocampal memory circuit.