CEREBROLYSIN AMELIORATES NEUROCOGNITIVE IMPAIRMENT AND REDUCES INFLAMMATION IN A MURINE MODEL OF VASCULAR DEMENTIA

초록

Background and Aims: Vascular dementia (VaD) is a significant contributor to cognitive decline following stroke and cerebrovascular disease. Currently, therapeutic options for VaD remain limited. Cerebrolysin, a neuropeptide preparation with neurotrophic properties, has shown promise in preclinical studies of neurodegenerative disorders. This study aimed to evaluate the therapeutic potential of Cerebrolysin in a murine model of VaD. Methods: We induced VaD in male C57BL/6 mice (3 months old) via bilateral common carotid artery stenosis (BCAS) using microcoils. After 30 days, mice were treated with Cerebrolysin (2 mg or 10 mg, intraperitoneally) or saline (control) daily for 15 days. Neurocognitive function was assessed using open field, Y-maze, and passive avoidance tests. Brain tissues were analyzed by immunohistochemistry for myelin basic protein (MBP), ionized calcium-binding adapter molecule 1 (IBA-1), and glial fibrillary acidic protein (GFAP) to evaluate white matter integrity and neuroinflammation. Results: BCAS mice treated with Cerebrolysin, particularly at the 10 mg/mL dose, exhibited improved performance in behavioral tests, indicating enhanced working memory and cognitive function. Immunohistochemical analysis revealed that Cerebrolysin treatment significantly increased MBP expression in the corpus callosum, suggesting improved white matter integrity. Furthermore, Cerebrolysin reduced the expression of IBA-1 and GFAP in the hippocampus, indicating a reduction in microglial activation and astrocyte reactivity, respectively. Conclusions: Cerebrolysin demonstrates therapeutic potential for VaD by improving neurocognitive function, promoting white matter integrity, and reducing neuroinflammation in a BCAS-induced VaD mouse model. These findings suggest that Cerebrolysin may be a promising therapeutic agent for VaD and warrant further investigation in clinical trials.