CEREBROVASCULAR PROTECTION BY CHOLINE ALPHOSCERATE IN SPONTANEOUSLY HYPERTENSIVE RATS: A MICROANATOMICAL STUDY

Introduction: It has been hypothesized that cholinergic precursors increasing choline availability and acetylcholine synthesis/release may counter cognitive impairment occurring in adult-onset dementia disorders. Choline alphoscerate (alpha-gliceryl-phosphoryl-choline, GPC) is among cholinergic precursors the most effective in enhancing acetylcholine biosynthesis and release in animal models. Objective: The present study has assessed if long term treatment with GPC has a cerebroprotective effect on brain injury of vascular origin. Methods: Analysis was made on spontaneously hypertensive rats (SHR) used as animal model of brain vascular injury. Male SHR aged 32 weeks and age-matched normotensive Wistar–Kyoto (WKY) rats were treated for 4 weeks with GPC (150 mg/kg/day) or vehicle. On pial and intracerebral arteries of different brain areas, vascular astrocytes, blood brain barrier (BBB) and endothelial markers were assessed by neuromorphological and immunohistochemical techniques associated with quantitative analysis. Results: No significant changes in the size of perivascular astrocytes were observed in SHR compared to WKY, whereas the expression of the BBB marker aquaporin-4 decreased in SHR. This phenomenon was countered by GPC treatment. Endothelial markers and vascular adhesion molecules expression were not homogeneously affected by hypertension in both pial and intracerebral vessels. In SHR a decrease of vascular endothelial growth factors sensitive to GPC treatment was noticeable. The observation that treatment with -GPC reversed cerebral microanatomical changes occurring in SHR is consistent with data of clinical trials reporting an improvement of cognitive function in subjects suffering from cerebrovascular disorders. Conclusion: These preclinical data suggest a re-evaluation of GPC activity in controlled clinical studies in cerebrovascular patients with cognitive dysfunction.