ACTIVITY OF CHOLINE ALPHOSCERATE ON CEREBROVASCULAR MORPHOLOGY AND INFLAMMATORY MARKERS IN SPONTANEOUSLY HYPERTENSIVE RATS

The effect of cholinergic precursors on choline availability and acetylcholine synthesis/release is established. It is thought that this increase contributes to counter cognitive impairment occurring in adult-onset dementia disorders. Choline alphoscerate (alpha-gliceryl-phosphoryl-choline, GPC) is among cholinergic precursors so far available the most effective in enhancing acetylcholine biosynthesis and release in animal models. Chronic brain vascular injury is a severe risk factor of cerebral dysfunction. White matter lesions represent relevant and early consequences of cerebrovascular injury. Cerebral hypoperfusion can induce small vessel disease (SVD) and is linked to the development of white matter lesions. Brain hypoperfusion and white matter lesions correlate with the development of cognitive impairment in Alzheimer’s disease (AD) or vascular dementia (VaD). The present study has assessed if long term treatment with GPC has a cerebroprotective effect on brain injury of vascular origin in the rat. Analysis was made on spontaneously hypertensive rats (SHR used as an 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. No significant changes in the size of perivascular astrocytes were found in SHR compared to WKY rats, 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 (ICAM, VCAM, PECAM, and P-selectine) expression were not homogeneously affected by hypertension in both pial and intracerebral vessels. 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. These preclinical results suggest a re-evaluation of GPC activity in cerebrovascular patients with cognitive dysfunction.