PROTECTIVE ACITIVITY OF THE CHOLINE CONTAINING PHOSPHOLIPID CHOLINE ALPHOSCERATE, ON CEREBROVASCULAR TREE OF SPONTANEOUSLY HYPERTENSIVE RATS

Since 1980, pre-clinical and clinical evidence, identified the cholinergic system as relevant for learning and memory processes. Based on this hypothesis precursor loading strategies were proposed for countering cognitive impairment occurring in adult-onset dementia disorders. Cholinergic precursors may increase choline availability and acetylcholine synthesis/release in different brain areas. Among compounds of this class, choline alphoscerate (alpha-gliceryl-phosphoryl-choline, GPC) is the most effective in enhancing acetylcholine biosynthesis and release in animal models. This study was designed to assess the effect of long term treatment with GPC on cerebrovascular tree in a model of vascular brain injury represented by spontaneously hypertensive rats (SHR). Male SHR aged 32 weeks and agematched normotensive Wistar-Kyoto (WKY) rats were treated for 4 weeks with GPC (150 mg/kg/day) or vehicle. Wall and lumen area of pial and intracerebral arteries of different brain areas were analyzed by morphometric techniques. Vascular astrocytes, blood brain barrier (BBB) and endothelial markers of inflammation were assessed by immunohistochemistry associated with quantitative analysis. In SHR, no significant changes in the size of perivascular astrocytes were observed compared to WKY rats. The expression of the BBB markers aquaporin-4 and claudin-5 was increased and decreased respectively, in the brain of SHR. In terms of activity on BBB, GPC treatment countered changes of aquaporin-4. Hypertension affected to a different extent endothelial markers and vascular adhesion molecules expression in 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 countered cerebral microanatomical changes occurring in SHR may represent the basis for investigating the activity of the compound in cerebrovascular patients with cognitive dysfunction.