Cholinergic precursors increasing choline availability and acetylcholine synthesis/release may
represent a therapeutic approach for countering 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. This
study was designed to assess if a long-term treatment with GPC modify cerebrovascular components
[perivascular astrocytes, blood-brain barrier (BBB) and microvessels] and endothelial inflammatory
markers expression in spontaneously hypertensive rats (SHR) used as a model of brain vascular injury.
Male SHR aged 32 weeks and age-matched normotensive Wistar-Kyoto rats were treated for 4 weeks with GPC (150
mg/kg/day) or a vehicle. Intracerebral arteries of different brain areas, perivascular astrocytes, BBB and endothelial
inflammatory markers were assessed by quantitative morphological and immunohistochemical techniques. No significant
changes in the size of perivascular astrocytes were observed in SHR versus normotensive Wistar-Kyoto rats, whereas the
expression of the BBB marker aquaporin-4 increased in SHR. This phenomenon was countered by GPC treatment. On the
contrary, GPC has no vasodilator effect on brain micro-vessels. Endothelial markers and vascular adhesion molecules
expression were not homogeneously affected by hypertension and GPC treatment in intracerebral vessels. The observation
that treatment with GPC reversed BBB changes and countered to some extent micro-vessels changes occurring in SHR could
explain data of clinical trials reporting an improvement of cognitive function in subjects suffering from cerebrovascular
disorders and treated with GPC. These preclinical data suggest that the compound could have a cerebrovascular protective
effect deserving a further characterization.
Keywords: Blood-brain barrier, cell adhesion molecules, cerebrovascular tree, choline alphoscerate, spontaneously
hypertensive rats, vascular endothelium.
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