title: Cerebrovascular and blood-brain barrier morphology in spontaneously hypertensive rats: effect of treatment with choline alphoscerate.
abstract: 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.
authors.affiliation: University of Camerino, School of Pharmacy, Human Anatomy Section, Via Madonna delle Carceri 9, 62032 Camerino (MC), Italy. khosrow.tayebati@unicam.it.
authors.forename: Seyed Khosrow
authors.initials: SK
authors.lastname: Tayebati
authors.forename: Francesco
authors.initials: F
authors.lastname: Amenta
authors.forename: Daniele
authors.initials: D
authors.lastname: Tomassoni
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D002561:Cerebrovascular Disorders / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D062507:Claudin-5 / Q000378:metabolism; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005997:Glycerylphosphorylcholine / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009929:Organ Size; D019007:P-Selectin / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D062507:Claudin-5; C491510:Cldn5 protein, rat; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D019007:P-Selectin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D005997:Glycerylphosphorylcholine