Choline alphoscerate and thioctic acid activity on brain injury in spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) represent a model of hypertension and vascular brain injury [1]. Several studies have shown that cerebrovascular changes in SHR may mimic brain vascular disorders of hypertensive individuals. Hypertension represents a risk factor for the development of cerebrovascular disease and cognitive impairment [2] and contributes to the physiopathology of cerebrovascular alterations. This leads to an increased production of reac-tive oxygen species, cholinergic pathways dysfunction, and neuroinfl ammation. In SHR, signifi -cant brain atrophy, a reduction of white matter volumes, and blood-brain barrier (BBB) dys-function correlated with gliosis and neuroinfl ammation.The present study was designed to investigate if treatment with choline alphoscerate (a-GPC) and (+)-thioctic acid [(+)-TIO], alone or in association, could induce neuroprotection in SHR brain. a-GPC is a cholinergic precursor enhancing cholinergic neurotransmission and countering cognitive impairment associated with cerebrovascular damage. (+)-TIO, the natural eutomer of TIO, has been shown to display antioxidant eff ects in the brain.SHR 24-weeks old were treated with a-GPC and (+)-TIO alone or in combination. Age-matched Wistar Kyoto (WKY) rats were used as normotensive controls. Diff erent brain areas were collected for Western blot and immunohistochemistry analysis of neuronal, glial, BBB, and infl ammatory markers.After four weeks of treatment a-GPC and (+)-TIO alone or in association slightly reduced sys-tolic blood pressure values. Western blot and immunohistochemistry showed that a-GPC restored the expression of neuronal nuclei protein. The two compounds alone or in association did not prevent the downregulation of synaptic proteins. a-GPC and (+)-TIO countered astrogliosis and decreased the level of tumor necrosis factor-alpha. An increase of the BBB markers, aquaporin-4 and glucose transport-1, partially restored by the two compounds was noticeable in SHR.Our results indicate that treatment with a-GPC and (+)-TIO elicits a neuroprotective activ-ity. These data may have a pharmacological relevance and suggest that the two compounds, although they are not anti-hypertensive drugs, could represent a new perspective strategy to prevent hypertension-associated cerebrovascular injury.