Neuroinfl ammation on hippocampus of hypertensive rats: possible protective activity of antioxidant and cholinergic cognitive enhancing compounds

Several well-known risk factors, including hypertension, obesity, high cholesterol, dyslipidemia, and diabetes, are recognized in the pathogenesis of cerebrovascular disease and cognitive impairment1 . Arterial hypertension is accompanied by high levels of cellular reactive oxygen species, cholinergic pathways dysfunction, and neuroinflammation. These changes contribute to the development of brain disorders 2. In spontaneously hypertensive rats (SHR), brain white matter atrophy and neurovascular unit (NVU) dysfunction accompanied by gliosis and neuroinfl ammation are noticeable. Our study has investigated if long-term treatment with CDP-Choline (CDP) and (+)-thioctic acid (TIO), alone or in association, could induce neuroprotection. CDP shows potential nootropic activity, increases acetylcholine synthesis/release, and is involved in preserving cell membrane phospholipids. TIO acts as a free radical scavenger, repairing oxidative damage and regenerating endogenous antioxidants. 24-week-old SHR rats were treated for four weeks with CDP and TIO alone or in combination. Wistar Kyoto rats were used as a normotensive reference. Western blot (WB) and immunohistochemistry (IHC) of neuronal, glial, and infl ammatory markers were performed in the hippocampus as the main brain area correlated with cognitive functions. Treatment with CDP and TIO alone or in association slightly decreased systolic blood pressure. WB and IHC results showed that CDP and TIO countered gliosis and microglial activation, decreased the level of interleukin-1 beta and tumor necrosis factor-alpha possibly related with modulation of alpha-7 nicotinic acetylcholine receptor. Our fi ndings can contribute to better defi ning the role of the infl ammatory processes of NVU in brain disorders characterized by vascular impairment. Moreover, the use of cholinergic neurotransmission enhancers associated with an antioxidant molecule could represent a therapeutic strategy worth to be investigated in further preclinical and clinical studies.