Abstract
Vascular dementia (VaD), the second most common cause of cognitive impairment in the population, is a disease that results from reduction in regional cerebral blood flow and involves oxidative stress and inflammation. Co-ultramicronized PEALut (co-ultra PEALut) is a new compound with beneficial effects, which include anti-inflammatory and antioxidant properties. Recently, co-ultraPEALut has been shown to exhibit neuroprotective effects in models of Parkinson’s disease, cerebral ischemia and Alzheimer’s disease. However, its effects on VaD remain unknown. Therefore, the purpose of the present study was to highlight the potential neuroprotective actions of co-ultraPEALut containing N-palmitoylethanolamine (PEA) and the antioxidant flavonoid luteolin (Lut) (10:1 by mass) in a mouse model of VaD induced by bilateral carotid arteries occlusion. At 24 h after VaD induction, mice were orally treated with 1 mg/kg co-ultraPEALut daily for 15 days. On the 15th day, brain tissues were processed for histological, immunohistochemical, Western blot, and immunofluorescent analysis. Our results clearly demonstrate that co-ultraPEALut improved learning, memory ability, locomotor activity, and the reciprocal social interaction. In addition, the mice subjected to VaD and treated with the co-ultraPEALut showed a reorganization of CA1 and CA3 regions of the hippocampus and restored the number of hippocampal neurons as evidenced by NeuN expression, a specific marker of neurons. Furthermore following carotid arteries ligation, mice treated with co-ultraPEALut showed a modification of proinflammatory, proapoptotic proteins and of oxidative stress as evidenced by the expression of IκB-α, NF-κB p65, Bax, Bcl-2, inducible nitric oxide synthase, and cyclooxygenase-2. In order, co-ultraPEALut treatment restored VaD-induced loss of brain-derived neurotrophic factor and neurotrophins 3 (NT-3) expression in mice. These results confirmed that the neuroprotective effects of co-ultraPEALut were associated with its anti-inflammatory and antioxidant properties.
Highlights
An estimated 36 million people worldwide were afflicted with dementia
To explore molecular mechanism underlying of the neuroprotective effect of co-ultraPEALut, we evaluated, in the mice hippocampal CA1 and CA3 regions, two proteins implicated in apoptotic death using immunohistochemical staining
The growing importance of dementias phenomenon imposes an increasingly urgent need to gain more knowledge about this group of diseases, the techniques that allow earlier diagnosis and accurate, and primarily on preventive and therapeutic strategies acting on the mechanisms that underlie neuropathological cascade that leads to the death of neurons and the consequent progressive loss of cognitive abilities [43]
Summary
Among the subtypes of dementia, vascular dementia (VaD) is accounting for 15 to 20% of all cases of dementia [1]. It results from a variety of causes, including cerebrovascular dysfunction. After blocking of the carotid arteries, a significant reduction in regional cerebral blood flow causes deprivation of oxygen and glucose. These events lead to the activation of neuroinflammation, oxidative, and nitrosative stress that are the main causes of VaD [9, 10]. A lot of oxygen free radicals and their derivatives are generated after stroke, including superoxide anions ( ) O2− , hydrogen peroxide (H2O2), and hydroxyl radicals (⋅OH)
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