Anti-inflammatory and neuroprotective effects of co-ultraPEALut in a mouse model of vascular dementia

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.