Spermidine attenuates microglial activation, neuroinflammation, and neuronal injury in rat model of vascular dementia.

Spermidine has been implicated to provide beneficial effects on cognitive function in several model organisms as well as older adults with mild and moderate dementia. Nevertheless, the potential impact of spermidine on learning and memory deficits in vascular dementia (VaD) remains largely unknown. Here, bilateral common carotid artery occlusion (BCCAo) was applied to induce chronic cerebral hypoperfusion in rats. We demonstrated that spermidine therapy improved the spatial learning performance in model animals, accompanied with decreased cerebral histopathologic injury and increased restored myelin basic protein (MBP) expression. Moreover, spermidine suppressed abnormal microglia activation, inhibited the excessive generation of proinflammatory mediators, such as tumor necrosis factor (TNF)α and inducible nitric oxide synthase (iNOS), and increased the anti-inflammatory cytokine transforming growth factor (TGF)β expression in rodent brain following hypoperfusion. Our findings indicated that spermidine alleviated cognitive impairments of rats after VaD-like injury possibly via suppressing microglia-modulated neuroinflammation and neuronal injury. These data may shed light on understanding the pathogenesis of VaD and point to the promising value of spermidine supplementation for cognition improvement.