Abstract
Vascular cognitive impairment (VCI) is the second most common cause of cognitive deficit after Alzheimer’s disease. Since VCI patients represent an important target population for prevention, an ongoing effort has been made to elucidate the pathogenesis of this disorder. In this review, we summarize the information from animal models on the molecular changes that occur in the brain during a cerebral vascular insult and ultimately lead to cognitive deficits in VCI. Animal models cannot effectively represent the complex clinical picture of VCI in humans. Nonetheless, they allow some understanding of the important molecular mechanisms leading to cognitive deficits. VCI may be caused by various mechanisms and metabolic pathways. The pathological mechanisms, in terms of cognitive deficits, may span from oxidative stress to vascular clearance of toxic waste products (such as amyloid beta) and from neuroinflammation to impaired function of microglia, astrocytes, pericytes, and endothelial cells. Impaired production of elements of the immune response, such as cytokines, and vascular factors, such as insulin-like growth factor 1 (IGF-1), may also affect cognitive functions. No single event could be seen as being the unique cause of cognitive deficits in VCI. These events are interconnected, and may produce cascade effects resulting in cognitive impairment.
Highlights
Vascular cognitive impairment (VCI) [1] comprises both subjects with dementia and mild cognitive impairment (MCI)
We analyzed the most important factors contributing to the onset of cognitive deficits in vascular disorders in humans by exploring data from animal models
The animal models of VCI allow understanding of the important molecular mechanisms leading to the cognitive deficits observed in humans
Summary
Many studies have provided new insights into the causes of VCI. VCI is caused by decreased blood supply to the brain [11]. The affected brain regions undergo a neuronal tissue loss which compromises its structure and function and manifests as a cognitive deficit. The causes of this reduced blood flow can be divided into three main groups: ischemic factors, hemorrhagic factors, and other factors affecting functional brain regions [22]
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