Preserving Mitochondrial Structure and Motility Promotes Recovery of White Matter After Ischemia

Bastian, Chinthasagar; Day, Jerica; Politano, Stephen; Quinn, John P.; Brunet, Sylvain; Baltan, Selva

doi:10.1007/s12017-019-08550-w

Cited by 6 publications

(1 citation statement)

References 67 publications

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“…WMLs are associated with cognitive dysfunction in VaD patients and involve injury to oligodendrocytes. The pathogenesis of WMLs is associated with ischemic conditions in the brain 232 - 234 . In fact, many studies emphasize the role of damaged BBB in the induction and progression of WMLs 235 - 237 .…”

Section: The Blood-brain Barrier In Health and Diseasementioning

confidence: 99%

Pathophysiology of blood brain barrier dysfunction during chronic cerebral hypoperfusion in vascular cognitive impairment

Rajeev¹,

Fann²,

Dinh³

et al. 2022

Theranostics

102

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The prevalence of cerebrovascular disease increases with age, placing the elderly at a greater lifetime risk for dementia. Vascular cognitive impairment (VCI) encompasses a spectrum of cognitive deficits from mild cognitive impairment to dementia. VCI and its most severe form, vascular dementia (VaD), is becoming a major public health concern worldwide. As growing efforts are being taken to understand VCI and VaD in animal models and humans, the pathogenesis of the disease is being actively explored. It is postulated that chronic cerebral hypoperfusion (CCH) is a major cause of VCI. CCH activates a molecular and cellular injury cascade that leads to breakdown of the blood brain barrier (BBB) and neurodegeneration. The BBB tightly regulates the movement of substances between the blood and the brain, thereby regulating the microenvironment within the brain parenchyma. Here we illustrate how BBB damage is causal in the pathogenesis of VCI through the increased activation of pathways related to excitotoxicity, oxidative stress, inflammation and matrix metalloproteinases that lead to downstream perivascular damage, leukocyte infiltration and white matter changes in the brain. Thus, CCH-induced BBB damage may initiate and contribute to a vicious cycle, resulting in progressive neuropathological changes of VCI in the brain. This review outlines the molecular and cellular mechanisms that govern BBB breakdown during CCH and highlights the clinical evidence in identifying at-risk VCI patients.

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