Inflammation and the Link to Vascular Brain Health: Timing Is Brain

Abstract

Inflammation and its myriad pathways are now recognized to play both causal and consequential roles in vascular brain health. From acting as a trigger for vascular brain injury, as evidenced by the coronavirus disease 2019 (COVID-19) pandemic, to steadily increasing the risk for chronic cerebrovascular disease, distinct inflammatory cascades play differential roles in varying states of cerebrovascular injury. New evidence is regularly emerging that characterizes the role of specific inflammatory pathways in these varying states including those at risk for stroke and chronic cerebrovascular injury as well as during the acute, subacute, and repair phases of stroke. Here, we aim to highlight recent basic science and clinical evidence for many distinct inflammatory cascades active in these varying states of cerebrovascular injury. The role of cerebrovascular infections, spotlighted by the severe acute respiratory syndrome coronavirus 2 pandemic, and its association with increased stroke risk is also reviewed. Rather than converging on a shared mechanism, these emerging studies implicate varied and distinct inflammatory processes in vascular brain injury and repair. Recognition of the phasic nature of inflammatory cascades on varying states of cerebrovascular disease is likely essential to the development and implementation of an anti-inflammatory strategy in the prevention, treatment, and repair of vascular brain injury. Although advances in revascularization have taught us that time is brain, targeting inflammation for the treatment of cerebrovascular disease will undoubtedly show us that timing is brain.

Induced Inflammatory and Oxidative Markers in Cerebral Microvasculature by Mentally Depressive Stress

“…Animal experiments have proved excess inflammatory responses and oxidative injuries in cardiovascular systems from mental stress. Endothelial inflammation is noted to be the initial step in atherosclerosis [ 40 , 41 ], and cerebrovascular inflammation has been found to play an important role in intracranial atherosclerosis [ 29 , 42 , 43 ] and CVD [ 44 , 45 ]. Studies have confirmed the involvement of inflammatory mediators in the early proatherogenic processes, such as upregulation of adhesion molecules and highly activated inflammatory responses on endothelial cells [ 46 ].…”

Single-nucleus RNA sequencing of midbrain blood-brain barrier cells in schizophrenia reveals subtle transcriptional changes with overall preservation of cellular proportions and phenotypes

“…In addition, increased expression of pro-inflammatory cytokines, such as SERPINE3, IL1B and IL6, was observed in the midbrain of patients with schizophrenia [ 3 – 5 ]. Increased chronic inflammation may have detrimental consequences on midbrain vasculature, either during the increased inflammatory state, or once inflammation has subsided [ 6 ]. On the other hand, intrinsic alterations in the brain vasculature of patients with schizophrenia may impair toxin efflux and favor the ingression of toxic material into the central nervous system (CNS), leading to neuroinflammation (discussed in [ 7 – 9 ]).…”

Nerolidol Attenuates Cerebral Ischemic Injury in Middle Cerebral Artery Occlusion-Induced Rats via Regulation of Inflammation, Apoptosis, and Oxidative Stress Markers

“…Numerous animal and human studies have reported increased levels of TNF-α during ischemic conditions. 51, 52 Antiinflammatory properties of nerolidol inhibited the COX-2, PGE-2, and NFκB signalling proteins thereby decreasing the levels of proinflammatory cytokines TNF-α, IL-1β, and IL-6 in MCAO-performed rats. It also increased the levels of anti-inflammatory cytokine IL-10 in MCAO-performed rats.…”