Molecular dialogs between the ischemic brain and the peripheral immune system: Dualistic roles in injury and repair

Abstract

Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialogue between the brain and peripheral immune system show promise as potential novel treatments for stroke.

Endothelium-targeted overexpression of heat shock protein 27 ameliorates blood–brain barrier disruption after ischemic brain injury

“…Third, the excessive infiltration of peripheral immune cells into the postischemic brain may produce an unfavorable microenvironment that hinders brain repair processes. However, it is widely accepted that neurovascular remodeling may be facilitated by infiltrated leukocytes during the poststroke recovery phase (26). Thus, a complete blockage of immune cell infiltration could be harmful for brain recovery.…”

“…Leukocytes that infiltrate through the impaired BBB play an important role in the development of permanent neurovascular injury and neurological deficits after I/R (26). Blood neutrophils and macrophages carry proinflammatory mediators into the brain, such as gelatinase Fig.…”

Lymphocytopenia Is an Independent Predictor of Unfavorable Functional Outcome in Spontaneous Intracerebral Hemorrhage

“…Being aware that these associations still may reflect an epiphenomenon of variables and a bias in terms of comorbidity, a subset of patients with ICH-that is, those patients without LOA who develop lymphocytopenia-however, may represent a high-risk population potentially benefitting from pharmacological interventions. 3,[25][26][27][28] Such therapeutical approaches may include intensified screening for infections and more liberal use of anti-infective agents. 29,30 Given various limitations of this study, above findings need to be interpreted with caution.…”

Potential of Anthocyanin From Purple Sweet Potato (Ipomoea batatas) To Increase BDNF Level and VEGF Expression in The Cerebellum of Ischemic Stroke Rats

“…In vitro studies demonstrate the ability of microglial cells, cerebral endothelial cells and astrocytes to express and secrete BDNF when the brain is exposed to ischemic conditions [21]. BDNF may improve neurogenesis after ischemic injury by activating neural and pro-neurogenic pathways PI3K/Akt and MAPK [13].…”

“…In contrast, the hypoxia caused by blood flow blocking triggers a protein stress to form Heat Shock Protein-90 (HSP-90) [12]. This protein stimulates BDNF activation through activation of protein kinase B and Adenine Monophosphate-Activated Protein Kinase (AMPK)/ERK [13]. The formation of Brain-Derived Nuclear Factor (BDNF) is started with modification of phosphorylation protein component at synapses which modify a translation activity in the transcription process.…”