Astrocytic Sonic Hedgehog Alleviates Intracerebral Hemorrhagic Brain Injury via Modulation of Blood-Brain Barrier Integrity

Xing, Gebeili; Zhao, Tianman; Zhang, Xiyue; Li, Xiuping; Cui, Pan; Li, Minshu; Li, Daojing; Zhang, Nan; Jiang, Wei

doi:10.3389/fncel.2020.575690

Cited by 26 publications

(7 citation statements)

References 68 publications

(78 reference statements)

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“…After CNS injury, the expression of Shh is increased in astrocytes. The administration of exogenous Shh attenuates BBB destruction, while the application of the Shh inhibitor jervine exerts the opposite effects in mice with TBI (Xing et al, 2020 ; Michinaga et al, 2021 ). In the mouse SCI model, Shh/Gli1 signaling is induced in RAs and plays an important role in the permeability of BSCB and locomotor recovery after SCI (Yue et al, 2020 ).…”

Section: Reactive Astrocytesmentioning

confidence: 99%

Reactive Astrocytes in Central Nervous System Injury: Subgroup and Potential Therapy

Zhang

Ning

2021

Front. Cell. Neurosci.

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Traumatic central nervous system (CNS) injury, which includes both traumatic brain injury (TBI) and spinal cord injury (SCI), is associated with irreversible loss of neurological function and high medical care costs. Currently, no effective treatment exists to improve the prognosis of patients. Astrocytes comprise the largest population of glial cells in the CNS and, with the advancements in the field of neurology, are increasingly recognized as having key functions in both the brain and the spinal cord. When stimulated by disease or injury, astrocytes become activated and undergo a series of changes, including alterations in gene expression, hypertrophy, the loss of inherent functions, and the acquisition of new ones. Studies have shown that astrocytes are highly heterogeneous with respect to their gene expression profiles, and this heterogeneity accounts for their observed context-dependent phenotypic diversity. In the inured CNS, activated astrocytes play a dual role both as regulators of neuroinflammation and in scar formation. Identifying the subpopulations of reactive astrocytes that exert beneficial or harmful effects will aid in deciphering the pathological mechanisms underlying CNS injuries and ultimately provide a theoretical basis for the development of effective strategies for the treatment of associated conditions. Following CNS injury, as the disease progresses, astrocyte phenotypes undergo continuous changes. Although current research methods do not allow a comprehensive and accurate classification of astrocyte subpopulations in complex pathological contexts, they can nonetheless aid in understanding the roles of astrocytes in disease. In this review, after a brief introduction to the pathology of CNS injury, we summarize current knowledge regarding astrocyte activation following CNS injury, including: (a) the regulatory factors involved in this process; (b) the functions of different astrocyte subgroups based on the existing classification of astrocytes; and (c) attempts at astrocyte-targeted therapy.

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Section: Reactive Astrocytesmentioning

confidence: 99%

Reactive Astrocytes in Central Nervous System Injury: Subgroup and Potential Therapy

Zhang

Ning

2021

Front. Cell. Neurosci.

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“…Although MMP-9, which has a destructive effect in the early phase, is upregulated in the peri-infarct cortex 7-14 days after stroke and shows a angiogenesis-promoting function (147). Moreover, sonic hedgehog released from astrocytes promotes the upregulation of tight junction proteins between capillary endothelial cells to promote the restoration of BBB integrity (148). Thirdly, glial cells play an important role in promoting synaptogenesis and plasticity.…”

Section: Glial Cell-related Neural Repair After Strokementioning

confidence: 99%

Crosstalk Between the Oxidative Stress and Glia Cells After Stroke: From Mechanism to Therapies

et al. 2022

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Stroke is the second leading cause of global death and is characterized by high rates of mortality and disability. Oxidative stress is accompanied by other pathological processes that together lead to secondary brain damage in stroke. As the major component of the brain, glial cells play an important role in normal brain development and pathological injury processes. Multiple connections exist in the pathophysiological changes of reactive oxygen species (ROS) metabolism and glia cell activation. Astrocytes and microglia are rapidly activated after stroke, generating large amounts of ROS via mitochondrial and NADPH oxidase pathways, causing oxidative damage to the glial cells themselves and neurons. Meanwhile, ROS cause alterations in glial cell morphology and function, and mediate their role in pathological processes, such as neuroinflammation, excitotoxicity, and blood-brain barrier damage. In contrast, glial cells protect the Central Nervous System (CNS) from oxidative damage by synthesizing antioxidants and regulating the Nuclear factor E2-related factor 2 (Nrf2) pathway, among others. Although numerous previous studies have focused on the immune function of glial cells, little attention has been paid to the role of glial cells in oxidative stress. In this paper, we discuss the adverse consequences of ROS production and oxidative-antioxidant imbalance after stroke. In addition, we further describe the biological role of glial cells in oxidative stress after stroke, and we describe potential therapeutic tools based on glia cells.

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“…Various AC proteins such as aquaporin-4 (Aqp4) and the Kir4.1 potassium channel localize to the end-foot membrane to regulate water homeostasis ( Engelhardt and Liebner, 2014 ; Figure 1A ). ACs function in BBB maintenance and induce the barrier properties of BMECs through various pathways such as Wnt ( Guérit et al, 2021 ), Shh ( Xing et al, 2020 ), and VE-PTP-dependent restoration of Tie2 signaling ( Gurnik et al, 2016 ). The interaction between ACs and BMECs not only improves AC differentiation via the secretion of leukemia inhibitory factor 1 (LIF1) by BMECs but also maintains the development of the BBB through VE-PTP-dependent restoration of Tie2 signaling ( Liebner et al, 2018 ).…”

Section: The Structure and Biomechanisms Of Blood–brain Barriermentioning

confidence: 99%

New insight into neurological degeneration: Inflammatory cytokines and blood–brain barrier

Yang

Ran²,

Li³

et al. 2022

Front. Mol. Neurosci.

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Neurological degeneration after neuroinflammation, such as that resulting from Alzheimer’s disease (AD), stroke, multiple sclerosis (MS), and post-traumatic brain injury (TBI), is typically associated with high mortality and morbidity and with permanent cognitive dysfunction, which places a heavy economic burden on families and society. Diagnosing and curing these diseases in their early stages remains a challenge for clinical investigation and treatment. Recent insight into the onset and progression of these diseases highlights the permeability of the blood–brain barrier (BBB). The primary factor that influences BBB structure and function is inflammation, especially the main cytokines including IL-1β, TNFα, and IL-6, the mechanism on the disruption of which are critical component of the aforementioned diseases. Surprisingly, the main cytokines from systematic inflammation can also induce as much worse as from neurological diseases or injuries do. In this review, we will therefore discuss the physiological structure of BBB, the main cytokines including IL-1β, TNFα, IL-6, and their mechanism on the disruption of BBB and recent research about the main cytokines from systematic inflammation inducing the disruption of BBB and cognitive impairment, and we will eventually discuss the need to prevent the disruption of BBB.

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Astrocytic Sonic Hedgehog Alleviates Intracerebral Hemorrhagic Brain Injury via Modulation of Blood-Brain Barrier Integrity

Cited by 26 publications

References 68 publications

Reactive Astrocytes in Central Nervous System Injury: Subgroup and Potential Therapy

Reactive Astrocytes in Central Nervous System Injury: Subgroup and Potential Therapy

Crosstalk Between the Oxidative Stress and Glia Cells After Stroke: From Mechanism to Therapies

New insight into neurological degeneration: Inflammatory cytokines and blood–brain barrier

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