Endothelin ETB Receptor-Mediated Astrocytic Activation: Pathological Roles in Brain Disorders

In brain disorders, reactive astrocytes, which are characterized by hypertrophy of the cell body and proliferative properties, are commonly observed. As reactive astrocytes are involved in the pathogenesis of several brain disorders, the control of astrocytic function has been proposed as a therapeutic strategy, and target molecules to effectively control astrocytic functions have been investigated. The production of brain endothelin-1 (ET-1), which increases in brain disorders, is involved in the pathophysiological response of the nervous system. Endothelin B (ETB) receptors are highly expressed in reactive astrocytes and are upregulated by brain injury. Activation of astrocyte ETB receptors promotes the induction of reactive astrocytes. In addition, the production of various astrocyte-derived factors, including neurotrophic factors and vascular permeability regulators, is regulated by ETB receptors. In animal models of Alzheimer’s disease, brain ischemia, neuropathic pain, and traumatic brain injury, ETB-receptor-mediated regulation of astrocytic activation has been reported to improve brain disorders. Therefore, the astrocytic ETB receptor is expected to be a promising drug target to improve several brain disorders. This article reviews the roles of ETB receptors in astrocytic activation and discusses its possible applications in the treatment of brain disorders.

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Profiles of Executive Function Across Children with Distinct Brain Disorders: Traumatic Brain Injury, Stroke, and Brain Tumor

Journal of the International Neuropsychological Society ◽

10.1017/s1355617717000364 ◽

2017 ◽

Vol 23 (7) ◽

pp. 529-538 ◽

Cited By ~ 8

Author(s):

Gabriel C. Araujo ◽

Tanya N. Antonini ◽

Vicki Anderson ◽

Kathryn A. Vannatta ◽

Christina G. Salley ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Tumor ◽

Executive Function ◽

Brain Injury ◽

Executive Functions ◽

Control Group ◽

Medical Illness ◽

Brain Disorders ◽

Brain Disorder ◽

Orthopedic Injury

AbstractObjectives:This study examined whether children with distinct brain disorders show different profiles of strengths and weaknesses in executive functions, and differ from children without brain disorder.Methods:Participants were children with traumatic brain injury (N=82; 8–13 years of age), arterial ischemic stroke (N=36; 6–16 years of age), and brain tumor (N=74; 9–18 years of age), each with a corresponding matched comparison group consisting of children with orthopedic injury (N=61), asthma (N=15), and classmates without medical illness (N=68), respectively. Shifting, inhibition, and working memory were assessed, respectively, using three Test of Everyday Attention: Children’s Version (TEA-Ch) subtests: Creature Counting, Walk-Don’t-Walk, and Code Transmission. Comparison groups did not differ in TEA-Ch performance and were merged into a single control group. Profile analysis was used to examine group differences in TEA-Ch subtest scaled scores after controlling for maternal education and age.Results:As a whole, children with brain disorder performed more poorly than controls on measures of executive function. Relative to controls, the three brain injury groups showed significantly different profiles of executive functions. Importantly, post hoc tests revealed that performance on TEA-Ch subtests differed among the brain disorder groups.Conclusions:Results suggest that different childhood brain disorders result in distinct patterns of executive function deficits that differ from children without brain disorder. Implications for clinical practice and future research are discussed. (JINS, 2017,23, 529–538)

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Microglia: A Potential Drug Target for Traumatic Axonal Injury

Neural Plasticity ◽

10.1155/2021/5554824 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Xin Huang ◽

Wendong You ◽

Yuanrun Zhu ◽

Kangli Xu ◽

Xiaofeng Yang ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Drug Target ◽

Microglial Activation ◽

Axonal Injury ◽

Traumatic Axonal Injury ◽

Potential Drug Target ◽

Potential Drug ◽

Microglial Phenotype ◽

M2 Phenotype

Traumatic axonal injury (TAI) is a major cause of death and disability among patients with severe traumatic brain injury (TBI); however, no effective therapies have been developed to treat this disorder. Neuroinflammation accompanying microglial activation after TBI is likely to be an important factor in TAI. In this review, we summarize the current research in this field, and recent studies suggest that microglial activation plays an important role in TAI development. We discuss several drugs and therapies that may aid TAI recovery by modulating the microglial phenotype following TBI. Based on the findings of recent studies, we conclude that the promotion of active microglia to the M2 phenotype is a potential drug target for the treatment of TAI.

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