In vivo expression of neuroglobin in reactive astrocytes during neuropathology in murine models of traumatic brain injury, cerebral malaria, and autoimmune encephalitis

Glia ◽  
2010 ◽  
Vol 58 (10) ◽  
pp. 1220-1227 ◽  
Author(s):  
Brian DellaValle ◽  
Casper Hempel ◽  
Jørgen A. L. Kurtzhals ◽  
Milena Penkowa
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cerebral Malaria ◽  
Autoimmune Encephalitis ◽  
Reactive Astrocytes ◽  
Murine Models ◽  
In Vivo Expression

scholarly journals PD-L1-expressing astrocytes act as a gate-keeper for neuroinflammation in the central nervous system of mice with traumatic brain injury

2021 ◽  
Author(s):  
Xiang Gao ◽  
Wei Li ◽  
Fahim Syed ◽  
Fang Yuan ◽  
Ping Li ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
De Novo ◽  
Gene Knockout ◽  
Reactive Astrocytes ◽  
Immune Checkpoints ◽  
Enhanced Production ◽  
The Brain

Background: Tissue damage and cellular destruction are the major events in traumatic brain injury (TBI), which trigger sterile neuroimmune and neuroinflammatory responses in the brain. While appropriate acute and transient neuroimmune and neuroinflammatory responses facilitate the repair and adaptation of injured brain tissues, prolonged and excessive neuroimmune and neuroinflammatory responses exacerbate brain damage. The mechanisms that control the intensity and duration of neuroimmune and neuroinflammatory responses in TBI largely remain elusive. Methods: We used the controlled cortical impact (CCI) model of TBI to study the role of immune checkpoints (ICPs), key regulators of immune homeostasis, in the regulation of neuroimmune and neuroinflammatory responses in the brain in vivo. Results: We found that de novo expression of PD-L1, a potent inhibitory ICP, was robustly and transiently induced in reactive astrocytes, but not in microglial cells, neurons, or oligodendrocyte progenitor cells (OPCs). These PD-L1+ reactive astrocytes were highly enriched to form a dense zone around the TBI lesion. Blockade of PD-L1 signaling enlarged brain tissue cavity size, increased infiltration of inflammatory Ly-6CHigh monocytes/macrophages (M/Mɸ) but not tissue-repairing Ly-6CLow/F4/80+ M/Mɸ, and worsened TBI outcomes in mice. PD-L1 gene knockout enhanced production of CCL2 that interacted with its cognate receptor CCR2 on Ly-6CHigh M/Mϕ to chemotactically recruit these cells into inflammatory sites. Mechanically, PD-L1 signaling in astrocytes likely exhibits dual inhibitory activities for the prevention of excessive neuroimmune and neuroinflammatory responses to TBI through (1) the PD-1/PD-L1 axis to suppress the activity of brain-infiltrating PD-1+ immune cells such as PD-1+ T cells, and (2) PD-L1 reverse signaling to regulate the timing and intensity of astrocyte reactions to TBI. Conclusions: PD-L1+ astrocytes act as a gatekeeper to the brain to control TBI-related neuroimmune and neuroinflammatory responses, thereby opening a novel avenue to study the role of ICP-neuroimmune axes in the pathophysiology of TBI and other neurological disorders.

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

2021 ◽  
Vol 22 (9) ◽  
pp. 4333
Author(s):  
Yutaka Koyama
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neurotrophic Factors ◽  
Drug Target ◽  
Therapeutic Strategy ◽  
Reactive Astrocytes ◽  
Brain Disorders ◽  
Etb Receptor ◽  
Target Molecules ◽  
Endothelin B

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.

An Activatable NIR‐II Nanoprobe for In Vivo Early Real‐Time Diagnosis of Traumatic Brain Injury

2019 ◽  
Vol 59 (1) ◽  
pp. 247-252 ◽  
Author(s):  
Chunyan Li ◽  
Wanfei Li ◽  
Huanhuan Liu ◽  
Yejun Zhang ◽  
Guangcun Chen ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Real Time ◽  
Time Diagnosis

scholarly journals Using the Olfactory System as an In Vivo Model To Study Traumatic Brain Injury and Repair

2014 ◽  
Vol 31 (14) ◽  
pp. 1277-1291 ◽  
Author(s):  
Elizabeth Steuer ◽  
Michele L. Schaefer ◽  
Leonardo Belluscio
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Olfactory System ◽  
In Vivo Model ◽  
Injury And Repair

scholarly journals In vivo imaging of rapid deformation and strain in an animal model of traumatic brain injury

2006 ◽  
Vol 39 (6) ◽  
pp. 1086-1095 ◽  
Author(s):  
Philip V. Bayly ◽  
Erin E. Black ◽  
Rachel C. Pedersen ◽  
Elizabeth P. Leister ◽  
Guy M. Genin
Keyword(s):  
Traumatic Brain Injury ◽  
Animal Model ◽  
Brain Injury ◽  
In Vivo Imaging ◽  
Rapid Deformation

scholarly journals Traumatic brain injury to primary visual cortex produces long-lasting circuit dysfunction

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jan C. Frankowski ◽  
Andrzej T. Foik ◽  
Alexa Tierno ◽  
Jiana R. Machhor ◽  
David C. Lyon ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Visual Cortex ◽  
Brain Injury ◽  
Primary Visual Cortex ◽  
Visual Stimuli ◽  
Orientation Tuning ◽  
V1 Neurons ◽  
Adult Mice ◽  
Electrophysiological Recordings

AbstractPrimary sensory areas of the mammalian neocortex have a remarkable degree of plasticity, allowing neural circuits to adapt to dynamic environments. However, little is known about the effects of traumatic brain injury on visual circuit function. Here we used anatomy and in vivo electrophysiological recordings in adult mice to quantify neuron responses to visual stimuli two weeks and three months after mild controlled cortical impact injury to primary visual cortex (V1). We found that, although V1 remained largely intact in brain-injured mice, there was ~35% reduction in the number of neurons that affected inhibitory cells more broadly than excitatory neurons. V1 neurons showed dramatically reduced activity, impaired responses to visual stimuli and weaker size selectivity and orientation tuning in vivo. Our results show a single, mild contusion injury produces profound and long-lasting impairments in the way V1 neurons encode visual input. These findings provide initial insight into cortical circuit dysfunction following central visual system neurotrauma.

scholarly journals Traumatic Brain Injury as a Disorder of Brain Connectivity

2016 ◽  
Vol 22 (2) ◽  
pp. 120-137 ◽  
Author(s):  
Jasmeet P. Hayes ◽  
Erin D. Bigler ◽  
Mieke Verfaellie
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Functional Connectivity ◽  
Negative Impact ◽  
Axonal Injury ◽  
Resting State Functional Connectivity ◽  
Post Injury ◽  
Recent Advances

AbstractObjectives:Recent advances in neuroimaging methodologies sensitive to axonal injury have made it possible to assess in vivo the extent of traumatic brain injury (TBI) -related disruption in neural structures and their connections. The objective of this paper is to review studies examining connectivity in TBI with an emphasis on structural and functional MRI methods that have proven to be valuable in uncovering neural abnormalities associated with this condition.Methods:We review studies that have examined white matter integrity in TBI of varying etiology and levels of severity, and consider how findings at different times post-injury may inform underlying mechanisms of post-injury progression and recovery. Moreover, in light of recent advances in neuroimaging methods to study the functional connectivity among brain regions that form integrated networks, we review TBI studies that use resting-state functional connectivity MRI methodology to examine neural networks disrupted by putative axonal injury.Results:The findings suggest that TBI is associated with altered structural and functional connectivity, characterized by decreased integrity of white matter pathways and imbalance and inefficiency of functional networks. These structural and functional alterations are often associated with neurocognitive dysfunction and poor functional outcomes.Conclusions:TBI has a negative impact on distributed brain networks that lead to behavioral disturbance. (JINS, 2016,22, 120–137)

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