Traumatic Brain Injury: Mechanisms of Glial Response

Mira, Rodrigo G.; Lira, Matías; Cerpa, Waldo

doi:10.3389/fphys.2021.740939

Cited by 112 publications

(94 citation statements)

References 179 publications

(204 reference statements)

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“…Common causes of TBI are violent hits to the head or objects penetrating through the skull and into the brain. The pathophysiology of TBI is complex [85], involving neuroinflammation [86,87], oxidative stress [88], mitochondrial dysfunction [89,90], demyelination, and other mechanisms [91]. Excitotoxicity is at the core of neural loss in response to TBI.…”

Section: Naag In Traumatic Brain Injurymentioning

confidence: 99%

N-Acetyl-Aspartyl-Glutamate in Brain Health and Disease

Morland

Nordengen

2022

IJMS

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N-acetyl-aspartyl-glutamate (NAAG) is the most abundant dipeptide in the brain, where it acts as a neuromodulator of glutamatergic synapses by activating presynaptic metabotropic glutamate receptor 3 (mGluR3). Recent data suggest that NAAG is selectively localized to postsynaptic dendrites in glutamatergic synapses and that it works as a retrograde neurotransmitter. NAAG is released in response to glutamate and provides the postsynaptic neuron with a feedback mechanisms to inhibit excessive glutamate signaling. A key regulator of synaptically available NAAG is rapid degradation by the extracellular enzyme glutamate carboxypeptidase II (GCPII). Increasing endogenous NAAG—for instance by inhibiting GCPII—is a promising treatment option for many brain disorders where glutamatergic excitotoxicity plays a role. The main effect of NAAG occurs through increased mGluR3 activation and thereby reduced glutamate release. In the present review, we summarize the transmitter role of NAAG and discuss the involvement of NAAG in normal brain physiology. We further present the suggested roles of NAAG in various neurological and psychiatric diseases and discuss the therapeutic potential of strategies aiming to enhance NAAG levels.

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Section: Naag In Traumatic Brain Injurymentioning

confidence: 99%

N-Acetyl-Aspartyl-Glutamate in Brain Health and Disease

Morland

Nordengen

2022

IJMS

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“…Astrocytes and microglia link with each other through the cytokines and other extracellular mediators they release [ 97 , 98 ]. They play critical roles in the brain’s ion and water homeostasis, energy metabolism, blood–brain barrier, and immune response, and they change their morphology and protein expression, releasing both pro- and anti-inflammatory mediators [ 99 ]. In the present study, our results elucidated that lupeol reduced the number of activated astrocytes and microglia in the adult mouse cortex and hippocampus regions.…”

Section: Discussionmentioning

confidence: 99%

Lupeol Treatment Attenuates Activation of Glial Cells and Oxidative-Stress-Mediated Neuropathology in Mouse Model of Traumatic Brain Injury

Ahmad

Khan

Rehman

et al. 2022

IJMS

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Traumatic brain injury (TBI) signifies a major cause of death and disability. TBI causes central nervous system (CNS) damage under a variety of mechanisms, including protein aggregation, mitochondrial dysfunction, oxidative stress, and neuroinflammation. Astrocytes and microglia, cells of the CNS, are considered the key players in initiating an inflammatory response after injury. Several evidence suggests that activation of astrocytes/microglia and ROS/LPO have the potential to cause more harmful effects in the pathological processes following traumatic brain injury (TBI). Previous studies have established that lupeol provides neuroprotection through modulation of inflammation, oxidative stress, and apoptosis in Aβ and LPS model and neurodegenerative disease. However, the effects of lupeol on apoptosis caused by inflammation and oxidative stress in TBI have not yet been investigated. Therefore, we explored the role of Lupeol on antiapoptosis, anti-inflammatory, and antioxidative stress and its potential mechanism following TBI. In these experiments, adult male mice were randomly divided into four groups: control, TBI, TBI+ Lupeol, and Sham group. Western blotting, immunofluorescence staining, and ROS/LPO assays were performed to investigate the role of lupeol against neuroinflammation, oxidative stress, and apoptosis. Lupeol treatment reversed TBI-induced behavioral and memory disturbances. Lupeol attenuated TBI-induced generation of reactive oxygen species/lipid per oxidation (ROS/LPO) and improved the antioxidant protein level, such as nuclear factor erythroid 2-related factor 2 (Nrf2) and heme-oxygenase 1 (HO-1) in the mouse brain. Similarly, our results indicated that lupeol treatment inhibited glial cell activation, p-NF-κB, and downstream signaling molecules, such as TNF-α, COX-2, and IL-1β, in the mouse cortex and hippocampus. Moreover, lupeol treatment also inhibited mitochondrial apoptotic signaling molecules, such as caspase-3, Bax, cytochrome-C, and reversed deregulated Bcl2 in TBI-treated mice. Overall, our study demonstrated that lupeol inhibits the activation of astrocytes/microglia and ROS/LPO that lead to oxidative stress, neuroinflammation, and apoptosis followed by TBI.

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“…As the first responders to TBI, microglia will be activated rapidly and change their morphology to form larger cell bodies with ramified cellular structures ( 65 ). After activation, microglia can proliferate and migrate to the injury location and polarize and induce the release of cytokines ( 66 ).…”

Section: Microglia Activationmentioning

confidence: 99%

“…The intercellular crosstalk between astrocytes and microglia has contributed an essential role to the neuroinflammation following TBI ( 65 ). To date, several signal pathways were found to participate in the crosstalk between the microglia and the astrocytes, oligodendrocyte, neurons, and NG2 cells ( Figure 1 ).…”

Section: Glial Interactionmentioning

confidence: 99%

Neuroinflammation Following Traumatic Brain Injury: Take It Seriously or Not

Zheng

Lee

et al. 2022

Front. Immunol.

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Traumatic brain injury (TBI) is associated with high mortality and disability, with a substantial socioeconomic burden. With the standardization of the treatment process, there is increasing interest in the role that the secondary insult of TBI plays in outcome heterogeneity. The secondary insult is neither detrimental nor beneficial in an absolute sense, among which the inflammatory response was a complex cascade of events and can thus be regarded as a double-edged sword. Therefore, clinicians should take the generation and balance of neuroinflammation following TBI seriously. In this review, we summarize the current human and animal model studies of neuroinflammation and provide a better understanding of the inflammatory response in the different stages of TBI. In particular, advances in neuroinflammation using proteomic and transcriptomic techniques have enabled us to identify a functional specific delineation of the immune cell in TBI patients. Based on recent advances in our understanding of immune cell activation, we present the difference between diffuse axonal injury and focal brain injury. In addition, we give a figurative profiling of the general paradigm in the pre- and post-injury inflammatory settings employing a bow-tie framework.

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Traumatic Brain Injury: Mechanisms of Glial Response

Cited by 112 publications

References 179 publications

N-Acetyl-Aspartyl-Glutamate in Brain Health and Disease

N-Acetyl-Aspartyl-Glutamate in Brain Health and Disease

Lupeol Treatment Attenuates Activation of Glial Cells and Oxidative-Stress-Mediated Neuropathology in Mouse Model of Traumatic Brain Injury

Neuroinflammation Following Traumatic Brain Injury: Take It Seriously or Not

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