The p38  MAPK Regulates Microglial Responsiveness to Diffuse Traumatic Brain Injury

Traumatic brain injury (TBI) is characterized by physical damage to the brain tissues, ensuing transitory or permanent neurological dysfunction featured with neuronal loss and subsequent brain damage. Sevoflurane, a widely used halogenated anesthetic in clinical settings, has been reported to alleviate neuron apoptosis in TBI. Nevertheless, the underlying mechanism behind this alleviation remains unknown, and thus was the focus of the current study. First, Feeney models were established to induce TBI in rats. Subsequently, evaluation of the modified neurological severity scores, measurement of brain water content, Nissl staining, and TUNEL assay were employed to investigate the neuroprotective effects of sevoflurane. Immunofluorescence and Western blot analysis were further applied to detect the expression patterns of apoptosis-related proteins as well as the activation of the p38-mitogen-activated protein kinase (MAPK) signaling pathway within the lesioned cortex. Additionally, a stretch injury model comprising cultured neurons was established, followed by neuron-specific enolase staining and Sholl analysis. Mechanistic analyses were performed using dual-luciferase reporter gene and chromatin immunoprecipitation assays. The results demonstrated sevoflurane treatment brought about a decrease blood-brain barrier (BBB) permeability, brain water content, brain injury and neuron apoptosis, to improve neurological function. The neuroprotective action of sevoflurane could be attenuated by inactivation of the p38-MAPK signaling pathway. Mechanistically, sevoflurane exerted an inhibitory effect on neuron apoptosis by up-regulating enhancer of zeste homolog 2 (EZH2), which targeted Krüppel-like factor 4 (KLF4) and inhibited KLF4 transcription. Collectively, our findings indicate that sevoflurane suppresses neuron apoptosis induced by TBI through activation of the p38-MAPK signaling pathway via the EZH2/KLF4 axis, providing a novel mechanistic explanation for neuroprotection of sevoflurane in TBI.

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Neuroprotective effect of berberine agonist against impairment of learning and memory skills in severe traumatic brain injury via Sirt1/p38 MAPK expression

Molecular Medicine Reports ◽

10.3892/mmr.2018.8674 ◽

2018 ◽

Cited By ~ 2

Author(s):

Jianping Wang ◽

Yamin Zhang

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Learning And Memory ◽

P38 Mapk ◽

Severe Traumatic Brain Injury ◽

Neuroprotective Effect

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Disrupting nNOS–PSD95 Interaction Improves Neurological and Cognitive Recoveries after Traumatic Brain Injury

Cerebral Cortex ◽

10.1093/cercor/bhaa002 ◽

2020 ◽

Vol 30 (7) ◽

pp. 3859-3871 ◽

Cited By ~ 3

Author(s):

Wenrui Qu ◽

Nai-Kui Liu ◽

Xiangbing Wu ◽

Ying Wang ◽

Yongzhi Xia ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

P38 Mapk ◽

Brain Lesion ◽

Mapk Signaling ◽

Motor Deficits ◽

Neuronal Cultures ◽

Normal Brain ◽

Lesion Volume ◽

Oxide Synthase

Abstract Excessive activation of N-methyl-D-aspartate receptors (NMDARs) and the resulting neuronal nitric oxide synthase (nNOS) activation plays a crucial role in the pathogenesis of traumatic brain injury (TBI). However, directly inhibiting NMDARs or nNOS produces adverse side effects because they play key physiological roles in the normal brain. Since interaction of nNOS–PSD95 is a key step in NMDAR-mediated excitotoxicity, we investigated whether disrupting nNOS–PSD95 interaction with ZL006, an inhibitor of nNOS–PSD95 interaction, attenuates NMDAR-mediated excitotoxicity. In cortical neuronal cultures, ZL006 treatment significantly reduced glutamate-induced neuronal death. In a mouse model of controlled cortical impact (CCI), administration of ZL006 (10 mg/kg, i.p.) at 30 min postinjury significantly inhibited nNOS–PSD95 interaction, reduced TUNEL- and phospho-p38-positive neurons in the motor cortex. ZL006 treatment also significantly reduced CCI-induced cortical expression of apoptotic markers active caspase-3, PARP-1, ratio of Bcl-2/Bax, and phosphorylated p38 MAPK (p-p38). Functionally, ZL006 treatment significantly improved neuroscores and sensorimotor performance, reduced somatosensory and motor deficits, reversed CCI-induced memory deficits, and attenuated cognitive impairment. Histologically, ZL006 treatment significantly reduced the brain lesion volume. These findings collectively suggest that blocking nNOS–PSD95 interaction represents an attractive strategy for ameliorating consequences of TBI and that its action is mediated via inhibiting neuronal apoptosis and p38 MAPK signaling.

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Hyperbaric oxygen therapy improves neurological function via the p38-MAPK/CCL2 signaling pathway following traumatic brain injury

Neuroreport ◽

10.1097/wnr.0000000000001719 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Yingzi Jiang ◽

Yuwen Chen ◽

Chunling Huang ◽

Anqi Xia ◽

Guohua Wang ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Signaling Pathway ◽

P38 Mapk ◽

Hyperbaric Oxygen ◽

Hyperbaric Oxygen Therapy ◽

Oxygen Therapy ◽

Neurological Function

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SIRT1 plays a neuroprotective role in traumatic brain injury in rats via inhibiting the p38 MAPK pathway

Acta Pharmacologica Sinica ◽

10.1038/aps.2016.130 ◽

2016 ◽

Vol 38 (2) ◽

pp. 168-181 ◽

Cited By ~ 29

Author(s):

Hong Yang ◽

Zheng-tao Gu ◽

Li Li ◽

Mac Maegele ◽

Bi-ying Zhou ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

P38 Mapk ◽

Mapk Pathway ◽

P38 Mapk Pathway

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Cognitive control constrains memory attributions

Behavioral and Brain Sciences ◽

10.1017/s0140525x19001869 ◽

2019 ◽

Vol 42 ◽

Author(s):

Colleen M. Kelley ◽

Larry L. Jacoby

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Cognitive Control

Abstract Cognitive control constrains retrieval processing and so restricts what comes to mind as input to the attribution system. We review evidence that older adults, patients with Alzheimer's disease, and people with traumatic brain injury exert less cognitive control during retrieval, and so are susceptible to memory misattributions in the form of dramatic levels of false remembering.

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Lessons Learned From Coaching Postsecondary Students With Traumatic Brain Injury

Perspectives of the ASHA Special Interest Groups ◽

10.1044/2019_persp-19-00092 ◽

2020 ◽

Vol 5 (1) ◽

pp. 88-96

Author(s):

Mary R. T. Kennedy

Keyword(s):

College Students ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Sense Of Self ◽

Scientific Evidence ◽

Sudden Onset ◽

Lessons Learned ◽

Speech Language Pathologists ◽

The Brain ◽

Exhaustive List

Purpose The purpose of this clinical focus article is to provide speech-language pathologists with a brief update of the evidence that provides possible explanations for our experiences while coaching college students with traumatic brain injury (TBI). Method The narrative text provides readers with lessons we learned as speech-language pathologists functioning as cognitive coaches to college students with TBI. This is not meant to be an exhaustive list, but rather to consider the recent scientific evidence that will help our understanding of how best to coach these college students. Conclusion Four lessons are described. Lesson 1 focuses on the value of self-reported responses to surveys, questionnaires, and interviews. Lesson 2 addresses the use of immediate/proximal goals as leverage for students to update their sense of self and how their abilities and disabilities may alter their more distal goals. Lesson 3 reminds us that teamwork is necessary to address the complex issues facing these students, which include their developmental stage, the sudden onset of trauma to the brain, and having to navigate going to college with a TBI. Lesson 4 focuses on the need for college students with TBI to learn how to self-advocate with instructors, family, and peers.

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