scholarly journals Loss of highwire protects against the deleterious effects of traumatic brain injury in Drosophila Melanogaster

2020 ◽  
Author(s):  
Ciaran Scott Hill ◽  
Andrea Loreto ◽  
Jemeen Sreedha ◽  
David Menon ◽  
Michael Coleman
Keyword(s):  
Traumatic Brain Injury ◽  
Drosophila Melanogaster ◽  
Brain Injury ◽  
Therapeutic Target ◽  
Traumatic Injury ◽  
Underlying Mechanism ◽  
High Impact ◽  
Synaptic Proteins ◽  
Loss Of Function ◽  
Climbing Ability

Abstract BackgroundTraumatic brain injury (TBI) is a major global cause of death and disability. Axonal injury is a major underlying mechanism of TBI and could represent a major therapeutic target. We provide evidence that targeting the axonal death pathway known as Wallerian degeneration (WD) improves outcome in a Drosophila Melanogaster model of high impact trauma. This cell-autonomous neurodegenerative pathway is initiated following axon injury, and in Drosophila, involves activity of the E3 ubiquitin ligase highwire. In this study we explore the effects of that a loss-of-function mutation in the highwire gene has on a range of outcomes following high impact trauma.ResultsResults demonstrate that a loss-of-function mutation in the highwire gene rescues deleterious effects of a traumatic injury, including - improved functional outcomes including climbing ability and flight maintenance, lifespan, survival of a subset of dopaminergic neurons, and retention of synaptic proteins.ConclusionWe demonstrate that a loss-of-function mutation in the highwire gene rescues deleterious effects of a traumatic injury. This data suggests that highwire represents a potential therapeutic target in traumatic injury.

scholarly journals The role of salivary vesicles as a potential inflammatory biomarker to detect traumatic brain injury in mixed martial artists

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rani Matuk ◽  
Mandy Pereira ◽  
Janette Baird ◽  
Mark Dooner ◽  
Yan Cheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Head Injury ◽  
Injury Severity ◽  
Expression Profiles ◽  
High Impact ◽  
Impact Mechanism ◽  
Inflammatory Biomarker ◽  
Potential Biomarker

AbstractTraumatic brain injury (TBI) is of significant concern in the realm of high impact contact sports, including mixed martial arts (MMA). Extracellular vesicles (EVs) travel between the brain and oral cavity and may be isolated from salivary samples as a noninvasive biomarker of TBI. Salivary EVs may highlight acute neurocognitive or neuropathological changes, which may be particularly useful as a biomarker in high impact sports. Pre and post-fight samples of saliva were isolated from 8 MMA fighters and 7 from controls. Real-time PCR of salivary EVs was done using the TaqMan Human Inflammatory array. Gene expression profiles were compared pre-fight to post-fight as well as pre-fight to controls. Largest signals were noted for fighters sustaining a loss by technical knockout (higher impact mechanism of injury) or a full match culminating in referee decision (longer length of fight), while smaller signals were noted for fighters winning by joint or choke submission (lower impact mechanism as well as less time). A correlation was observed between absolute gene information signals and fight related markers of head injury severity. Gene expression was also significantly different in MMA fighters pre-fight compared to controls. Our findings suggest that salivary EVs as a potential biomarker in the acute period following head injury to identify injury severity and can help elucidate pathophysiological processes involved in TBI.

scholarly journals Management of Traumatic Brain Injury: A review Update

2017 ◽  
Vol 6 (2) ◽  
pp. 87-89
Author(s):  
ATM Ashadullah ◽  
Monirul Islam ◽  
Fazley Elahi Milad ◽  
Abdullah Alamgir ◽  
Md Shafiul Alam
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Head Injuries ◽  
Skull Fracture ◽  
Traumatic Injury ◽  
Loss Of Consciousness ◽  
Extradural Haematoma ◽  
Inner Surface ◽  
Injury Patient ◽  
Extradural Haematomas

Traumatic Brain Injury leads to serious consequences. Approximately half of all deaths is related to traumatic injury and the main cause of head trauma. Extradural haematomas (EDH) develops in all major head injuries. A head injury patient who is only temporary loss of consciousness and is left asleep may sometimes be found dead in the bed next morning due to extradural haematoma. Extradural haematoma which lies in between the inner surface of skull and stripes of dural membrane, are nearly always caused by, and located near a skull fracture. The collection takes several forms in terms of size, location, speed of development and effects they exert on patient. Immediate management is necessary to decrease the bad consequences. In this review the management of traumatic brain injury is highlighted.J Shaheed Suhrawardy Med Coll, 2014; 6(2):87-89

scholarly journals Narrative Review of the Pathophysiology of Headaches and Photosensitivity in Mild Traumatic Brain Injury and Concussion

2018 ◽  
Vol 46 (1) ◽  
pp. 14-22 ◽  
Author(s):  
Christopher Mares ◽  
Jehane H. Dagher ◽  
Mona Harissi-Dagher
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Primary Headache ◽  
Underlying Mechanism ◽  
Glutamate Excitotoxicity ◽  
Secondary Headache ◽  
Headache Disorders ◽  
Primary Headache Disorders ◽  
Post Traumatic

AbstractThe most common symptom of post-concussive syndrome (PCS) is post-traumatic headache (PTH) accompanied by photophobia. Post-traumatic headache is currently categorized as a secondary headache disorder with a clinical phenotype described by its main features and resembling one of the primary headache disorders: tension, migraine, migraine-like cluster. Although PTH is often treated with medication used for primary headache disorders, the underlying mechanism for PTH has yet to be elucidated. The goal of this narrative literature review is to determine the current level of knowledge of these PTHs and photophobia in mild traumatic brain injury (mTBI) in order to guide further research and attempt to discover the underlying mechanism to both symptoms. The ultimate purpose is to better understand the pathophysiology of these symptoms in order to provide better and more targeted care to afflicted patients. A review of the literature was conducted using the databases CINAHL, EMBASE, PubMed. All papers were screened for sections on pathophysiology of PTH or photophobia in mTBI patients. Our paper summarizes current hypotheses. Although the exact pathophysiology of PTH and photophobia in mTBI remains to be determined, we highlight several interesting findings and avenues for future research, including central and peripheral explanations for PTH, neuroinflammation, cortical spreading depolarization and the role of glutamate excitotoxicity. We discuss the possible neuroanatomical pathways for photophobia and hypothesize a possible common pathophysiological basis between PTH and photophobia.

scholarly journals Acupuncture Improved Neurological Recovery after Traumatic Brain Injury by Activating BDNF/TrkB Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaohong Li ◽  
Chong Chen ◽  
Xiping Yang ◽  
Jingjing Wang ◽  
Ming-liang Zhao ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Specific Inhibitor ◽  
Underlying Mechanism ◽  
Neurological Impairment ◽  
Neurological Recovery ◽  
Protective Effects ◽  
Neural Repair ◽  
Intractable Problem ◽  
Induced Amelioration

How to promote neural repair following traumatic brain injury (TBI) has long been an intractable problem. Although acupuncture has been demonstrated to facilitate the neurological recovery, the underlying mechanism is elusive. Brain-derived neurotrophic factor (BDNF) exerts substantial protective effects for neurological disorders. In this study, we found that the level of BDNF and tropomyosin receptor kinase B (TrkB) was elevated spontaneously after TBI and reached up to the peak at 12 h. Nevertheless, this enhancement is quickly declined to the normal at 48 h. After combined stimulation at the acupoints of Baihui, Renzhong, Hegu, and Zusanli, we found that BDNF and TrkB were still significantly elevated at 168 h. We also observed that the downstream molecular p-Akt and p-Erk1/2 were significantly increased, suggesting that acupuncture could persistently activate the BDNF/TrkB pathway. To further verify that acupuncture improved recovery through activating BDNF/TrkB pathway, K252a (specific inhibitor of TrkB) was treated by injection stereotaxically into lateral ventricle. We observed that K252a could significantly prevent the acupuncture-induced amelioration of motor, sensation, cognition, and synaptic plasticity. These data indicated that acupuncture promoted the recovery of neurological impairment after TBI by activating BDNF/TrkB signaling pathway, providing new molecular mechanism for understanding traditional therapy of acupuncture.

scholarly journals Changes in TrkB–ERK1/2–CREB/Elk-1 Pathways in Hippocampal Mossy Fiber Organization after Traumatic Brain Injury

2004 ◽  
Vol 24 (8) ◽  
pp. 934-943 ◽  
Author(s):  
Bingren Hu ◽  
Chunli Liu ◽  
Helen Bramlett ◽  
Thomas J. Sick ◽  
Ofelia F. Alonso ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Dentate Gyrus ◽  
Signaling Pathways ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Control Level ◽  
Mossy Fibers ◽  
Underlying Mechanism ◽  
Fiber Organization

Traumatic brain injury (TBI) leads to mossy fiber reorganization, which is considered to be a causative factor in the development of temporal lobe epilepsy. However, the underlying mechanism is not fully understood. Emerging evidence suggests that TrkB–ERK1/2–CREB/Elk-1 pathways are highly related to synaptic plasticity. This study used the rat fluid-percussion injury model to investigate activation of TrkB–ERK1/2–CREB/Elk-1 signaling pathways after TBI. Rats were subjected to 2.0-atm parasagittal TBI followed by 30 minutes, 4 hours, 24 hours, and 72 hours of recovery. After TBI, striking activation of TrkB–ERK1/2–CREB/Elk-1 signaling pathways in mossy fiber organization were observed with confocal microscopy and Western blot analysis. ERK1/2 was highly phosphorylated predominantly in hippocampal mossy fibers, whereas TrkB was phosphorylated both in the mossy fibers and the dentate gyrus region at 30 minutes and 4 hours of recovery after TBI. CREB was also activated at 30 minutes, peaked at 24 hours of recovery, and returned to the control level at 72 hours of recovery in dentate gyrus granule cells. Elk-1 phosphorylation was seen in CA3 neurons at 4 hours after TBI. The results suggest that the signaling pathways of TrkB–ERK1/2–CREB/Elk-1 are highly activated in mossy fiber organization, which may contribute to mossy fiber reorganization seen after TBI.

scholarly journals Neuroprotective effects of crude extract of Crataegus songarica on a rat model of traumatic brain injury

2022 ◽  
Vol 20 (2) ◽  
pp. 293-299
Author(s):  
Xueliang Gao ◽  
Zhao Wang ◽  
Peilei Jia ◽  
Yapeng Zhao ◽  
Kai Wang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Rat Model ◽  
Brain Cortex ◽  
Neuronal Survival ◽  
Underlying Mechanism ◽  
Tunel Staining ◽  
Heme Oxygenase 1 ◽  
Nissl Staining ◽  
Neuroprotective Effects

Purpose: To investigate the protective effect of Crataegus songarica extract (CSCE) against traumatic brain injury (TBI) in rats, and the underlying mechanism of action. Methods: A rat model of TBI was established via tracheal intubation procedure, and the rats were treated with graded doses of CSCE. Neuronal survival was determined by Nissl staining, while neuronal apoptosis was measured using TUNEL-staining. Neurological impairments were determined based on neurological severity score (NSS). Results: Treatment of TBI rats with CSCE enhanced neuronal survival and decreased TUNEL-positive cell fraction in the brain cortex. The treatment prevented elevation of NSS and suppressed mRNA and protein expression levels of IL-6 and TNF-α in brain cortex. Moreover, CSCE treatment prevented TBI-mediated suppression of activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), and attenuated hydrogen peroxide (H2O2) levels in TBI rat brain cortex. Treatment of TBI rats with CSCE down-regulated NF-κB expression, increased Nrf2 expression and up-regulated mRNA expressions of heme oxygenase 1 (HO-1) and quinine oxidoreductase 1 (NQO-1). Conclusion: These results suggest that CSCE prevents TBI-mediated reduction in neuronal survival and inhibits brain cortical neuronal death in rats. It improves NSS and inhibits inflammatory response via activation of Nrf2 pathway and targeting of NF-κB expression. Therefore, CSCE is a potential therapeutic agent for TBI.

scholarly journals A Levee to the Flood: Pre-injury Neuroinflammation and Immune Stress Influence Traumatic Brain Injury Outcome

2022 ◽  
Vol 13 ◽  
Author(s):  
Samuel Houle ◽  
Olga N. Kokiko-Cochran
Keyword(s):  
Risk Factors ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Genetic Risk ◽  
Traumatic Injury ◽  
Genetic Risk Factors ◽  
Post Injury ◽  
Immune Stress ◽  
Age Related

Increasing evidence demonstrates that aging influences the brain's response to traumatic brain injury (TBI), setting the stage for neurodegenerative pathology like Alzheimer's disease (AD). This topic is often dominated by discussions of post-injury aging and inflammation, which can diminish the consideration of those same factors before TBI. In fact, pre-TBI aging and inflammation may be just as critical in mediating outcomes. For example, elderly individuals suffer from the highest rates of TBI of all severities. Additionally, pre-injury immune challenges or stressors may alter pathology and outcome independent of age. The inflammatory response to TBI is malleable and influenced by previous, coincident, and subsequent immune insults. Therefore, pre-existing conditions that elicit or include an inflammatory response could substantially influence the brain's ability to respond to traumatic injury and ultimately affect chronic outcome. The purpose of this review is to detail how age-related cellular and molecular changes, as well as genetic risk variants for AD affect the neuroinflammatory response to TBI. First, we will review the sources and pathology of neuroinflammation following TBI. Then, we will highlight the significance of age-related, endogenous sources of inflammation, including changes in cytokine expression, reactive oxygen species processing, and mitochondrial function. Heightened focus is placed on the mitochondria as an integral link between inflammation and various genetic risk factors for AD. Together, this review will compile current clinical and experimental research to highlight how pre-existing inflammatory changes associated with infection and stress, aging, and genetic risk factors can alter response to TBI.

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