scholarly journals GPR110 ligands reduce chronic optic tract gliosis and visual deficit following repetitive mild traumatic brain injury in mice

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Huazhen Chen ◽  
Karl Kevala ◽  
Elma Aflaki ◽  
Juan Marugan ◽  
Hee-Yong Kim
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Visual Evoked Potential ◽  
Evoked Potential ◽  
Optic Tract ◽  
Primary Microglia ◽  
Visual Dysfunction ◽  
The Brain

Abstract Background Repetitive mild traumatic brain injury (mTBI) can result in chronic visual dysfunction. G-protein receptor 110 (GPR110, ADGRF1) is the target receptor of N-docosahexaenoylethanolamine (synaptamide) mediating the anti-neuroinflammatory function of synaptamide. In this study, we evaluated the effect of an endogenous and a synthetic ligand of GPR110, synaptamide and (4Z,7Z,10Z,13Z,16Z,19Z)-N-(2-hydroxy-2-methylpropyl) docosa-4,7,10,13,16,19-hexaenamide (dimethylsynaptamide, A8), on the mTBI-induced long-term optic tract histopathology and visual dysfunction using Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA), a clinically relevant model of mTBI. Methods The brain injury in wild-type (WT) and GPR110 knockout (KO) mice was induced by CHIMERA applied daily for 3 days, and GPR110 ligands were intraperitoneally injected immediately following each impact. The expression of GPR110 and proinflammatory mediator tumor necrosis factor (TNF) in the brain was measured by using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) in an acute phase. Chronic inflammatory responses in the optic tract and visual dysfunction were assessed by immunostaining for Iba-1 and GFAP and visual evoked potential (VEP), respectively. The effect of GPR110 ligands in vitro was evaluated by the cyclic adenosine monophosphate (cAMP) production in primary microglia isolated from adult WT or KO mouse brains. Results CHIMERA injury acutely upregulated the GPR110 and TNF gene level in mouse brain. Repetitive CHIMERA (rCHIMERA) increased the GFAP and Iba-1 immunostaining of glia cells and silver staining of degenerating axons in the optic tract with significant reduction of N1 amplitude of visual evoked potential at up to 3.5 months after injury. Both GPR110 ligands dose- and GPR110-dependently increased cAMP in cultured primary microglia with A8, a ligand with improved stability, being more effective than synaptamide. Intraperitoneal injection of A8 at 1 mg/kg or synaptamide at 5 mg/kg significantly reduced the acute expression of TNF mRNA in the brain and ameliorated chronic optic tract microgliosis, astrogliosis, and axonal degeneration as well as visual deficit caused by injury in WT but not in GPR110 KO mice. Conclusion Our data demonstrate that ligand-induced activation of the GPR110/cAMP system upregulated after injury ameliorates the long-term optic tract histopathology and visual impairment caused by rCHIMERA. Based on the anti-inflammatory nature of GPR110 activation, we suggest that GPR110 ligands may have therapeutic potential for chronic visual dysfunction associated with mTBI.

Practical Challenges in Collecting Head Impact Biomechanics Data in Real-World Scenarios via a Helmet-Based Accelerometer System

2013 ◽  
Author(s):  
Mari A. Allison ◽  
Yun Seok Kang ◽  
Matthew R. Maltese ◽  
John H. Bolte ◽  
Kristy B. Arbogast
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Real World ◽  
Head Impact ◽  
Permanent Damage ◽  
Head Impact Biomechanics ◽  
Impact Biomechanics ◽  
The Brain

Recent studies have shown that mild traumatic brain injury (mTBI) can have long-term neurological consequences and may cause permanent damage to the brain [1,2]. Given estimates that millions of these injuries occur each year [3], this knowledge has created a demand for countermeasures to prevent mTBI. In order to create countermeasures, the biomechanical inputs leading to mTBI, which are still a matter of debate, must be better understood in both children and adults.

scholarly journals Repetitive Traumatic Brain Injury Is Associated With TDP-43 Alterations, Neurodegeneration, and Glial Activation in Mice

2020 ◽  
Vol 80 (1) ◽  
pp. 2-14
Author(s):  
Jelena Rajič Bumber ◽  
Kristina Pilipović ◽  
Tamara Janković ◽  
Petra Dolenec ◽  
Nika Gržeta ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Stress Response ◽  
Frontal Cortex ◽  
Mild Traumatic Brain Injury ◽  
Optic Tract ◽  
Dna Binding Protein ◽  
Glial Activation ◽  
Transient Stress ◽  
The Brain

Abstract Increasing evidence points to a relationship between repetitive mild traumatic brain injury (mTBI), the Tar DNA binding protein 43 (TDP-43) pathology and some neurodegenerative diseases, but the underlying pathophysiological mechanisms are still unknown. We examined TDP-43 regulation, neurodegeneration, and glial responses following repetitive mTBI in nontransgenic mice and in animals with overexpression of human mutant TDP-43 protein (TDP-43G348C). In the frontal cortices of the injured nontransgenic animals, early TDP-43 cytoplasmatic translocation and overexpression of the protein and its pathological forms were detected. In the injured animals of both genotypes, neurodegeneration and pronounced glial activity were detected in the optic tract. In TDP-43G348C mice, these changes were significantly higher at day 7 after the last mTBI compared with the values in the nontransgenic animals. Results of this study suggest that the changes in the TDP-43 regulation in the frontal cortices of the nontransgenic animals were a transient stress response to the brain injury. Repetitive mTBI did not produce additional TDP-43 dysregulation or neurodegeneration or pronounced gliosis in the frontal cortex of TDP-43G348C mice. Our research also suggests that overexpression of mutated human TDP-43 possibly predisposes the brain to more intense neurodegeneration and glial activation in the optic tract after repetitive mTBI.

VEP and Human Attention: Translation from Laboratory to Clinic

2015 ◽  
pp. 14-29
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Visual Evoked Potential ◽  
Evoked Potential ◽  
Alpha Band ◽  
Attentional Deficit ◽  
Human Attention ◽  
Vision Rehabilitation ◽  
Visual Evoked

The purpose is to review recent studies from our laboratory that used the visual-evoked potential (VEP) to assess attention in both the visually-normal (VN) and mild traumatic brain injury (mTBI) populations. The VEP (amplitude and latency), and attention-related alpha band responses, were assessed. The alpha responses were abnormal in those with mTBI. Furthermore, these values differentiated well between mTBI with versus without an attentional deficit. Following oculomotor vision rehabilitation, the alpha and VEP responses increased significantly. The VEP technique can be used reliably in both clinic and laboratory settings to detect attention objectively in both VN and mTBI populations.

Providing Care of Mild Traumatic Brain Injury by the Family Practice/Primary Care Optometrist

2018 ◽  
pp. 110-119
Keyword(s):  
Primary Care ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Family Practice ◽  
Advanced Training ◽  
Entry Level ◽  
The Family ◽  
Basic Understanding ◽  
The Brain

Primary Objectives: By extending the scope of knowledge of the primary care optometrist, the brain injury population will have expanded access to entry level neurooptometric care by optometric providers who have a basic understanding of their neurovisual problems, be able to provide some treatment and know when to refer to their colleagues who have advanced training in neuro-optometric rehabilitation.

scholarly journals What are the strongest indicators of intracerebral hemorrhage in mild traumatic brain injury?

2021 ◽  
Vol 6 (1) ◽  
pp. e000717
Author(s):  
Panu Teeratakulpisarn ◽  
Phati Angkasith ◽  
Thanakorn Wannakul ◽  
Parichat Tanmit ◽  
Supatcha Prasertcharoensuk ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
High Risk ◽  
Ct Scan ◽  
Mild Traumatic Brain Injury ◽  
Skull Fracture ◽  
Brain Ct ◽  
Baseline Characteristics ◽  
Gcs Score ◽  
The Brain

BackgroundAlthough there are eight factors known to indicate a high risk of intracranial hemorrhage (ICH) in mild traumatic brain injury (TBI), identification of the strongest of these factors may optimize the utility of brain CT in clinical practice. This study aimed to evaluate the predictors of ICH based on baseline characteristics/mode of injury, indications for brain CT, and a combination of both to determine the strongest indicator.MethodsThis was a descriptive, retrospective, analytical study. The inclusion criteria were diagnosis of mild TBI, high risk of ICH, and having undergone a CT scan of the brain. The outcome of the study was any type of ICH. Stepwise logistic regression analysis was used to find the strongest predictors according to three models: (1) injury pattern and baseline characteristics, (2) indications for CT scan of the brain, and (3) a combination of models 1 and 2.ResultsThere were 100 patients determined to be at risk of ICH based on indications for CT of the brain in patients with acute head injury. Of these, 24 (24.00%) had ICH. Model 1 found that injury due to motor vehicle crash was a significant predictor of ICH, with an adjusted OR (95% CI) of 11.53 (3.05 to 43.58). Models 2 and 3 showed Glasgow Coma Scale (GCS) score of 13 to 14 after 2 hours of observation and open skull or base of skull fracture to be independent predictors, with adjusted OR (95% CI) of 11.77 (1.32 to 104.96) and 5.88 (1.08 to 31.99) according to model 2.DiscussionOpen skull or base of skull fracture and GCS score of 13 to 14 after 2 hours of observation were the two strongest predictors of ICH in mild TBI.Level of evidenceIII.

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