Visual Dysfunction after Repetitive Mild Traumatic Brain Injury in a Mouse Model and Ramifications on Behavioral Metrics

2021 ◽  
Author(s):  
Nicholas Morriss ◽  
Grace Conley ◽  
Nathaniel Hodgson ◽  
Masen Boucher ◽  
Sara Ospina-Mora ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mouse Model ◽  
Mild Traumatic Brain Injury ◽  
Visual Dysfunction

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.

Chronic cerebrovascular abnormalities in a mouse model of repetitive mild traumatic brain injury

Brain Injury ◽  
2016 ◽  
Vol 30 (12) ◽  
pp. 1414-1427 ◽  
Author(s):  
Cillian E. Lynch ◽  
Gogce Crynen ◽  
Scott Ferguson ◽  
Benoit Mouzon ◽  
Daniel Paris ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mouse Model ◽  
Mild Traumatic Brain Injury

A novel repetitive mild traumatic brain injury mouse model for chronic traumatic encephalopathy research

2018 ◽  
Vol 308 ◽  
pp. 162-172 ◽  
Author(s):  
Xintong Ge ◽  
Jinwen Yu ◽  
Shan Huang ◽  
Zhenyu Yin ◽  
Zhaoli Han ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mouse Model ◽  
Mild Traumatic Brain Injury ◽  
Chronic Traumatic Encephalopathy

scholarly journals Long-Term Cognitive Impairments and Pathological Alterations in a Mouse Model of Repetitive Mild Traumatic Brain Injury

2014 ◽  
Vol 5 ◽  
Author(s):  
Jian Luo ◽  
Andy Nguyen ◽  
Saul Villeda ◽  
Hui Zhang ◽  
Zhaoqing Ding ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mouse Model ◽  
Mild Traumatic Brain Injury ◽  
Cognitive Impairments

Anxiolytic- and antidepressant-like effects of Silymarin compared to diazepam and fluoxetine in a mouse model of mild traumatic brain injury

2018 ◽  
Vol 338 ◽  
pp. 159-173 ◽  
Author(s):  
Morteza Kosari-Nasab ◽  
Ghaffar Shokouhi ◽  
Amir Ghorbanihaghjo ◽  
Mehran Mesgari Abbasi ◽  
Ali-Akbar Salari
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mouse Model ◽  
Mild Traumatic Brain Injury

scholarly journals Oral Cannabidiol Prevents Allodynia and Neurological Dysfunctions in a Mouse Model of Mild Traumatic Brain Injury

2019 ◽  
Vol 10 ◽  
Author(s):  
Carmela Belardo ◽  
Monica Iannotta ◽  
Serena Boccella ◽  
Rosamaria Cristina Rubino ◽  
Flavia Ricciardi ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mouse Model ◽  
Mild Traumatic Brain Injury

scholarly journals Conditioned Contextual Freezing is A Neurobehavioral Biomarker of Axonal Injury Indicated by Reduced Fractional Anisotropy in A Mouse Model of Blast-Induced Mild Traumatic Brain Injury

Shock ◽  
2019 ◽  
Vol 53 (6) ◽  
pp. 744-753 ◽  
Author(s):  
Craig Weiss ◽  
Frances R. Lendacki ◽  
Paul H. Rigby ◽  
Alice M. Wyrwicz ◽  
John F. Disterhoft ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mouse Model ◽  
Fractional Anisotropy ◽  
Mild Traumatic Brain Injury ◽  
Axonal Injury

Protective Effects of N-Oleoylglycine in a Mouse Model of Mild Traumatic Brain Injury

2020 ◽  
Vol 11 (8) ◽  
pp. 1117-1128
Author(s):  
Fabiana Piscitelli ◽  
Francesca Guida ◽  
Livio Luongo ◽  
Fabio Arturo Iannotti ◽  
Serena Boccella ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mouse Model ◽  
Mild Traumatic Brain Injury ◽  
Protective Effects
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