scholarly journals Early cerebrovascular and long-term neurological modifications ensue following juvenile mild traumatic brain injury in male mice

2020 ◽  
Vol 141 ◽  
pp. 104952 ◽  
Author(s):  
Aleksandra Ichkova ◽  
Beatriz Rodriguez-Grande ◽  
Emma Zub ◽  
Amel Saudi ◽  
Marie-Line Fournier ◽  
...  
2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Huazhen Chen ◽  
Karl Kevala ◽  
Elma Aflaki ◽  
Juan Marugan ◽  
Hee-Yong Kim

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.


2014 ◽  
Vol 219 (4) ◽  
pp. e144-e145
Author(s):  
Elizabeth Shinn ◽  
Amy Pate ◽  
Frederique Pinto ◽  
Akella Chendrasekhar

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 36
Author(s):  
Rany Vorn ◽  
Maiko Suarez ◽  
Jacob C. White ◽  
Carina A. Martin ◽  
Hyung-Suk Kim ◽  
...  

Chronic mild traumatic brain injury (mTBI) has long-term consequences, such as neurological disability, but its pathophysiological mechanism is unknown. Exosomal microRNAs (exomiRNAs) may be important mediators of molecular and cellular changes involved in persistent symptoms after mTBI. We profiled exosomal microRNAs (exomiRNAs) in plasma from young adults with or without a chronic mTBI to decipher the underlying mechanisms of its long-lasting symptoms after mTBI. We identified 25 significantly dysregulated exomiRNAs in the chronic mTBI group (n = 29, with 4.48 mean years since the last injury) compared to controls (n = 11). These miRNAs are associated with pathways of neurological disease, organismal injury and abnormalities, and psychological disease. Dysregulation of these plasma exomiRNAs in chronic mTBI may indicate that neuronal inflammation can last long after the injury and result in enduring and persistent post-injury symptoms. These findings are useful for diagnosing and treating chronic mTBIs.


2021 ◽  
Vol 268 (11) ◽  
pp. 4404-4405
Author(s):  
Daan P. J. Verberne ◽  
Rudolf W. H. M. Ponds ◽  
Mariëlle E. A. L. Kroese ◽  
Melloney L. M. Wijenberg ◽  
Dennis G. Barten ◽  
...  

Radiology ◽  
2016 ◽  
Vol 280 (1) ◽  
pp. 212-219 ◽  
Author(s):  
Jeffrey B. Ware ◽  
Rosette C. Biester ◽  
Elizabeth Whipple ◽  
Keith M. Robinson ◽  
Richard J. Ross ◽  
...  

Author(s):  
Mark Wilson

Interest in concussion and sports-related injury has intensified in recent years for three main reasons: (1) it is a preventable form of brain injury; (2) there is increasing evidence that repeated injury can result in long-term neurocognitive loss; and (3) as a result there are potential medicolegal costs to organizations that, possibly inadvertently, allow this form of brain injury to occur within their sport. The long-term effects of boxing resulting in dementia pugilistica have been appreciated for some time, however the results of repeated mild head injury in other sports is now under focus. Concussion, increasingly termed mild traumatic brain injury, should be graded. Imaging, removal from, and return to sport are all discussed in this chapter.


Brain Injury ◽  
2020 ◽  
Vol 34 (4) ◽  
pp. 556-566 ◽  
Author(s):  
Erica Sercy ◽  
Alessandro Orlando ◽  
Matthew Carrick ◽  
Mark Lieser ◽  
Robert Madayag ◽  
...  

2020 ◽  
Vol 9 (5) ◽  
pp. 1525 ◽  
Author(s):  
Daphne C. Voormolen ◽  
Marina Zeldovich ◽  
Juanita A. Haagsma ◽  
Suzanne Polinder ◽  
Sarah Friedrich ◽  
...  

The objective of this study was to provide a comprehensive examination of the relation of complicated and uncomplicated mild traumatic brain injury (mTBI) with multidimensional outcomes at three- and six-months after TBI. We analyzed data from the Collaborative European NeuroTrauma Effectiveness Research (CENTER-TBI) research project. Patients after mTBI (Glasgow Coma scale (GCS) score of 13–15) enrolled in the study were differentiated into two groups based on computed tomography (CT) findings: complicated mTBI (presence of any traumatic intracranial injury on first CT) and uncomplicated mTBI (absence of any traumatic intracranial injury on first CT). Multidimensional outcomes were assessed using seven instruments measuring generic and disease-specific health-related quality of life (HRQoL) (SF-36 and QOLIBRI), functional outcome (GOSE), and psycho-social domains including symptoms of post-traumatic stress disorder (PTSD) (PCL-5), depression (PHQ-9), and anxiety (GAD-7). Data were analyzed using a multivariate repeated measures approach (MANOVA-RM), which inspected mTBI groups at three- and six-months post injury. Patients after complicated mTBI had significantly lower GOSE scores, reported lower physical and mental component summary scores based on the SF-36 version 2, and showed significantly lower HRQoL measured by QOLIBRI compared to those after uncomplicated mTBI. There was no difference between mTBI groups when looking at psychological outcomes, however, a slight improvement in PTSD symptoms and depression was observed for the entire sample from three to six months. Patients after complicated mTBI reported lower generic and disease specific HRQoL and worse functional outcome compared to individuals after uncomplicated mTBI at three and six months. Both groups showed a tendency to improve from three to six months after TBI. The complicated mTBI group included more patients with an impaired long-term outcome than the uncomplicated group. Nevertheless, patients, clinicians, researchers, and decisions-makers in health care should take account of the short and long-term impact on outcome for patients after both uncomplicated and complicated mTBI.


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