scholarly journals Immunological context of brain injury

2021 ◽  
Vol 23 (1) ◽  
pp. 163-168
Author(s):  
N. G. Plekhova ◽  
I. V. Radkov ◽  
S. V. Zinoviev ◽  
V. B. Shumatov
Keyword(s):  
Traumatic Brain Injury ◽  
T Cells ◽  
Brain Injury ◽  
Positive Reaction ◽  
Mild Traumatic Brain Injury ◽  
Brain Parenchyma ◽  
Post Injury ◽  
Blood Leukocytes ◽  
Subsequent Decrease ◽  
The Brain

The parameters of several populations of immune cells (T cell populations, macrophage subpopulations) in peripheral blood and brain were studied in a clinically significant model of mild traumatic brain injury among rats. The population of resident cells of innate immunity of microglia and brain astrocytes with local tissue damage is involved in the implementation of the inflammatory response, it is also shown that in case of trauma, blood leukocytes can overcome the blood-brain barrier and penetrate the brain parenchyma. The methods of flow cytometry and immunofluorescence were used. An increase in the number of monocytes and neutrophils up to 1 day, after a mild traumatic brain injury (TBI) with a subsequent decrease to the end of the observation period was noticed. It was determined, that the number of CD45+ cells, CD3+T cells decreased at 1 days post-injury (dpi), and rose slightly by 14 dpi, the percentage of CD4+T cells continuously declined from 7 to 14 dpi, while the percentage of CD8+T cells increased from 7 to 14 dpi. With mild traumatic brain injury in animals, a significant (3-10 times) decrease in the number of microvessels with a positive reaction to the presence of SMI 71 on the 8th and 14th day after head injury was observed. Intensive staining of SMI 71 microvessels was sometimes observed with an increase in the area of a positive reaction. Thin positive deposits of the reaction product are observed in the brain of healthy animals around the wall of the microvessel. In the damaged brain, CD45high/CD11b+ positive macrophages of the M1 subpopulation appeared in the brain tissue on the 2nd day after TBI and a significant amount was observed on the 8-14th day. In the corpus callosum and ipsilateral region of the striatum, the content of cells expressing CD16/11b+ reached a maximum 8 days after TBI, which correlated with a decrease in the positive response to the presence of endothelial antigen SMI 71. Thus, in the acute period of mild TBI, the presence of neuroimmunopathological processes is determined in the brain, which can subsequently result to the dysregulation of neuroimmune connections.

scholarly journals Diverse Changes in Microglia Morphology and Axonal Pathology Over One Year after Mild Traumatic Brain Injury in Pigs

2020 ◽  
Author(s):  
Michael R. Grovola ◽  
Nicholas Paleologos ◽  
Daniel P. Brown ◽  
Nathan Tran ◽  
Kathryn L. Wofford ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Mild Traumatic Brain Injury ◽  
Periventricular White Matter ◽  
Post Injury ◽  
Mild Tbi ◽  
Time Points ◽  
Axonal Pathology ◽  
The Brain

AbstractOver 2.8 million people experience mild traumatic brain injury (TBI) in the United States each year, which may lead to long-term neurological dysfunction. The mechanical forces that occur due to TBI propagate through the brain to produce diffuse axonal injury (DAI) and trigger secondary neuroinflammatory cascades. The cascades may persist from acute to chronic time points after injury, altering the homeostasis of the brain. However, the relationship between the hallmark axonal pathology of diffuse TBI and potential changes in glial cell activation or morphology have not been established in a clinically relevant large animal model at chronic time points. In this study, we assessed tissue from pigs subjected to rapid head rotation in the coronal plane to generate mild TBI. Neuropathological assessments for axonal pathology, microglial morphological changes, and astrocyte reactivity were conducted in specimens out to 1 year post injury. We detected an increase in overall amyloid precursor protein pathology, as well as periventricular white matter and fimbria/fornix pathology after a single mild TBI. We did not detect changes in corpus callosum integrity or astrocyte reactivity. However, detailed microglial skeletal analysis revealed changes in morphology, most notably increases in the number of microglial branches, junctions, and endpoints. These subtle changes were most evident in periventricular white matter and certain hippocampal subfields, and were observed out to 1 year post injury in some cases. These ongoing morphological alterations suggest persistent change in neuroimmune homeostasis. Additional studies are needed to characterize the underlying molecular and neurophysiological alterations, as well as potential contributions to neurological deficits.

scholarly journals The CNS lymphatic system modulates the adaptive neuro-immune response in the perilesional cortex in a mouse model of traumatic brain injury

2019 ◽  
Author(s):  
Wojciechowski Sara ◽  
Vihma Maria ◽  
Galbardi Barbara ◽  
Virenque Anaïs ◽  
Meike H. Keuters ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Immune Response ◽  
T Cells ◽  
Brain Injury ◽  
Lymphatic Vessels ◽  
Lesion Size ◽  
Lesion Volume ◽  
Post Injury ◽  
Circulating T Cells ◽  
The Brain

AbstractRationaleThe recently discovered meningeal lymphatic vessels (mLVs) have been proposed to be the missing link between the immune and the central nervous systems. The role of mLVs in modulating the neuro-immune response following a brain injury, however, has not been analyzed. Parenchymal T lymphocyte infiltration has been previously reported as part of secondary events after traumatic brain injury (TBI), suggestive of an adaptive neuro-immune response. The phenotype of these cells has remained mostly uncharacterized. In this study, we identified the subpopulations of T cells infiltrating the perilesional areas 30 days post-injury (an early-chronic time point). Furthermore, we analyzed how the lack of mLVs affects the magnitude and the type of immune response in the brain after TBI.MethodsTBI was induced in K14-VEGFR3-Ig transgenic (TG) mice or in their littermate controls (WT; wild type), applying a controlled cortical impact (CCI). One month after TBI, T cells were isolated from cortical areas ipsilateral or contralateral to the trauma and from the spleen, then characterized by flow cytometry. Lesion size in each animal was evaluated by MRI.ResultsIn both WT and TG-CCI mice, we found a prominent T cell infiltration in the brain confined to the perilesional cortex and hippocampus. The majority of infiltrating T cells were cytotoxic CD8+ expressing a CD44hiCD69+ phenotype, suggesting that these are effector resident memory T cells. K14-VEGFR3-Ig mice showed a significant reduction of infiltrating CD4+ T lymphocytes, implying that mLVs are important in establishing a proper neuro-immune response. Extension of the lesion (measured as lesion volume from MRI) did not differ between the genotypes. Finally, TBI did not relate with alterations in peripheral circulating T cells, as assessed one month after injury induction.ConclusionsOur data support the hypothesis that mLVs are pivotal for a proper and specific neuro-immune response after TBI, which is principally mediated by the resident memory CD8+ T cells.

scholarly journals Accelerated Brain Aging in Mild Traumatic Brain Injury: Longitudinal Pattern Recognition With White Matter Integrity

2020 ◽  
Author(s):  
Shuoqiu Gan ◽  
Wen Shi ◽  
Shan Wang ◽  
Yingxiang Sun ◽  
Bo Yin ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Prediction Model ◽  
Mild Traumatic Brain Injury ◽  
Aging Process ◽  
Brain Aging ◽  
Post Injury ◽  
Brain Age ◽  
The Brain ◽  
Age Prediction

Abstract Background: Long-term effects of mild traumatic brain injury (mTBI) resemble brain aging changes (i.e., microstructure integrity loss), which implies an accelerated age-associated process. This study aimed to develop a quantifiable neuroimaging marker to characterize the brain-aging process accelerated by mTBI from acute to chronic phases. Methods: A brain-age prediction model was defined using relevance vector regression (RVR) in 523 healthy individuals, based on fractional anisotropy metrics from diffusion-tensor imaging. The model was adopted to estimate brain-predicted age difference (brain-PAD = predicted brain age - chronological age) in 116 acute mTBI patients and 63 healthy controls (HCs). Fifty patients were followed up 6~12 month post-injury to evaluate the longitudinal changes in brain-PAD. Another mTBI group containing 70 acute patients were included as a replicated cohort. We investigated whether brain-PAD was greater in patients with elderly age, post-concussion complaints, and risky apolipoprotein E (APOE) genotype, and whether it had the potential to predict neuropsychological outcomes for information processing speed (IPS). Between-group and longitudinal comparison in brain-PAD was conducted with analysis of covariance and linear mixed-effects model, respectively. The correlation between brain-PAD and continuous variables was analyzed with Spearman rank-order correlation.Results: The RVR brain-age prediction model predicted brain age accurately (r = 0.96, R2 = 0.93). The brain age of mTBI patients was estimated to be "older" in the acute phase, with mean brain-PAD of 2.59 (± 5.97) years compared with HCs (0.12 ± 3.19 years) (P < 0.05) and replicated in another mTBI cohort (brain-PAD: 3.26 ± 4.55 years). The increased brain age in mTBI kept stable at 6-12 month post-injury (2.50 ± 4.54 years). Patients with older age or severer post-concussion complaints obtained greater brain-PAD (P < 0.001, P = 0.024), while patients with APOE ε4 didn’t obtain greater brain-PAD than those without. Additionally, brain-PAD in the acute phase predicted patients’ IPS profile at 6~12 month follow-up (rho = -0.36, P = 0.01). Conclusion: Mild TBI, even a single one, accelerates the brain-aging process. The brain-PAD can be considered as a quantitative neuroimaging marker to evaluate the susceptibility to neurodegeneration or other age-associated conditions following mTBI. Trial registration: NCT02868684.

Neuropsychological results and neuropathological findings at autopsy in a case of mild traumatic brain injury

2004 ◽  
Vol 10 (5) ◽  
pp. 794-806 ◽  
Author(s):  
ERIN D. BIGLER
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Short Term Memory ◽  
Microscopic Analysis ◽  
Residual Effects ◽  
Unexpected Death ◽  
Post Injury ◽  
Normal Limits ◽  
The Brain

Autopsy studies were undertaken in a 47-year-old college-educated male patient who, 7 months prior to an unexpected death, had sustained a mild traumatic brain injury (TBI) as manifested by brief loss of consciousness and an initial Glasgow Coma Scale score of 14. The patient died from cardiac arrest secondary to an undiagnosed and unknown arteriosclerotic cardiovascular disease as assessed by the coroner's office at the time of autopsy. Gross inspection of the brain at autopsy was normal; however, microscopic analysis demonstrated what were considered trauma findings of hemosiderin-laden macrophages in the perivascular space and macrophages in the white matter, particularly the section taken from the frontal lobe. The patient had partially returned to work at the time of death, but had encountered problems with diminished cognitive performance in his work as an appraiser. Neuropsychological studies were generally within normal limits although several tests of either speed of processing or short-term memory showed lower than expected performance. This case demonstrates the presence of subtle neuropathological changes in the brain of a patient who sustained a mild TBI and was still symptomatic for the residual effects of the injury 7 months post injury when he unexpectedly died. (JINS, 2004,10, 794–806.)

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 The Challenge of Managing Patients Suffering from TBI: The Utility of Multiparametric MRI

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 178-179
Author(s):  
John L. Sherman ◽  
Laurence J. Adams ◽  
Christen F. Kutz ◽  
Deborah York ◽  
Mitchell S. Szymczak
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Family History ◽  
Diffusion Tensor ◽  
Multiparametric Mri ◽  
Psychiatric History ◽  
Post Injury ◽  
Negative Family History ◽  
Imaging Result ◽  
The Brain

AbstractTraumatic brain injury (TBI) is a complex phenomenon affecting multiple areas of the brain in multiple ways. Both right and left hemispheres are affected as well as supratentorial and infratentorial compartments. These multifocal injuries are caused by many factors including acute mechanical injury, focal intracranial hemorrhage, blunt and rotational forces, epidural and subdural hematoma, hypoxemia, hypotension, edema, axonal damage, neuronal death, gliosis and blood brain barrier disruption. Clinicians and patients benefit by precise information about the neuroanatomical areas that are affected macroscopically, microscopically and biochemically in an individual patient.Standard imaging studies are frequently negative or grossly underestimate the severity of TBI and may exacerbate and prolong patient suffering with an imaging result of “no significant abnormality”. Specifically, sophisticated imaging tools have been developed which reveal significant damage to the brain structure including atrophy, MRI spectroscopy showing variations in neuronal metabolite N-acetyl-aspartate, elevations of membrane related Choline, and the glial metabolite myo-inositol is often observed to be increased post injury. In addition, susceptibility weighted imaging (SWI) has been shown to be more reliable for detecting microbleeds versus calcifications.We have selected two TBI patients with diffuse traumatic brain injury.The first patient is a 43-year-old male who suffered severe traumatic brain injury from a motorcycle accident in 2016. Following the accident, the patient was diagnosed with seizures, major depression, and intermittent explosive disorder. He has attempted suicide and has neurobehavioral disinhibition including severe anger, agitation and irritability. He denies psychiatric history prior to TBI and has negative family history. Following the TBI, he became physically aggressive and assaultive in public with minimal provocation. He denies symptoms of thought disorder and mania. He is negative for symptoms of  cognitive decline or encephalopathy.The second patient is a 49-year-old male who suffered at least 3 concussive blasts in the Army and a parachute injury. Following the last accident, the patient was diagnosed with major depressive disorder, panic disorder, PTSD and generalized anxiety disorder. He denies any psychiatric history prior to TBI including negative family history of psychiatric illness. In addition, he now suffers from nervousness, irritability, anger, emotional lability and concurrent concentration issues, problems completing tasks and alterations in memory.Both patients underwent 1.5T multiparametric MRI using standard T2, FLAIR, DWI and T1 sequences, and specialized sequences including susceptibility weighted (SWAN/SWI), 3D FLAIR, single voxel MRI spectroscopy (MRS), diffusion tensor imaging (DTI), arterial spin labeling perfusion (ASL) and volumetric MRI (NeuroQuant). Importantly, this exam can be performed in 30–45 minutes and requires no injections other than gadolinium in some patients. We will discuss the insights derived from the MRI which detail the injured areas, validate the severity of the brain damage, and provide insight into the psychological, motivational and physical disabilities that afflict these patients. It is our expectation that this kind of imaging study will grow in value as we link specific patterns of injury to specific symptoms and syndromes resulting in more targeted therapies in the future.

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.

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.

Severity of Ongoing Post-Concussive Symptoms as a Predictor of Cognitive Performance Following a Pediatric Mild Traumatic Brain Injury

2020 ◽  
pp. 1-11
Author(s):  
Veronik Sicard ◽  
Danielle C. Hergert ◽  
Sharvani Pabbathi Reddy ◽  
Cidney R. Robertson-Benta ◽  
Andrew B. Dodd ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cognitive Performance ◽  
Mild Traumatic Brain Injury ◽  
Parental Education ◽  
Visual Learning ◽  
Learning Task ◽  
Risk Scores ◽  
Group Differences ◽  
Post Injury

Abstract Objective: This study aimed to examine the predictors of cognitive performance in patients with pediatric mild traumatic brain injury (pmTBI) and to determine whether group differences in cognitive performance on a computerized test battery could be observed between pmTBI patients and healthy controls (HC) in the sub-acute (SA) and the early chronic (EC) phases of injury. Method: 203 pmTBI patients recruited from emergency settings and 159 age- and sex-matched HC aged 8–18 rated their ongoing post-concussive symptoms (PCS) on the Post-Concussion Symptom Inventory and completed the Cogstate brief battery in the SA (1–11 days) phase of injury. A subset (156 pmTBI patients; 144 HC) completed testing in the EC (∼4 months) phase. Results: Within the SA phase, a group difference was only observed for the visual learning task (One-Card Learning), with pmTBI patients being less accurate relative to HC. Follow-up analyses indicated higher ongoing PCS and higher 5P clinical risk scores were significant predictors of lower One-Card Learning accuracy within SA phase, while premorbid variables (estimates of intellectual functioning, parental education, and presence of learning disabilities or attention-deficit/hyperactivity disorder) were not. Conclusions: The absence of group differences at EC phase is supportive of cognitive recovery by 4 months post-injury. While the severity of ongoing PCS and the 5P score were better overall predictors of cognitive performance on the Cogstate at SA relative to premorbid variables, the full regression model explained only 4.1% of the variance, highlighting the need for future work on predictors of cognitive outcomes.

Sign in / Sign up

Export Citation Format

Share Document