-
Journal of Neuroinflammation May 2024Epidemiological studies have unveiled a robust link between exposure to repetitive mild traumatic brain injury (r-mTBI) and elevated susceptibility to develop...
Overexpression of pathogenic tau in astrocytes causes a reduction in AQP4 and GLT1, an immunosuppressed phenotype and unique transcriptional responses to repetitive mild TBI without appreciable changes in tauopathy.
Epidemiological studies have unveiled a robust link between exposure to repetitive mild traumatic brain injury (r-mTBI) and elevated susceptibility to develop neurodegenerative disorders, notably chronic traumatic encephalopathy (CTE). The pathogenic lesion in CTE cases is characterized by the accumulation of hyperphosphorylated tau in neurons around small cerebral blood vessels which can be accompanied by astrocytes that contain phosphorylated tau, the latter termed tau astrogliopathy. However, the contribution of tau astrogliopathy to the pathobiology and functional consequences of r-mTBI/CTE or whether it is merely a consequence of aging remains unclear. We addressed these pivotal questions by utilizing a mouse model harboring tau-bearing astrocytes, GFAP mice, subjected to our r-mTBI paradigm. Despite the fact that r-mTBI did not exacerbate tau astrogliopathy or general tauopathy, it increased phosphorylated tau in the area underneath the impact site. Additionally, gene ontology analysis of tau-bearing astrocytes following r-mTBI revealed profound alterations in key biological processes including immunological and mitochondrial bioenergetics. Moreover, gene array analysis of microdissected astrocytes accrued from stage IV CTE human brains revealed an immunosuppressed astroglial phenotype similar to tau-bearing astrocytes in the GFAP model. Additionally, hippocampal reduction of proteins involved in water transport (AQP4) and glutamate homeostasis (GLT1) was found in the mouse model of tau astrogliopathy. Collectively, these findings reveal the importance of understanding tau astrogliopathy and its role in astroglial pathobiology under normal circumstances and following r-mTBI. The identified mechanisms using this GFAP model may suggest targets for therapeutic interventions in r-mTBI pathogenesis in the context of CTE.
Topics: Astrocytes; Animals; Mice; tau Proteins; Aquaporin 4; Tauopathies; Humans; Excitatory Amino Acid Transporter 2; Mice, Transgenic; Brain Concussion; Male; Phenotype; Mice, Inbred C57BL
PubMed: 38750510
DOI: 10.1186/s12974-024-03117-4 -
Sensors (Basel, Switzerland) May 2024Concussions, a prevalent public health concern in the United States, often result from mild traumatic brain injuries (mTBI), notably in sports such as American football....
Concussions, a prevalent public health concern in the United States, often result from mild traumatic brain injuries (mTBI), notably in sports such as American football. There is limited exploration of smart-textile-based sensors for measuring the head impacts associated with concussions in sports and recreational activities. In this paper, we describe the development and construction of a smart textile impact sensor (STIS) and validate STIS functionality under high magnitude impacts. This STIS can be inserted into helmet cushioning to determine head impact force. The designed 2 × 2 STIS matrix is composed of a number of material layered structures, with a sensing surface made of semiconducting polymer composite (SPC). The SPC dimension was modified in the design iteration to increase sensor range, responsiveness, and linearity. This was to be applicable in high impact situations. A microcontroller board with a biasing circuit was used to interface the STIS and read the sensor's response. A pendulum test setup was constructed to evaluate various STISs with impact forces. A camera and Tracker software were used to monitor the pendulum swing. The impact forces were calculated by measuring the pendulum bob's velocity and acceleration. The performance of the various STISs was measured in terms of voltage due to impact force, with forces varying from 180 to 722 N. Through data analysis, the threshold impact forces in the linear range were determined. Through an analysis of linear regression, the sensors' sensitivity was assessed. Also, a simplified model was developed to measure the force distribution in the 2 × 2 STIS areas from the measured voltages. The results showed that improving the SPC thickness could obtain improved sensor behavior. However, for impacts that exceeded the threshold, the suggested sensor did not respond by reflecting the actual impact forces, but it gave helpful information about the impact distribution on the sensor regardless of the accurate expected linear response. Results showed that the proposed STIS performs satisfactorily within a range and has the potential to be used in the development of an e-helmet with a large STIS matrix that could cover the whole head within the e-helmet. This work also encourages future research, especially on the structure of the sensor that could withstand impacts which in turn could improve the overall range and performance and would accurately measure the impact in concussion-causing impact ranges.
Topics: Textiles; Head Protective Devices; Humans; Craniocerebral Trauma; Brain Concussion; Equipment Design
PubMed: 38733025
DOI: 10.3390/s24092919 -
International Journal of Molecular... Apr 2024Concussion, caused by a rotational acceleration/deceleration injury mild enough to avoid structural brain damage, is insufficiently captured in recent preclinical...
Concussion, caused by a rotational acceleration/deceleration injury mild enough to avoid structural brain damage, is insufficiently captured in recent preclinical models, hampering the relation of pathophysiological findings on the cellular level to functional and behavioral deficits. We here describe a novel model of unrestrained, single vs. repetitive concussive brain injury (CBI) in male C56Bl/6j mice. Longitudinal behavioral assessments were conducted for up to seven days afterward, alongside the evaluation of structural cerebral integrity by in vivo magnetic resonance imaging (MRI, 9.4 T), and validated ex vivo by histology. Blood-brain barrier (BBB) integrity was analyzed by means of fluorescent dextran- as well as immunoglobulin G (IgG) extravasation, and neuroinflammatory processes were characterized both in vivo by positron emission tomography (PET) using [F]DPA-714 and ex vivo using immunohistochemistry. While a single CBI resulted in a defined, subacute neuropsychiatric phenotype, longitudinal cognitive testing revealed a marked decrease in spatial cognition, most pronounced in mice subjected to CBI at high frequency (every 48 h). Functional deficits were correlated to a parallel disruption of the BBB, (R = 0.29, < 0.01), even detectable by a significant increase in hippocampal uptake of [F]DPA-714, which was not due to activation of microglia, as confirmed immunohistochemically. Featuring a mild but widespread disruption of the BBB without evidence of macroscopic damage, this model induces a characteristic neuro-psychiatric phenotype that correlates to the degree of BBB disruption. Based on these findings, the BBB may function as both a biomarker of CBI severity and as a potential treatment target to improve recovery from concussion.
Topics: Animals; Blood-Brain Barrier; Mice; Brain Concussion; Disease Models, Animal; Male; Mice, Inbred C57BL; Magnetic Resonance Imaging; Positron-Emission Tomography; Head Injuries, Closed
PubMed: 38732053
DOI: 10.3390/ijms25094837 -
Human Brain Mapping May 2024With the steadily increasing abundance of longitudinal neuroimaging studies with large sample sizes and multiple repeated measures, questions arise regarding the...
With the steadily increasing abundance of longitudinal neuroimaging studies with large sample sizes and multiple repeated measures, questions arise regarding the appropriate modeling of variance and covariance. The current study examined the influence of standard classes of variance-covariance structures in linear mixed effects (LME) modeling of fMRI data from patients with pediatric mild traumatic brain injury (pmTBI; N = 181) and healthy controls (N = 162). During two visits, participants performed a cognitive control fMRI paradigm that compared congruent and incongruent stimuli. The hemodynamic response function was parsed into peak and late peak phases. Data were analyzed with a 4-way (GROUP×VISIT×CONGRUENCY×PHASE) LME using AFNI's 3dLME and compound symmetry (CS), autoregressive process of order 1 (AR1), and unstructured (UN) variance-covariance matrices. Voxel-wise results dramatically varied both within the cognitive control network (UN>CS for CONGRUENCY effect) and broader brain regions (CS>UN for GROUP:VISIT) depending on the variance-covariance matrix that was selected. Additional testing indicated that both model fit and estimated standard error were superior for the UN matrix, likely as a result of the modeling of individual terms. In summary, current findings suggest that the interpretation of results from complex designs is highly dependent on the selection of the variance-covariance structure using LME modeling.
Topics: Humans; Magnetic Resonance Imaging; Male; Female; Adolescent; Child; Brain Concussion; Linear Models; Brain; Brain Mapping; Executive Function
PubMed: 38726907
DOI: 10.1002/hbm.26699 -
Cureus Apr 2024Primary hyperparathyroidism (PHPT) is an extremely uncommon cause of cerebral calcification. A male patient, aged 45, was admitted to the neurosurgery clinic with a...
Primary hyperparathyroidism (PHPT) is an extremely uncommon cause of cerebral calcification. A male patient, aged 45, was admitted to the neurosurgery clinic with a closed traumatic brain injury, namely a concussion, resulting in symptoms of headache and loss of balance. A CT scan was conducted, which detected bilateral calcifications on the basal ganglia and the tentorium. The blood tests revealed increased levels of serum calcium, phosphate, and parathyroid hormone (PTH), while vitamin D levels were within the normal range. The patient received symptomatic therapy for the cerebral concussion and was referred for further diagnostic procedures. Based on these exams, it was determined that the patient had a parathyroid adenoma, which was responsible for PHPT characterised by increased levels of calcium, phosphate, and PTH. The patient subsequently underwent a successful parathyroidectomy. Half a year following the surgical procedure, the patient remained free of any indications of neurological conditions, and the levels of PTH and calcium in their body were within the expected range. Whenever trying to identify the cause of cerebral calcification, it is important to explore several possible diagnoses. A possible cause that should be taken into account is PHTP.
PubMed: 38721190
DOI: 10.7759/cureus.57826 -
British Journal of Sports Medicine May 2024
PubMed: 38719575
DOI: 10.1136/bjsports-2023-107413 -
Fortune Journal of Health Sciences 2024A concussion is a particular manifestation of a traumatic brain injury, which is the leading cause of mortality and disabilities across the globe. The global prevalence...
A concussion is a particular manifestation of a traumatic brain injury, which is the leading cause of mortality and disabilities across the globe. The global prevalence of traumatic brain injury is estimated to be 939 instances per 100,000 individuals, with approximately 5.48 million people per year experiencing severe traumatic brain injury. Epidemiology varies amongst different countries by socioeconomic status with diverse clinical manifestations. Additionally, classifying concussions is an ambiguous process as clinical diagnoses are the only current classification method, and morbidity rates differ by demographic location as well as populations examined. In this article, we critically reviewed the pathophysiology of concussions, classification methods, treatment options available including both pharmacologic and nonpharmacologic intervention methods, etiologies as well as global etiologic differences associated with them, and clinical manifestations along with their associated morbidities. Furthermore, analysis of the current research regarding the incidence of concussion based traumatic brain injuries and future directions are discussed. Investigation on the efficacy of new therapeutic-related interventions such as exosome therapy and electromagnetic field stimulation are warranted to properly manage and treat concussion-induced traumatic brain injury.
PubMed: 38708028
DOI: 10.26502/fjhs.178 -
Acta Neuropathologica May 2024Although human females appear be at a higher risk of concussion and suffer worse outcomes than males, underlying mechanisms remain unclear. With increasing recognition...
Although human females appear be at a higher risk of concussion and suffer worse outcomes than males, underlying mechanisms remain unclear. With increasing recognition that damage to white matter axons is a key pathologic substrate of concussion, we used a clinically relevant swine model of concussion to explore potential sex differences in the extent of axonal pathologies. At 24 h post-injury, female swine displayed a greater number of swollen axonal profiles and more widespread loss of axonal sodium channels than males. Axon degeneration for both sexes appeared to be related to individual axon architecture, reflected by a selective loss of small caliber axons after concussion. However, female brains had a higher percentage of small caliber axons, leading to more extensive axon loss after injury compared to males. Accordingly, sexual dimorphism in axonal size is associated with more extensive axonal pathology in females after concussion, which may contribute to worse outcomes.
Topics: Animals; Female; Axons; Brain Concussion; Male; Sex Characteristics; Disease Models, Animal; Swine; Brain
PubMed: 38705966
DOI: 10.1007/s00401-024-02735-9 -
Ugeskrift For Laeger Apr 2024Mild traumatic brain injury, such as concussion, was once considered self-resolving. However, over the past decade, increased understanding of the short- and long-term... (Review)
Review
Mild traumatic brain injury, such as concussion, was once considered self-resolving. However, over the past decade, increased understanding of the short- and long-term impact has led to new guidelines for active management. In this review, we summarise recent findings, covering diagnostic criteria, and management for early and persistent symptoms. Many of the postconcussive symptoms can be treated and an individualised approach from a biopsychosocial perspective is recommended. Overall, the new knowledge will significantly impact patient care and future research.
Topics: Humans; Brain Concussion; Post-Concussion Syndrome; Athletic Injuries
PubMed: 38704707
DOI: 10.61409/V10230645 -
Scientific Reports May 2024The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome has been associated with worse outcomes from severe traumatic brain injury (TBI). The NLRP3...
The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome has been associated with worse outcomes from severe traumatic brain injury (TBI). The NLRP3 inflammasome is also strongly associated with other pro-inflammatory conditions, such as obesity. Little is known about the potential effect of mild TBI (mTBI) on the NLRP3 inflammasome and the extent to which modifying factors, such as obesity, may augment the inflammatory response to mTBI. The purpose of this study was to evaluate the association of NLRP3 inflammasome proteins with obese body mass index (BMI ≥ 30) within 24 h of mTBI after presenting to a level 1 trauma center emergency department. This is a secondary analysis of prospectively enrolled patients with mTBI who presented to the emergency department of one U.S. Level 1 trauma center from 2013 to 2018 (n = 243). A series of regression models were built to evaluate the association of NLRP3 proteins obtained from blood plasma within 24 h of injury and BMI as well as the potential interaction effect of higher BMI with NLRP3 proteins (n = 243). A logistic regression model revealed a significant association between IL-18 (p < 0.001) in mTBI patients with obese BMI compared to mTBI patients with non-obese BMI (< 30). Moderation analyses revealed statistically significant interaction effects between apoptotic speck-like protein (ASC), caspase-1, IL-18, IL-1β and obese BMI which worsened symptom burden, quality of life, and physical function at 2 weeks and 6 months post-injury. Higher acute concentrations of IL-1β in the overall cohort predicted higher symptoms at 6-months and worse physical function at 2-weeks and 6-months. Higher acute concentrations of IL-18 in the overall cohort predicted worse physical function at 6-months. In this single center mTBI cohort, obese BMI interacted with higher acute concentrations of NLRP3 inflammasome proteins and worsened short- and long-term clinical outcomes.
Topics: Humans; NLR Family, Pyrin Domain-Containing 3 Protein; Male; Female; Obesity; Inflammasomes; Adult; Middle Aged; Brain Concussion; Body Mass Index; Interleukin-18; Prospective Studies; Interleukin-1beta; Caspase 1
PubMed: 38702410
DOI: 10.1038/s41598-024-61089-0