Arterial carbon dioxide (pCO) strongly affects cerebrovascular tone and cerebral physiology. While moderate hyperventilation is often used to reduce intracranial pressure (ICP) in acute brain injury, its broader physiolo...Arterial carbon dioxide (pCO) strongly affects cerebrovascular tone and cerebral physiology. While moderate hyperventilation is often used to reduce intracranial pressure (ICP) in acute brain injury, its broader physiological effects remain unclear. In this experimental study, 10 anesthetized pigs underwent multimodal neuromonitoring, including ICP, cerebral perfusion pressure, common autoregulatory indices (pressure reactivity index [PRx], cerebral blood flow index [CBFx], oxygen reactivity index), CBF, brain tissue oxygenation (pbtO), and microdialysis. Animals were exposed to four ventilatory intervals (normoventilation, moderate and severe hyperventilation, and hypoventilation), first in a healthy state and then following induction of intracranial hypertension (ICP 30-40 mmHg) via epidural balloon inflation. In the , moderate and severe hyperventilation numerically, but non-significantly, reduced CBF without affecting pbtO or cerebral energy metabolism, while hypoventilation increased CBF and pbtO. Under intracranial hypertension, moderate hyperventilation improved PRx and preserved CBF, pbtO, and metabolism, but severe hyperventilation reduced pbtO. Hypoventilation produced variable responses: Animals with higher baseline blood pressure showed improved perfusion and oxygenation, whereas those with lower pressure experienced reduced CBF, impaired oxygenation, and metabolic distress. These findings underscore the complex and context-dependent effects of pCO on cerebral physiology, indicating that ventilatory strategies may both benefit and harm the injured brain depending on individual vulnerability and hemodynamic status.
Silverberg ND, Lee K, Mikolić A
… +16 more, Bayley MT, Brody DL, Ely EW, Giacino JT, Halabi C, Hammond FM, Ignacio DA, Mosti C, van der Naalt J, Pappadis MR, Ravi A, Tenovuo O, Wang VY, Verduzco-Gutierrez M, Manley GT, Action Collaborative on TBI Care
Outpatient follow-up care for traumatic brain injury (TBI) is inconsistent. The Action Collaborative on TBI Care, convened under the auspices of the National Academies of Sciences, Engineering, and Medicine, aimed to sta...Outpatient follow-up care for traumatic brain injury (TBI) is inconsistent. The Action Collaborative on TBI Care, convened under the auspices of the National Academies of Sciences, Engineering, and Medicine, aimed to standardize management with a clinical practice guideline. The guideline is intended for community-dwelling adults with TBI who are able to care for themselves at hospital discharge or who did not require acute hospital care. Guideline topics were selected and prioritized with input from individuals with lived experience and clinicians. Existing evidence-based clinical practice guidelines ( = 18) were identified from systematic literature reviews. Recommendations for each priority topic were extracted from existing guidelines and synthesized using the ADAPTE process. Strength of evidence ratings were assigned based on the American Academy of Family Physician's adaptation of GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) through consensus voting. A draft guideline underwent external review by 20 health professional and brain injury organizations. The Action Collaborative on TBI Care guideline provides recommendations for 11 priority topics: (1) confirm the diagnosis; (2) determine whether emergency department evaluation is required; (3) request neuroimaging and neuropsychological assessment when indicated; (4) screen for social determinants of health; (5) provide guidance on return to usual activities; (6) educate the patient and family; (7) assess for risk of persistent symptoms; (8) prioritize which symptoms to target first; (9) initiate treatment for posttraumatic headache; (10) screen and initiate treatment for mental health disorders; and (11) decide if and when to refer to specialty care.
Hoffman JM, Obata T, Ciol MA
… +13 more, Humbert A, Bogner J, Corrigan JD, Dams-O'Connor K, Driver S, Dubiel R, Hammond FM, Hart T, Kajankova M, Moore M, Watanabe TK, Whyte J, Fann JR
J Neurotrauma
· 2026 Jan · PMID 40960892
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Moderate to severe traumatic brain injury (msTBI) results in physical, cognitive, behavioral, and psychosocial difficulties. Those who receive inpatient rehabilitation following a msTBI need assistance after discharge. P...Moderate to severe traumatic brain injury (msTBI) results in physical, cognitive, behavioral, and psychosocial difficulties. Those who receive inpatient rehabilitation following a msTBI need assistance after discharge. Patients and their families often struggle to find information, manage symptoms, and identify and access relevant services. Inadequate transition services from hospital-based care to the community can perpetuate and amplify the consequences of msTBI. There is a critical need for enhanced transitional care following hospital discharge. The goal of the current study was to compare two existing models for supporting the transition in the United States: 1. The Commission on Accreditation of Rehabilitation Facilities (CARF) model focused on transition planning prior to discharge (denominated Rehabilitation Discharge Plan [RDP]) and 2. The Veterans Health Administration model which provides a more intensive approach, extending beyond discharge, to enhance transitional care services (denominated Rehabilitation Transition Plan [RTP]). A six-center, 1:1 randomized pragmatic clinical trial with masked outcome assessment was conducted to compare the effectiveness of these two approaches. All participants received the RDP, including: 1. Patient and family education; 2. Written discharge instructions reviewed with the patient and family prior to discharge; and 3. A brief phone call from an inpatient care provider post discharge to identify any immediate problems. Those randomized to the RTP intervention also received up to 12 scheduled contacts during the 6 months following discharge from a trained care manager to assess needs, provide education, and resource facilitation. The primary outcomes were societal participation (participation assessment with recombined tools-objective) and quality of life (quality of life after brain injury scale) at 6 months post discharge. We hypothesized that patients randomized to RTP would report better participation and health-related quality of life (HRQoL) at the end of intervention and at 1-year post discharge compared with patients randomized to RDP. Second, we hypothesized that patients randomized to RTP would experience a steeper trajectory of improvement in participation and HRQoL over 12 months compared to patients randomized to RDP. A total of 925 patients were randomized. The results showed no significant differences between the two interventions on societal participation or HRQoL. Likewise, analysis of trajectory of outcomes did not show treatment group differences, and most patient participants had minimal change across all time points. Preinjury limitations, Medicaid insurance, and lower function contributed to worse outcomes but there was evidence for an interaction with the intervention for clinical sites and whether participants had an enrolled caregiver, which differed by group (increased participation with no enrolled caregiver in RTP, and better HRQoL with a caregiver for RDP). A key limitation of the study was the length of the intervention, with our patient, family, and professional partners reporting that 6 months might be insufficient to address the many needs that arise after msTBI.
The objective of this study was to compare the effectiveness of Brock string vision therapy (BSVT) with usual care (UC) for receded near point of convergence (NPC) following concussion. This study employed a single-blind...The objective of this study was to compare the effectiveness of Brock string vision therapy (BSVT) with usual care (UC) for receded near point of convergence (NPC) following concussion. This study employed a single-blind, randomized controlled trial design involving participants aged 11-30 years within 10 days of a concussion. Participants with receded NPC (i.e., mean NPC ≥5 cm) were randomized to either BSVT or UC. The BSVT group was prescribed BSVT exercises (5 reps, 2× daily, using ∼3 meters string with three colored beads). The UC group was prescribed symptom-specific management strategies (i.e., breaks during reading or other visual tasks) and behavioral management (e.g., sleep, hydration, diet) until follow-up (7-14 days post-enrollment). Two-way mixed effects analyses of variance examined the interaction between group (BSVT, UC) and time (enrollment, follow-up) on mean NPC (primary outcome) and secondary outcomes (e.g., Concussion Clinical Profile Screen [CP Screen]). Fifty participants were enrolled, with 25 in BSVT (age = 15.8 ± 4.1, 44% F, 84% sport-related concussion [SRC]) and 25 in UC (age = 17.9 ± 4.8, 36% F, 60% SRC). Results supported an interaction in the BSVT group for NPC (F[1, 48] = 5.3, = 0.026, η = 0.10) and CP Screen Neck (F[1, 43] = 4.9, = 0.033, η = 0.10). The BSVT group exhibited greater improvement in mean NPC distance (-8.9 cm, 95% confidence interval [CI] = -12.1, -5.7, < 0.001) than the UC group (-3.8 cm, 95% CI = -6.9, -0.6, = 0.02), and greater improvement in CP Screen Neck symptoms (-0.6, 95% CI, -1.1, -0.03, = 0.039) than the UC group (0.27, 95% CI, -0.3, 0.8, = 0.32). BSVT improved mean NPC distance compared with UC, suggesting that this simple, inexpensive, and early intervention may be effective for treating receded NPC following concussion. www.clinicaltrials.gov; identifier: NCT04076657.
Gangolli M, Nadar P, Marinelli L
… +2 more, Basser PJ, Avram AV
J Neurotrauma
· 2025 Nov · PMID 40930713
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Mean apparent propagator MRI (MAP-MRI) quantifies subtle alterations in tissue microstructure noninvasively and provides a more nuanced and comprehensive assessment of tissue architectural and structural integrity compar...Mean apparent propagator MRI (MAP-MRI) quantifies subtle alterations in tissue microstructure noninvasively and provides a more nuanced and comprehensive assessment of tissue architectural and structural integrity compared with other diffusion MRI techniques. We investigate the sensitivity of MAP-MRI-derived quantitative imaging biomarkers to detect previously unseen microstructural damage in patients with mild traumatic brain injuries (mTBI), whose clinical scans otherwise appeared normal. We developed and validated an MAP-MRI data processing pipeline for analyzing diffusion-weighted images for use in healthy controls and mTBI patients whose longitudinal scans were obtained from the GE/NFL/mTBI MRI database. A regional outlier analysis of longitudinal tissue changes in a pilot cohort during a 90-day period of observation showed that several MAP-MRI-derived parameters had increased intersession variability in white matter tracts and deep gray matter nuclei of mTBI patients relative to healthy controls. In summary, longitudinal monitoring of changes in MAP-MRI metrics may provide a comprehensive means to study pathological mTBI alterations that evolve at different timescales, while current image-based biomarkers lack the sensitivity and specificity and are unable to predict patient outcome.
Sherman BC, Schmidt Read M, Hoh DJ
… +3 more, Guest JD, Lane MA, Zholudeva LV
J Neurotrauma
· 2025 Dec · PMID 40929022
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Spinal cord injury (SCI) results in an array of debilitating, sometimes permanent-and at times life-threatening-motor, sensory, and autonomic deficits. A broad range of therapies have been tested pre-clinically, and ther...Spinal cord injury (SCI) results in an array of debilitating, sometimes permanent-and at times life-threatening-motor, sensory, and autonomic deficits. A broad range of therapies have been tested pre-clinically, and there has been a significant acceleration in recent years of clinical translation of potential treatments. However, it is widely appreciated among scientists and clinical professionals alike that there likely is no "silver bullet" (single treatment) that will result in complete functional restoration after SCI. The combination of more than one treatment approach, especially treatments that can have distinct beneficial effects, increases the probability of functional improvement. This review highlights the mounting interest in the pre-clinical development and application of combination strategies to treat SCI, and some of the translational efforts made to combine promising therapies for clinical evaluation. Special attention is given to barriers and limitations faced in translating treatments for people living with SCI.
Shiravi S, Yufa A, Papavasileiou P
… +5 more, Lotz S, Murphy D, Bertucci T, Temple S, Finan JD
J Neurotrauma
· 2025 Nov · PMID 40900146
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Traumatic brain injury (TBI) is the most important environmental risk factor for neurodegenerative disease. Tauopathy plays an important role in post-traumatic neurodegeneration. Human-induced pluripotent stem cell (hiPS...Traumatic brain injury (TBI) is the most important environmental risk factor for neurodegenerative disease. Tauopathy plays an important role in post-traumatic neurodegeneration. Human-induced pluripotent stem cell (hiPSC)-derived cortical organoids have exciting potential to reveal the influence of genotype on post-traumatic neurodegeneration because they permit manipulation of the genome in a human system. This study established an isogenic 3D cortical organoid model of TBI to investigate tau pathology and other clinically relevant injury phenotypes. Organoids generated from patient-derived hiPSC lines carrying the V337M or IVS10 + 16 Microtubule associated protein tau () mutations and their clustered regularly interspaced short palindromic repeats (CRISPR)-corrected isogenic counterparts were subjected to consistent compressive injury. Mitochondrial dysfunction, cell viability, lactate dehydrogenase (LDH) release, neurofilament light chain (NF-L) release, tau hyperphosphorylation, and tau oligomerization were quantified using live-cell imaging, ELISA, Western blotting, and immunostaining post-injury. Pathology depended on the severity of the mechanical injury and the time since injury. The V337M mutation synergized with injury to exacerbate cell damage, increasing LDH release and reducing viability in 4- and 6-month-old organoids. Therefore, this model can reproduce gene-trauma interactions so it has the capacity to answer important questions about why different patients have different outcomes after similar TBIs. mutation was not necessary for injury to induce tau hyperphosphorylation in 4-month-old organoids and both tau hyperphosphorylation and tau oligomerization in 6-month-old organoids. This capacity to induce advanced tau pathology in wild-type human organoids could have utility beyond the field of TBI research.
Cerebrovascular autoregulation (CA) is a protective mechanism against brain injury. We present an ultrasound-based volumetric blood flow indices to monitor CA. Swine were instrumented under general anesthesia to monitor...Cerebrovascular autoregulation (CA) is a protective mechanism against brain injury. We present an ultrasound-based volumetric blood flow indices to monitor CA. Swine were instrumented under general anesthesia to monitor mean arterial blood pressure (MAP), intracranial pressure (ICP), and blood flow in the internal carotid artery (ICA) and femoral artery (FA) and flow velocity and volumetric flow in the middle cerebral artery (MCA) using transcranial Doppler. Animals were subjected to several physiological challenges to perturb cerebral pressure and flow hemodynamics as follows: (1) Vasopressor challenge by controlled infusion of norepinephrine to raise MAP to 150-160 mmHg, followed by its down titration. (2) Epidural hematoma by inflating a subdurally-placed balloon to raise ICP to 35-45 mmHg, followed by deflation of the balloon. (3) Hemorrhage and resuscitation by controlled removal of the blood from jugular vein. After a 10-15 min period of hypovolemia, resuscitated started to raise MAP to 65 mmHg. Pressure reactivity index (PRx) was calculated as a moving Pearson correlation coefficient between MAP and ICP. The flow/flow indices [FFx(s)] were calculated as a moving Pearson correlation coefficient between FA blood flow and one of the following (mean flow velocity in the MCA, relative volumetric flow in the MCA and blood flow in the ICA). FFx(s) were compared to PRx using area under the receiver operator characteristic curve (AUROC) and the precision recall curve (AUPRC). FFx(s) demonstrated AUPRC and AUROC ranges (0.88-0.91) and (0.73-0.79). The FFx(s) can act as excellent potential surrogates for the PRx for the assessments of CA.
Stamper CE, Cominski TP, Hoisington AJ
… +9 more, Yoe CW, Agbolou XM, Stiritz VA, Interian A, Goodman M, Hazlett EA, Myers CE, Beck KD, Brenner LA
J Neurotrauma
· 2026 Jan · PMID 40899103
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Traumatic brain injuries (TBI) frequently occur and can lead to lasting negative cognitive, physical, and mental health outcomes. The biological response to even mild TBIs (mTBI) includes well-characterized inflammatory...Traumatic brain injuries (TBI) frequently occur and can lead to lasting negative cognitive, physical, and mental health outcomes. The biological response to even mild TBIs (mTBI) includes well-characterized inflammatory sequelae that start immediately post-injury, remain for weeks, and can develop into long-term systemic inflammation. Studies have shown that TBI influences multiple physiological systems, including the gastrointestinal tract, through bidirectional communication modulated, in part, by the gut microbiome. Brainstem functioning post-TBI, as measured by acoustic startle sensorimotor processing, might play a role in this feedback loop. The current study investigated pre- to post-TBI (lateral fluid percussion injury model) changes in microbial communities and acoustic startle response in male and female rats. That is, the influence of mTBI on gut microbiome and sensorimotor processing was explored to examine: 1) overall and sex-specific differences in the gut microbiome and taxa in response to mTBI; 2) overall and sex-specific differences in sensorimotor processing following mTBI; and 3) associations between the gut microbiome and sensorimotor processing. Results showed mTBI had a limited effect on microbial diversity overall, and the same was observed in males and females independently. Yet, mTBI was associated with differences in 13 genus-level taxa. Further evaluation highlighted that 11 of the 13 genus-level taxa were sex-specific, with several being known to have short-chain fatty acid-producing capabilities. Alterations in sensorimotor processing were identified following mTBI; however, no sex-specific differences were evident. In addition, no associations were observed between sensorimotor processing and the gut microbiome. This study contributes longitudinal and sex-specific findings to the growing body of research examining the diverse effects of mTBI on the brain and gut microbial communities.
Adverse childhood experiences (ACEs) and traumatic brain injuries (TBI) are highly prevalent globally, and both are associated with long-term negative health outcomes across the lifespan. Past research exploring the pote...Adverse childhood experiences (ACEs) and traumatic brain injuries (TBI) are highly prevalent globally, and both are associated with long-term negative health outcomes across the lifespan. Past research exploring the potential association between ACEs and TBI occurrence has demonstrated mixed findings. Thus, we conducted a systematic review and meta-analysis to examine the association between the ACEs measure and TBI occurrence. Moderator analyses were conducted to determine whether certain factors, including participant age, sex, and geographical location, modified the association between ACEs score and TBI occurrence. Searches were conducted in PsycINFO, MEDLINE, Embase, and CINHAL for studies published between January 1, 1998, and February 19, 2024. A total of 42 full-text articles were screened against inclusion criteria (i.e., measure of ACEs using the original 8- or 10-item scale or another composite measure of ACEs, TBI occurrence, and effect size for the association between ACEs score and TBI). Eight studies and 10 samples ( = 4954) were included in the meta-analysis. The data were synthesized using a random-effects multilevel meta-analysis, which revealed a significant large positive association between ACEs score and TBI occurrence, = 0.31, 95% confidence interval [0.13, 0.49], < 0.001. Moderator analyses did not yield significant results. The current findings demonstrate that individuals who reported a higher ACEs score were more likely to have reported sustaining a TBI, highlighting a need for trauma-informed efforts to prevent TBI and its adverse effects.
Joseph Denk AL, Iverson GL, Terry DP
… +1 more, Valera EM
J Neurotrauma
· 2025 Nov · PMID 40892435
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Individuals who experience intimate partner violence (IPV) sometimes self-report balance and vestibular problems; however, objectively measured balance has rarely been investigated in this population. Given the risk for...Individuals who experience intimate partner violence (IPV) sometimes self-report balance and vestibular problems; however, objectively measured balance has rarely been investigated in this population. Given the risk for persistent physical, neurocognitive, and psychological effects of brain injury (BI) in women who experience IPV, the present study evaluated the association between mild IPV-BIs, objective balance, and self-reported vestibular symptoms in women with at least one instance of physical IPV ( = 144). IPV-BIs and accident-related BIs were assessed using the Ohio State University traumatic BI (TBI) identification method and the Brain Injury Severity Assessment Interview. Psychological symptoms were measured with the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Posttraumatic Stress Disorder Checklist for DSM-5. Vestibular symptoms were measured with the Neurobehavioral Symptom Inventory (NSI). Static balance and postural sway were measured with the Sway Medical System Balance Test, for which lower scores reflect worse balance. Hierarchical regression analyses revealed that having a greater number of mild IPV-related BIs was related to (1) lower objectively measured balance scores (adjusting for age, accident-related BIs, and moderate-severe IPV-BIs) and (2) worse self-reported vestibular symptoms on the NSI (adjusting for age, accident-BIs, moderate-severe IPV-BIs, and symptoms of depression, anxiety, and traumatic stress). Worse self-reported vestibular symptoms were also related to lower balance scores. Results from the present study add to the literature describing the complex health problems experienced by women who experience IPV and IPV-related brain injuries. Future research could include in-person evaluations designed to identify treatable vestibular symptoms and problems.
Traumatic brain injury (TBI) disrupts the intestinal barrier, linking brain trauma to systemic inflammation and secondary complications. This study investigated the role of gut microbiota and its metabolites in intestina...Traumatic brain injury (TBI) disrupts the intestinal barrier, linking brain trauma to systemic inflammation and secondary complications. This study investigated the role of gut microbiota and its metabolites in intestinal barrier dysfunction following TBI, using a controlled cortical impact mouse model. TBI-induced gut dysbiosis was characterized by reduced microbial diversity and a loss of butyrate-producing bacteria, which led to decreased levels of short-chain fatty acids (SCFAs), particularly butyric acid. This disruption compromised the interleukin-22/regenerating islet-derived protein 3 (IL-22/Reg3) signaling pathway, which is essential for maintaining gut barrier integrity. Supplementation with restored butyric acid production, enhanced IL-22/Reg3 expression, and alleviated TBI-induced intestinal permeability. These findings identify the SCFA/IL-22/Reg3 axis as a key mediator of gut barrier homeostasis after TBI and highlight the potential therapeutic role of butyrate-producing probiotics in managing TBI-associated intestinal complications.
Smith CA, Bögli SY, Placek M
… +25 more, Cabeleira M, White D, Daubney E, Young A, Beqiri E, Kayani R, O'Donnell R, Pathan N, Watson S, Maw A, Garnett M, Krishnan Kanthimathinathan H, Bangalore H, Sundararajan S, Subramanian G, Raffaj D, Lampariello S, Sarfatti A, Mayer A, Ross O, Czosnyka M, Hutchinson PJ, Smielewski P, Agrawal S, STARSHIP Study Team
J Neurotrauma
· 2025 Nov · PMID 40844417
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Cerebral autoregulation (CA) plays a critical role in maintaining cerebral blood flow (CBF) amid fluctuations in systemic blood pressure, with dysfunction increasing vulnerability to secondary brain injury, particularly...Cerebral autoregulation (CA) plays a critical role in maintaining cerebral blood flow (CBF) amid fluctuations in systemic blood pressure, with dysfunction increasing vulnerability to secondary brain injury, particularly after traumatic brain injury (TBI). While extensively studied in adults, CA dynamics in pediatric TBI (pTBI) remain relatively unexplored. Studying Trends in AutoRegulation in Severe Head Injury in Pediatrics (STARSHIP), the first multicenter, prospective study on CA in pTBI, investigates the pressure reactivity index (PRx) and its association with outcomes. PRx, calculated as the Pearson's correlation between mean arterial pressure and intracranial pressure, provides insights into the patient's CA status. In this article, STARSHIP Part 2 characterizes PRx disturbances using dose metrics that take the magnitude of PRx disturbance, and the time in which the patient experiences this derangement, into consideration. We calculated the dose (overall and hourly) and percentage time spent with a PRx above thresholds 0-0.4 in 135 children with TBI. Associations with outcome were explored via summary metrics and over time, using uni- and multivariable, and ordinal regression with propensity score matching, correcting for known outcome predictors. Patients with poor outcomes exhibited higher PRx dose and percentage time above threshold, even after adjusting for clinical predictors. Time trend analyses highlighted elevated PRx metrics in poor outcome groups during the first-week post-injury. Duration of impaired pressure reactivity, as denoted by the percentage time a patient spent with a PRx >0, is robustly and independently associated with dichotomized outcome at 12 months post-ictus. Our results highlight the predictive strength of PRx metrics, with percentage time above a threshold of 0 emerging as the most robust indicator of 12-month outcome. This work supports further investigation into the feasibility and impact of interventions guided by real-time CA monitoring in severe pTBI.
Traumatic brain injury (TBI) leads to significant public health concerns due to cognitive decline and increased risks of neurological conditions like Alzheimer's disease and chronic traumatic encephalopathy. Preclinical...Traumatic brain injury (TBI) leads to significant public health concerns due to cognitive decline and increased risks of neurological conditions like Alzheimer's disease and chronic traumatic encephalopathy. Preclinical models are essential for exploring how mild TBI leads to neuronal dysfunction and neurodegeneration. Using a mouse model, we applied repetitive, mild, side-alternating impacts to induce rapid head rotational acceleration-deceleration. A novel odor-based learning and memory task was developed to address TBI-related vision impairments. Our findings revealed that this side-impact model specifically affects the hippocampus, evidenced by activated CD68+ microglia appearing in the dentate gyrus, stratum lacunosum-moleculare, and corpus callosum. Importantly, no olfactory dysfunction was observed. However, injured mice exhibited learning and memory deficits in an olfaction-based task. These results suggest that repetitive mild TBI damages hippocampal regions, leading to cognitive dysfunction characterized by impaired learning and memory, as demonstrated by this novel behavioral method.
Ecological momentary assessment (EMA) is a data collection method involving real-time, repeated sampling of behavior in the natural environment. Having gained traction over the years in areas of psychology and public hea...Ecological momentary assessment (EMA) is a data collection method involving real-time, repeated sampling of behavior in the natural environment. Having gained traction over the years in areas of psychology and public health, EMA's application in individuals with acquired brain injuries (ABIs) is now beginning to be explored. Our review aims to introduce ABI researchers to EMA and the work conducted to date, specifically in traumatic brain injury and stroke cohorts. First, we outline the essential methodological components used, including sampling schemes, measures, and statistical analyses. Second, we synthesize diverse applications of EMA into five overarching themes, encompassing: (a) contextual-temporal relationships between symptoms, (b) intraindividual variability, (c) individual differences in daily life experiences, (d) comparison with traditional measures, and (e) combined use with wearables. Next, we discuss challenges faced by the field around the feasibility and optimization of EMA protocols, as well as emerging applications in clinical assessment, intervention, cognitive assessment, and brain-behavior investigations. Our review highlights EMA's potential for ABI, encouraging wider adoption for enhanced patient care and research advancement.
McNamara CR, Berger RP, Luther JF
… +8 more, Bell MJ, Buttram SDW, Subramanian S, Carpenter JL, Narayanan S, Wisniewski SR, Kochanek PM, Miller Ferguson N
J Neurotrauma
· 2025 Nov · PMID 40803679
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Abusive head trauma (AHT) is a leading cause of death in infants and toddlers. The objective of this study was to conduct an age-stratified comparison between children with AHT and accidental Traumatic brain injury TBI (...Abusive head trauma (AHT) is a leading cause of death in infants and toddlers. The objective of this study was to conduct an age-stratified comparison between children with AHT and accidental Traumatic brain injury TBI (aTBI) in the Approaches and Decisions in Acute Pediatric Traumatic Brain Injury (ADAPT) data. Children with severe TBI and an intracranial pressure monitor placed at a study site in the United States were enrolled from February 1, 2014, to September 31, 2017, and subjects <5 years of age and admitted to a US site were selected for analysis. Subjects were stratified by mechanism ('definite' or 'probable' concern for AHT classified as AHT; 'possible' or 'no' concern for AHT as aTBI) and age (<1 year, 1-2.9-years-, 3-4.9-years). Clinical data including epidemiological, clinical events, and imaging that occurred before monitor placement were compared. Of the 313 subjects (n = 111 AHT), apnea, seizures, and bilateral fixed pupils were more frequently observed in AHT (35.1% vs. 21.8%, = 0.01; 43.2% vs. 20.8, < 0.001; 31.5% vs. 15.8%, = 0.008). Subdural hemorrhages, midline shift, and ischemia were more frequently observed in AHT (96.4% vs. 73.1%, < 0.001; 54.1% vs. 35.0%, = 0.001; 40.9% vs. 12.2%, < 0.001) while contusion, subarachnoid hemorrhage and diffuse axonal injury were less frequently observed (20.2% vs. 49.7%; 38.5% vs. 58.4%; 3.7% vs. 20.8%, all < 0.001). Among the patients <1 year-old, there was no difference in apnea and seizures between AHT and aTBI (40.6% vs. 34.3%, = 0.53; 44.9% vs. 40.0%, = 0.63) while ischemia was more commonly observed in AHT (47.1% vs. 20.0%, < 0.001). AHT subjects exhibited unique clinical characteristics and radiological findings compared to aTBI, even after this age-stratified comparison. Further study is needed on the effects of both guidelines-based and novel therapies for this vulnerable and unique patient population.
Headache is the most common pain complaint following mild traumatic brain injury. Roughly half of those with persistent post-traumatic headache (PPTH) also report neck pain, which is associated with greater severity and...Headache is the most common pain complaint following mild traumatic brain injury. Roughly half of those with persistent post-traumatic headache (PPTH) also report neck pain, which is associated with greater severity and functional impact of headache. This observational cohort study aimed to identify biological phenotypes to help inform mechanism-based approaches in the management of PPTH with co-occurring neck pain. Thirty-three military veterans [mean (standard deviation) = 37 ± 16 years, 29 males] with PPTH completed a clinical assessment, quantitative sensory testing, and magnetic resonance imaging of the brain and cervical spine. Multidimensional phenotyping was performed using a Random Forest analysis and Partitioning Around Medoids clustering of input features from three biological domains: (1) resting state functional connectivity (rsFC) of the periaqueductal gray (PAG), (2) quality and size of cervical muscles, and (3) mechanical pain sensitivity and modulation. Two subgroups were distinguished by biological features that included forehead pressure pain threshold and rsFC between the PAG and selected nodes within the default mode, salience, and sensorimotor networks. Compared to the High Pain Coping group, the Low Pain Coping group exhibited higher pain-related anxiety ( = 0.009), higher pain catastrophizing ( = 0.004), lower pain self-efficacy ( = 0.010), and greater headache-related disability ( = 0.012). Although limited by a modest sample size, findings suggest that greater functional connectivity of pain modulation networks involving the PAG combined with impairments in craniofacial pain sensitivity, but not cervical muscle health, distinguish a clinically important subgroup of individuals with PPTH who are less able to cope with pain and more severely impacted by headache.