High-fat diet consumption negatively influences closed-head traumatic brain injury in a pediatric rodent model.

Traumatic brain injury (TBI) is one of the most common causes of emergency room visits in children, and it is a leading cause of death in juveniles in the United States. Similarly, a high proportion of this population consumes diets that are high in saturated fats, and millions of children are overweight or obese. The goal of the present study was to assess the relationship between diet and TBI on cognitive and cerebrovascular outcomes in juvenile rats. In the current study, groups of juvenile male Long Evans rats were subjected to either mild TBI via the Closed-Head Injury Model of Engineered Rotational Acceleration (CHIMERA) or underwent sham procedures. The animals were provided with either a combination of high-fat diet and a mixture of high-fructose corn syrup (HFD/HFCS) or a standard chow diet (CH) for 9 days prior to injury. Prior to injury, the animals were trained on the Morris water maze for three consecutive days, and they underwent a post-injury trial on the day of the injury. Immediately after TBI, the animals' righting reflexes were tested. Four days post-injury, the animals were euthanized, and brain samples and blood plasma were collected for qRT-PCR, immunohistochemistry, and triglyceride assays. Additional subsets of animals were used to investigate cerebrovascular perfusion using Laser Speckle and perform immunohistochemistry for endothelial cell marker RECA. Following TBI, the righting reflex was significantly increased in TBI rats, irrespective of diet. The TBI worsened the rats' performance in the post-injury trial of the water maze at 3 h, p(injury) < 0.05, but not at 4 days post-injury. Reduced cerebrovascular blood flow using Laser Speckle was demonstrated in the cerebellum, p(injury) < 0.05, but not foci of the cerebral cortices or superior sagittal sinus. Immunoreactive staining for RECA in the cortex and corpus callosum was significantly reduced in HFD/HFCS TBI rats, p < 0.05. qRT-PCR showed significant increases in APOE, CREB1, FCGR2B, IL1B, and IL6, particularly in the hippocampus. The results from this study offer robust evidence that HFD/HFCS negatively influences TBI outcomes with respect to cognition and cerebrovascular perfusion of relevant brain regions in the juvenile rat.

ZL006 mitigates anxiety-like behaviors induced by closed head injury through modulation of the neural circuit from the medial prefrontal cortex to amygdala.

Closed head injury is a prevalent form of traumatic brain injury with poorly understood effects on cortical neural circuits. Given the emotional and behavioral impairments linked to closed head injury, it is vital to uncover brain functional deficits and their driving mechanisms. In this study, we employed a robust viral tracing technique to identify the alteration of the neural pathway connecting the medial prefrontal cortex to the basolateral amygdala, and we observed the disruptions in neuronal projections between the medial prefrontal cortex and the basolateral amygdala following closed head injury. Remarkably, our results highlight that ZL006, an inhibitor targeting PSD-95/nNOS interaction, stands out for its ability to selectively reverse these aberrations. Specifically, ZL006 effectively mitigates the disruptions in neuronal projections from the medial prefrontal cortex to basolateral amygdala induced by closed head injury. Furthermore, using chemogenetic approaches, we elucidate that activating the medial prefrontal cortex projections to the basolateral amygdala circuit produces anxiolytic effects, aligning with the therapeutic potential of ZL006. Additionally, ZL006 administration effectively mitigates astrocyte activation, leading to the restoration of medial prefrontal cortex glutamatergic neuron activity. Moreover, in the context of attenuating anxiety-like behaviors through ZL006 treatment, we observe a reduction in closed head injury-induced astrocyte engulfment, which may correlate with the observed decrease in dendritic spine density of medial prefrontal cortex glutamatergic neurons.

Decompressive craniectomy surgery in a dog with intracranial extradural hematoma following blunt force trauma.

A young miniature poodle was presented following blunt force trauma to the head. The dog initially responded well to medical management before developing clinical signs associated with increased intracranial pressure 48 h post-injury that became refractory to hyperosmolar therapy. A computed tomography scan obtained 76 h post-injury showed a short, oblique, non-displaced, complete fissure in the right temporal bone and a second short, oblique, non-displaced, complete fissure in the ventral aspect of the temporal bone. A biconvex, moderately hyperattenuating, space-occupying temporoparietal lesion was visualized immediately adjacent to the area of the temporal fractures. These findings were consistent with a diagnosis of intracranial extradural hematoma. Decompressive craniectomy successfully evacuated the extradural hematoma to alleviate increased intracranial pressure. The dog's neurologic function recovered quickly postoperatively. At follow-up physical examinations at 14 and 437 d, excellent return to function was noted. Key clinical message: This report describes the diagnosis and surgical management of an intracranial extradural hematoma in a dog with increased intracranial pressure refractory to medical management. Furthermore, this report describes the diagnostic imaging findings used to diagnose this particular form of primary brain injury.

Chirurgie de craniectomie décompressive chez un chien présentant un hématome extradural intracrânien à la suite d'un traumatisme contondant. Un jeune caniche miniature a été présenté à la suite d'un traumatisme contondant à la tête. Le chien a initialement bien répondu à la prise en charge médicale avant de développer des signes cliniques associés à une augmentation de la pression intracrânienne 48 heures après la blessure, qui sont devenus réfractaires au traitement hyperosmolaire. Une tomodensitométrie obtenue 76 heures après la blessure a montré une fissure complète courte, oblique, non déplacée dans l'os temporal droit et une deuxième fissure complète courte, oblique, non déplacée dans la face ventrale de l'os temporal. Une lésion temporo-pariétale biconvexe, modérément hyperatténuée et occupant de l'espace a été visualisée immédiatement à côté de la zone des fractures temporales. Ces résultats concordaient avec un diagnostic d'hématome extradural intracrânien. La craniectomie décompressive a réussi à évacuer l'hématome extradural pour atténuer l'augmentation de la pression intracrânienne. La fonction neurologique du chien s'est rétablie rapidement après l'opération. Lors des examens physiques de suivi à 14 et 437 jours, un excellent retour au fonctionnement a été noté.Message clinique clé:Ce rapport décrit le diagnostic et la prise en charge chirurgicale d'un hématome extradural intracrânien chez un chien présentant une augmentation de la pression intracrânienne réfractaire à la prise en charge médicale. En outre, ce rapport décrit les résultats de l'imagerie diagnostique utilisée pour diagnostiquer cette forme particulière de lésion cérébrale primaire.(Traduit par Dr Serge Messier).

Closed head injury combined with orbital blowout fracture and displacement of the eyeball into the maxillary sinus in a 14-year-old boy: a case report.

BACKGROUND: Trauma-induced orbital blowout fracture (OBF) with eyeball displacement into the maxillary sinus is rare. CASE PRESENTATION: We present the case of a 14-year-old with a closed head injury, OBF, and displacement of the eyeball into the maxillary sinus following a car accident. A prompt transconjunctival access surgery was performed for eyeball repositioning and orbital reconstruction in a single session, mitigating anaesthesia-related risks associated with multiple surgeries. At the 12-month follow-up, his visual acuity was 20/200. Despite limited eye movement and optic nerve atrophy, overall satisfaction with the ocular appearance was achieved. CONCLUSIONS: This report offers novel insights into the mechanisms of OBF occurrence and the development of postoperative complications.

Effects of Mild Closed-Head Injury and Subanesthetic Ketamine Infusion on Microglia, Axonal Injury, and Synaptic Density in Sprague-Dawley Rats.

Mild traumatic brain injury (mTBI) affects millions of people in the U.S. Approximately 20-30% of those individuals develop adverse symptoms lasting at least 3 months. In a rat mTBI study, the closed-head impact model of engineered rotational acceleration (CHIMERA) produced significant axonal injury in the optic tract (OT), indicating white-matter damage. Because retinal ganglion cells project to the lateral geniculate nucleus (LGN) in the thalamus through the OT, we hypothesized that synaptic density may be reduced in the LGN of rats following CHIMERA injury. A modified SEQUIN (synaptic evaluation and quantification by imaging nanostructure) method, combined with immunofluorescent double-labeling of pre-synaptic (synapsin) and post-synaptic (PSD-95) markers, was used to quantify synaptic density in the LGN. Microglial activation at the CHIMERA injury site was determined using Iba-1 immunohistochemistry. Additionally, the effects of ketamine, a potential neuroprotective drug, were evaluated in CHIMERA-induced mTBI. A single-session repetitive (ssr-) CHIMERA (3 impacts, 1.5 joule/impact) produced mild effects on microglial activation at the injury site, which was significantly enhanced by post-injury intravenous ketamine (10 mg/kg) infusion. However, ssr-CHIMERA did not alter synaptic density in the LGN, although ketamine produced a trend of reduction in synaptic density at post-injury day 4. Further research is necessary to characterize the effects of ssr-CHIMERA and subanesthetic doses of intravenous ketamine on different brain regions and multiple time points post-injury. The current study demonstrates the utility of the ssr-CHIMERA as a rodent model of mTBI, which researchers can use to identify biological mechanisms of mTBI and to develop improved treatment strategies for individuals suffering from head trauma.

Distinctive patterns of sequential platelet counts following blunt traumatic brain injury predict outcomes.

OBJECTIVE: To determine the role of platelet counts in the context of the decision to treat patients with non-compounded, non-surgically-treated blunt traumatic brain injury (NCNS-bTBI) with anticoagulants/antiaggregants. METHODS: A retrospective analysis of 141 anticoagulants/antiaggregants-naïve patients with NCNS-bTBI. Changes in PT-INR and prolonged aPTT were examined and correlated with Marshall and Rotterdam scores, clinical and neuroradiological outcomes. RESULTS: Three groups of platelet counts were identified. Group 1 (83% of patients) had normal platelet counts (150,000-450,000 platelets/mm3) from admission to discharge. Group 2 (13%) developed transient thrombocytopenia (<150,000 platelets/mm3) 2-3 days post-trauma. Group 3 (4%) developed extreme thrombocytosis > 1,000,000/mm3 platelets 6-9 days post-trauma. Neither acute coagulopathy of trauma nor progressive hemorrhagic insults followed NCNS-bTBI. Moreover, while patients with thrombocytosis/extreme thrombocytosis presented with a worse Glasgow coma score (GCS) on admission (8.8 ± 2.9 vs. 13 ± 2, p < 0.01) and had longer hospitalization (13.5 ± 10.4 vs. 4.5 ± 2.1 days), their improvement at discharge was the highest (delta GCS, 4 ± 2.8 vs. 1.2 ± 2.1, p = 0.05). Traumatic subarachnoid hemorrhage was associated with isolated thrombocytosis and 'best improvement.' No thromboembolic or hemorrhagic complications occurred. CONCLUSION: NCNS-bTBI, thrombocytosis was correlated with better outcomes and was not associated with an increased risk for developing thromboembolism or hemorrhage, precluding the immediate need for any additional antiaggregates.

Blunt Head Injury in the Elderly: Analysis of the NEXUS II Injury Cohort.

BACKGROUND: Changes with aging make older patients vulnerable to blunt head trauma and alter the potential for injury and the injury patterns seen among this expanding cohort. High-quality care requires a clear understanding of the factors associated with blunt head injuries in the elderly. Our objective was to develop a detailed assessment of the injury mechanisms, presentations, injury patterns, and outcomes among older blunt head trauma patients. METHODS: We conducted a planned secondary analysis of patients aged 65 or greater who were enrolled in the National Emergency X-Radiography Utilization Study (NEXUS) Head Computed Tomography validation study. We performed a detailed assessment of the demographics, mechanisms, presentations, injuries, interventions, and outcomes among older patients. RESULTS: We identified 3,659 patients aged 65 years or greater, among the 11,770 patients enrolled in the NEXUS validation study. Of these older patients, 325 (8.9%) sustained significant injuries, as compared with significant injuries in 442 (5.4%) of the 8,111 younger patients. Older females (1,900; 51.9%) outnumbered older males (1,753; 47.9%), and occult presentations (exhibiting no high-risk clinical criteria beyond age) occurred in 48 (14.8%; 95% confidence interval (CI) 11.1 to 19.1) patients with significant injuries. Subdural hematomas (377 discreet lesions in 299 patients) and subarachnoid hemorrhages (333 discreet instances in 256 patients) were the most frequent types of injuries occurring in our elderly population. A ground-level fall was the most frequent mechanism of injury among all patients (2,211; 69.6%), those sustaining significant injuries (180; 55.7%), and those who died of their injuries (37; 46.3%), but mortality rates were highest among patients experiencing a fall from a ladder (11.8%; 4 deaths among 34 cases [95% CI 3.3% to 27.5%]) and automobile versus pedestrian events (10.7%; 16 deaths among 149 cases [95% CI 6.3% to 16.9%]). Among older patients who required neurosurgical intervention for their injuries, only 16.4% (95% CI 11.1% to 22.9%) were able to return home, 32.1% (95% CI 25.1% to 39.8%) required extended facility care, and 41.8% (95% CI 34.2% to 49.7%) died from their injuries. CONCLUSIONS: Older blunt head injury patients are at high risk of sustaining serious intracranial injuries even with low-risk mechanisms of injury, such as ground-level falls. Clinical evaluation is unreliable and frequently fails to identify patients with significant injuries. Outcomes, particularly after intervention, can be poor, with high rates of long-term disability and mortality.

Incomplete accumulation of perilesional reactive astrocytes exacerbates wound healing after closed-head injury by increasing inflammation and BBB disruption.

Wound healing after closed-head injury is a significant medical issue. However, conventional models of focal traumatic brain injury, such as fluid percussion injury and controlled cortical impact, employ mechanical impacts on the exposed cerebral cortex after craniotomy. These animal models are inappropriate for studying gliosis, as craniotomy itself induces gliosis. To address this, we developed a closed-head injury model and named "photo injury", which employs intense light illumination through a thinned-skull cranial window. Our prior work demonstrated that the gliosis of focal cerebral lesion after the photo injury does not encompass artificial gliosis and comprises two distinct reactive astrocyte subpopulations. The reactive astrocytes accumulated in the perilesional recovery area actively proliferate and express Nestin, a neural stem cell marker, while those in distal regions do not exhibit these traits. The present study investigated the role of perilesional reactive astrocytes (PRAs) in wound healing using the ablation of reactive astrocytes by the conditional knockout of Stat3. The extensive and non-selective ablation of reactive astrocytes in Nestin-Cre:Stat3f/f mice resulted in an exacerbation of injury, marked by increased inflammation and BBB disruption. On the other hand, GFAP-CreERT2:Stat3f/f mice exhibited the partial and selective ablation of the PRAs, while their exacerbation of injury was at the same extent as in Nestin-Cre:Stat3f/f mice. The comparison of these two mouse strains indicates that the PRAs are an essential astrocyte component for wound healing after closed-head injury, and their anti-inflammatory and regenerative functions are significantly affected even by incomplete accumulation. In addition, the reporter gene expression in the PRAs by GFAP-CreERT2 indicated a substantial elimination of these cells and an absence of differentiation into other cell types, despite Nestin expression, after wound healing. Thus, the accumulation and subsequent elimination of PRA are proposed as promising diagnostic and therapeutic avenues to bolster wound healing after closed-head injury.

Murine Traumatic Brain Injury Model Comparison: Closed Head Injury Versus Controlled Cortical Impact.

INTRODUCTION: Various murine models have been utilized to study TBI, including closed head injury (CHI) and controlled cortical impact (CCI), without direct comparison. The aim of our study was to evaluate these models to determine differences in neurological and behavioral outcomes postinjury. METHODS: Male C57B/6 mice (9-10 wk) were separated into six groups including: untouched, sham craniotomy (4 mm), CCI 0.9 mm depth of impact, CCI 1.6 mm, CCI 2.2 mm, and CHI. CCI was performed using a 3 mm impact tip at a velocity of 5 m/s, dwell time of 250 ms, and depth as noted above. CHI was completed with a centered 400 g weight drop from 1 cm height. Mice were survived to 14-d (n = 5 per group) and 30-d (n = 5 per group) respectively for histological analysis of p-tau within the hippocampus. These mice underwent Morris Water Maze memory testing and Rotarod motor testing. Serum was collected from a separate cohort of mice (n = 5 per group) including untouched, isoflurane only, CCI 1.6 mm, CHI at 1, 4, 6, and 24 h for analysis of neuron specific enolase and glial fibrillary acidic protein (GFAP) via ELISA. Laser speckle contrast imaging was analyzed prior to and after impact in the CHI and CCI 1.6 mm groups. RESULTS: There were no significant differences in Morris Water Maze or Rotarod testing times between groups at 14- or 30-d. P-tau was significantly elevated in all groups except CCI 1.6 mm contralateral and CCI 2.2 mm ipsilateral compared to untouched mice at 30-d. P-tau was also significantly elevated in the CHI group at 30 d compared to CCI 1.6 mm contralateral and CCI 2.2 mm on both sides. GFAP was significantly increased in mice undergoing CHI (9959 ± 91 pg/mL) compared to CCI (2299 ± 1288 pg/mL), isoflurane only (133 ± 75 pg/mL), and sham (86 ± 58 pg/mL) at 1-h post TBI (P < 0.0001). There were no differences in serum neuron specific enolase levels between groups. Laser doppler imaging demonstrated similar decreases in cerebral blood flow between CHI and CCI; however, CCI mice had a reduction in blood flow with craniotomy only that did not significantly decrease further with impact. CONCLUSIONS: Based on our findings, CHI leads to increased serum GFAP levels and increased p-tau within the hippocampus at 30-d postinjury. While CCI allows the comparison of one cerebral hemisphere to the other, CHI may be a better model of TBI as it requires less technical expertise and has similar neurological outcomes in these murine models.

Glial cells react to closed head injury in a distinct and spatiotemporally orchestrated manner.

Traumatic brain injury (TBI) is a leading cause of mortality and disability worldwide. Acute neuroinflammation is a prominent reaction after TBI and is mostly initiated by brain-resident glial cells such as microglia, NG2-glia and astrocytes. The magnitude of this reaction paves the way for long-lasting consequences such as chronic neurological pathologies, for which therapeutic options remain limited. The neuroinflammatory response to TBI is mostly studied with craniotomy-based animal models that are very robust but also rather artificial. Here, we aimed to analyze the reaction of glial cells in a highly translational but variable closed head injury (CHI) model and were able to correlate the severity of the trauma to the degree of glial response. Furthermore, we could show that the different glial cell types react in a temporally and spatially orchestrated manner in terms of morphological changes, proliferation, and cell numbers in the first 15 days after the lesion. Interestingly, NG2-glia, the only proliferating cells in the healthy brain parenchyma, divided at a rate that was correlated with the size of the injury. Our findings describe the previously uncharacterized posttraumatic response of the major brain glial cell types in CHI in order to gain a detailed understanding of the course of neuroinflammatory events; such knowledge may open novel avenues for future therapeutic approaches in TBI.

Photobiomodulation therapy alleviates repeated closed head injury-induced anxiety-like behaviors.

Repeated closed head injury (rCHI) is one of the most common brain injuries. Although extensive studies have focused on how to treat rCHI-induced brain injury and reduce the possibility of developing memory deficits, the prevention of rCHI-induced anxiety has received little research attention. The current study was designed to assess the effects of photobiomodulation (PBM) therapy in preventing anxiety following rCHI. The rCHI disease model was constructed by administering three repeated closed-head injuries within an interval 5 days. 2-min daily PBM therapy using an 808 nm continuous wave laser at 350 mW/cm2 on the scalp was implemented for 20 days. We found that PBM significantly ameliorated rCHII-induced anxiety-like behaviors, neuronal apoptosis, neuronal injury, promotes astrocyte/microglial polarization to anti-inflammatory phenotype, preserves mitochondrial fusion-related protein MFN2, attenuates the elevated mitochondrial fission-related protein DRP1, and mitigates neuronal senescence. We concluded that PBM therapy possesses great potential in preventing anxiety following rCHI.

Adolescent Trauma Patients With Isolated Head Trauma and Glasgow Coma Scale 6-8: Routine Intubation?

BACKGROUND: Recent evidence suggests that routine intubation upon arrival for adults with isolated head trauma and a depressed Glasgow Coma Scale (GCS) score is associated with increased risk of morbidity and mortality. Whether these outcomes are similar within an adolescent trauma population has not been previously investigated. We hypothesized intubation upon arrival for adolescent trauma patients with isolated head trauma to be associated with a higher risk of death and prolonged length of stay (LOS). METHODS: The 2017-2019 TQIP was queried for adolescents (age 12-16) presenting after isolated blunt head trauma (abbreviated injury scale [AIS] <1 spine/chest/abdomen/upper-extremity/lower-extremity) and GCS 6-8 on arrival. Transferred patients, dead-on-arrival, and those undergoing emergent operation from the emergency department were excluded. Patients intubated within one-hour were compared to patients not intubated within one-hour. A multivariable logistic regression analysis was performed adjusting for age, sex, GCS, and AIS-grade for the head. RESULTS: From 141 patients, 73 (51.8%) were intubated upon arrival. Intubated patients had a low complication rate (5.6%). Intubated and non-intubated patients had a similar rate and mortality risk (6.8% vs 1.5%, P = .11) (OR 1.84, CI .08-43.69, P = .71) and median length of stay (LOS) (2 days vs 2 days, P = .13). DISCUSSION: Unlike adult patients, adolescents with isolated head trauma and a depressed GCS have similar outcomes if they are intubated upon arrival. Utilizing initial GCS score to determine which adolescent trauma patients with isolated head trauma should be intubated appears to be a safe practice.

Risk factors for thromboembolic complications in isolated severe head injury.

PURPOSE: Patients with traumatic brain injury (TBI) are at high risk for venous thromboembolism (VTE). The aim of the present study is to identify factors independently associated with VTE events. Specifically, we hypothesized that the mechanism of penetrating head trauma might be an independent factor associated with increased VTE events when compared with blunt head trauma. METHODS: The ACS-TQIP database (2013-2019) was queried for all patients with isolated severe head injuries (AIS 3-5) who received VTE prophylaxis with either unfractionated heparin or low-molecular-weight heparin. Transfers, patients who died within 72 h and those with a hospital length of stay < 48 h were excluded. Multivariable analysis was used as the primary analysis to identify independent risk factors for VTE in isolated severe TBI. RESULTS: A total of 75,570 patients were included in the study, 71,593 (94.7%) with blunt and 3977 (5.3%) with penetrating isolated TBI. Penetrating trauma mechanism (OR 1.49, CI 95% 1.26-1.77), increasing age (age 16-45: reference; age > 45-65: OR 1.65, CI 95% 1.48-1.85; age > 65-75: OR 1.71, CI 95% 1.45-2.02; age > 75: OR 1.73, CI 95% 1.44-2.07), male gender (OR 1.53, CI 95% 1.36-1.72), obesity (OR 1.35, CI 95% 1.22-1.51), tachycardia (OR 1.31, CI 95% 1.13-1.51), increasing head AIS (AIS 3: reference; AIS 4: OR 1.52, CI 95% 1.35-1.72; AIS 5: OR 1.76, CI 95% 1.54-2.01), associated moderate injuries (AIS = 2) of the abdomen (OR 1.31, CI 95% 1.04-1.66), spine (OR 1.35, CI 95% 1.19-1.53), upper extremity (OR 1.16, CI 95% 1.02-1.31), lower extremity (OR 1.46, CI 95% 1.26-1.68), craniectomy/craniotomy or ICP monitoring (OR 2.96, CI 95% 2.65-3.31) and pre-existing hypertension (OR 1.18, CI 95% 1.05-1.32) were identified as independent risk factors for VTE complications in isolated severe head injury. Increasing GCS (OR 0.93, CI 95% 0.92-0.94), early VTE prophylaxis (OR 0.48, CI 95% 0.39-0.60) and LMWH compared to heparin (OR 0.74, CI 95% 0.68-0.82) were identified as protective factors for VTE complications. CONCLUSION: The identified factors independently associated with VTE events in isolated severe TBI need to be considered in VTE prevention measures. In penetrating TBI, an even more aggressive VTE prophylaxis management may be justified as compared to that in blunt.

Repeated mild traumatic brain injury causes sex-specific increases in cell proliferation and inflammation in juvenile rats.

Childhood represents a period of significant growth and maturation for the brain, and is also associated with a heightened risk for mild traumatic brain injuries (mTBI). There is also concern that repeated-mTBI (r-mTBI) may have a long-term impact on developmental trajectories. Using an awake closed head injury (ACHI) model, that uses rapid head acceleration to induce a mTBI, we investigated the acute effects of repeated-mTBI (r-mTBI) on neurological function and cellular proliferation in juvenile male and female Long-Evans rats. We found that r-mTBI did not lead to cumulative neurological deficits with the model. R-mTBI animals exhibited an increase in BrdU + (bromodeoxyuridine positive) cells in the dentate gyrus (DG), and that this increase was more robust in male animals. This increase was not sustained, and cell proliferation returning to normal by PID3. A greater increase in BrdU + cells was observed in the dorsal DG in both male and female r-mTBI animals at PID1. Using Ki-67 expression as an endogenous marker of cellular proliferation, a robust proliferative response following r-mTBI was observed in male animals at PID1 that persisted until PID3, and was not constrained to the DG alone. Triple labeling experiments (Iba1+, GFAP+, Brdu+) revealed that a high proportion of these proliferating cells were microglia/macrophages, indicating there was a heightened inflammatory response. Overall, these findings suggest that rapid head acceleration with the ACHI model produces an mTBI, but that the acute neurological deficits do not increase in severity with repeated administration. R-mTBI transiently increases cellular proliferation in the hippocampus, particularly in male animals, and the pattern of cell proliferation suggests that this represents a neuroinflammatory response that is focused around the mid-brain rather than peripheral cortical regions. These results add to growing literature indicating sex differences in proliferative and inflammatory responses between females and males. Targeting proliferation as a therapeutic avenue may help reduce the short term impact of r-mTBI, but there may be sex-specific considerations.

Management of Acute Injury and Illness in Pediatric Athletes by Athletic Trainers: Compliance With Emergency Medicine and Athletic Trainer Evidence-Based Guidelines.

OBJECTIVE: This study aimed to determine athletic trainer compliance with emergency medicine and athletic training evidence-based guidelines for the on-the-field management of common pediatric sports-related injury and illness. METHODS: A questionnaire was distributed electronically to selected members of the National Athletic Trainer Association. The questionnaire included 10 clinical scenarios describing common sports-related injury/illness (closed head injury, cervical spine injury, blunt chest injury, blunt abdominal injury, ankle injury, knee injury with laceration, heat-related illness). On-the-field management decisions for each scenario were compared with selected emergency medicine and athletic training guidelines. RESULTS: Analysis was performed on 564 completed questionnaires (9% response rate). Responders were compliant with practice guidelines for both emergency medicine and athletic training except for blunt chest trauma with tachycardia, closed head injury with loss of consciousness, closed head injury with repetitive speech, closed head injury with a fall higher than 5 feet, cervical spine injury with paresthesias, and heat-related illness with persistent symptoms. Discrepancies between emergency medicine and athletic training guidelines included closed head injury with repetitive speech, closed head injury and height of fall, closed head injury and unequal pupils, and cervical spine injury with neck pain and paresthesias. CONCLUSIONS: Based on our sample, athletic trainers were compliant with many guidelines supported by both emergency medicine and athletic training. We identified several deficiencies in the availability of evidence-based guidelines and discrepancies between these guidelines and athletic trainer responses. To provide optimal care to pediatric athletes who sustain injury or illness, emergency medicine and athletic training organizations should collaborate to improve these discrepancies.

The epidemiology of crib-related head injuries: A ten-year nationwide analysis.

INTRODUCTION: Falls from cribs resulting in head injury are understudied and poorly characterized. The purpose of this study was to advance current understanding of the prevalence, descriptive characteristics of injury victims, and the types of crib fall-related head injuries (CFHI) using queried patient cases from the National Electronic Injury Surveillance System (NEISS) database. METHODS: Using the US Consumer Product Safety Commission's System NEISS database, we queried all CFHIs among children from over 100 emergency departments (EDs). Patient information regarding age, race, sex, location of the incident, diagnoses, ED disposition, and sequelae were analyzed. The number of CFHI from all US EDs during each year was also collected from the database. RESULTS: There were an estimated 54,799 (95% CI: 30,228-79,369) total visits to EDs for CFHIs between 2012 and 2021, with a decrease in incidence of approximately 20% during the onset of the COVID-19 pandemic (2019: 5616 cases, 2020: 4459 cases). The annual incidence of injuries showed no significant trend over the 10-year study period. An available subset of 1782 cases of head injuries from approximately 100 EDs was analyzed, and 1442 cases were included in final analysis. Injuries were sorted into three primary categories: unspecified closed head injury (e.g., closed head injury, blunt head trauma, or traumatic brain injury), concussion, or open head injury and skull fracture. Unspecified closed head injuries were the most common of all head injuries (95.4%, 1376/1442). Open head injuries (14/1442, 0.97%) and concussions 3.6% (52/1442, 3.6%) were rare. Most injuries involved children under the age of 1 (42.6%) compared to children who were 1, 2, 3, or 4-years old. About a fourth of patients had other diagnoses in addition to their primary injury including scalp/forehead hematomas, emesis, and contusions. Female patients were more likely to present with other diagnoses in addition to their primary head injury (Difference: 12.3%, 95% CI: 9.87%-15.4%, p < .0001). CONCLUSION: Despite minimum rail height requirements set by the Consumer Safety Product Commission (CPSC), head injuries associated with crib falls are prevalent in the United States. However, most injuries were minor with a vast majority of patients being released following examination and treatment.

IL-1R1 signaling in TBI: assessing chronic impacts and neuroinflammatory dynamics in a mouse model of mild closed-head injury.

Neuroinflammation contributes to secondary injury cascades following traumatic brain injury (TBI), with alternating waves of inflammation and resolution. Interleukin-1 (IL-1), a critical neuroinflammatory mediator originating from brain endothelial cells, microglia, astrocytes, and peripheral immune cells, is acutely overexpressed after TBI, propagating secondary injury and tissue damage. IL-1 affects blood-brain barrier permeability, immune cell activation, and neural plasticity. Despite the complexity of cytokine signaling post-TBI, we hypothesize that IL-1 signaling specifically regulates neuroinflammatory response components. Using a closed-head injury (CHI) TBI model, we investigated IL-1's role in the neuroinflammatory cascade with a new global knock-out (gKO) mouse model of the IL-1 receptor (IL-1R1), which efficiently eliminates all IL-1 signaling. We found that IL-1R1 gKO attenuated behavioral impairments 14 weeks post-injury and reduced reactive microglia and astrocyte staining in the neocortex, corpus callosum, and hippocampus. We then examined whether IL-1R1 loss altered acute neuroinflammatory dynamics, measuring gene expression changes in the neocortex at 3, 9, 24, and 72 h post-CHI using the NanoString Neuroinflammatory panel. Of 757 analyzed genes, IL-1R1 signaling showed temporal specificity in neuroinflammatory gene regulation, with major effects at 9 h post-CHI. IL-1R1 signaling specifically affected astrocyte-related genes, selectively upregulating chemokines like Ccl2, Ccl3, and Ccl4, while having limited impact on cytokine regulation, such as Tnfα. This study provides further insight into IL-1R1 function in amplifying the neuroinflammatory cascade following CHI in mice and demonstrates that suppression of IL-1R1 signaling offers long-term protective effects on brain health.

Predictors of Middle Meningeal Artery-Related Vascular Diseases Associated with Blunt Head Trauma.

OBJECTIVE: Traumatic middle meningeal artery (MMA)-middle meningeal vein (MMV) fistula (MMA-MMV fistula) and MMA pseudoaneurysm are the 2 main MMA-related vascular diseases occurring after blunt head trauma. These are rare but known causes of delayed intracranial hemorrhage. This study investigated predictors that may aid in the diagnosis of these diseases. METHODS: In our department, screening digital subtraction angiography (DSA) is performed for patients with blunt head trauma accompanied by intracranial hemorrhage and skull or facial bone fracture. This study included 87 patients who underwent screening DSA without craniotomy from January 2019 to June 2023. The patients' clinical characteristics were retrospectively collected from the database. Statistical analysis was performed to examine the associations of various evaluation items with MMA-related vascular diseases. RESULTS: The first DSA examination revealed 34 MMA-MMV fistulas and 1 MMA pseudoaneurysm. The second follow-up DSA examination revealed 13 MMA-MMV fistulas and four MMA pseudoaneurysms. Temporal/parietal bone fracture (odds ratio, 5.33; P = 0.0005; 95% confidence interval, 1.95-14.60) was significantly associated with MMA-related vascular diseases. Endovascular treatments were performed in 9 patients. All procedures were successfully completed without complications; no delayed bleeding was observed. CONCLUSIONS: Temporal/parietal bone fracture in patients with blunt head trauma is a likely predictor of MMA-related vascular diseases. When initial head computed tomography reveals this pathology, we recommend careful imaging follow-up (e.g., DSA) and treatment as needed, while considering the possibility of MMA-related vascular diseases.

Quantitative Analysis of Ball-Head Impact Exposure in Youth Soccer Players.

Since the implementation of the US Soccer heading guidelines released in 2015, little to no research on ball-head impact exposure in the United States youth soccer population has been conducted. The purpose was to compare ball-head impact exposure across sex and age in youth soccer players over a weekend tournament. Ten male and female games for each age group (Under-12 [U12], U13, and U14) were video recorded at a weekend tournament for a total of 60 games. Ball-head impact exposure for each game was then coded following a review of each recording. Male players were 2.8 times more likely to have ball-head impacts than female players, (p < 0.001) particularly in the U14 age group when compared to the U12 age group (p = 0.012). Overall 92.4% of players experienced 0-1 ball-head impacts per game with the remaining players experiencing 2+ ball-head impacts per game. Ball-head impact exposure levels are low in the youth players. Most youth soccer players do not head the soccer ball during match play and those that did, only headed the ball on average once per game. Overall, the difference in ball-head impact exposure per player was less than 1 between all the groups, which may have no clinical meaning.

Evaluation and Management of Blunt Head Trauma in the Pediatric Clinic.

Head injuries, and specifically blunt head trauma, are common among pediatric patients of all ages. Patients may present to their primary care provider, to urgent care, or to the emergency department after head trauma. Such injuries may occur as a result of a variety of mechanisms, including falls, motor vehicle collisions, or sports injuries. Clinical decision rules exist to help guide the clinician in the initial evaluation of head injury and in determining when head imaging may be indicated. One such guideline that is widely used in the United States is known as the PECARN (Pediatric Emergency Care Applied Research Network) criteria. Pediatricians should also evaluate for the presence of symptoms consistent with concussion that may occur as a result of blunt head trauma and be familiar with the management and sequelae of concussion and head injuries. [Pediatr Ann. 2023;52(8):e279-e281.].