Introduction:Ultra-severe traumatic brain injury (us-TBI), defined as Glasgow Coma Scale score (GCS) of five-three, is associated with high mortality and severe morbidity amongst survivors. However, in selected patients a favourable recovery may still be achieved. Research question:We aimed to characterise what clinical parameters can be used as prognosticators in us-TBI patients. Material and method:A retrospective, single-centre study of 70 us-TBI patients admitted between the years of 2014-2024. Early clinical, and radiological factors were assessed, and patient outcome (Glasgow outcome scale extended- GOSE) was obtained at 3-12 months. Results:The median age was 52.5 years, 21 had GCS five on admission, 23 GCS four and 26 had GCS three. Four patients had on admission bilaterally dilated pupils, 35 patients had unilateral mydriasis, 11 had miotic pupils and 20 had normal pupils. Thirty-one patients (44%) succumbed to their injuries. Median GOSE was three, and nine patients (13%) achieved an excellent outcome (GOSE 7-8) - these patients were younger (median age 26 years) and showed normalised pupil reactivity post-operatively. A favourable outcome (GOSE≥5) was achieved in 19 patients (28%). A combination of GCS 3 and bilaterally dilated pupils was uniformly fatal. Discussion and conclusion:Despite presenting with a low level of consciousness (GCS 3-5) and pupillary abnormalities in 71%, survival was observed in 56% of us-TBI patients, and nine (13%) made an excellent recovery (GOSE 7-8). Improved pupillary reactivity post-intervention may be a positive prognosticator. Our data argue against therapeutic nihilism in us-TBI patient presenting with GCS scores of 5-3.

Secondary brain injury is a common cause of poor outcome after trauma, subarachnoid hemorrhage, and intracerebral hemorrhage, and optimizing treatment requires real-time insight into cerebral metabolism. Cerebral microdialysis (CMD) uniquely provides key related information, yet consensus on its use has not been updated since publication of the consensus statement from the 2014 International Microdialysis Forum. We aimed to assess expert consensus on the use of CMD in critical care and provide contemporary guidance to standardize practice and advance clinical implementation. We conducted a 3-round modified Delphi study with international experts in CMD and neurocritical care. Consensus was defined as ≥ 75

The glymphatic system facilitates cerebrospinal fluid (CSF)–interstitial fluid exchange and plays a key role in solute clearance and neurophysiological homeostasis. While dysfunction of this system has been shown in traumatic brain injury, stroke, meningitis, idiopathic normal pressure hydrocephalus and neurodegenerative diseases, direct measurement of glymphatic transport in humans remains elusive. We propose microGLYMPH as a translational, hypothesis-generating framework that combines established clinical cerebral microdialysis with controlled CSF tracer administration via existing clinical access routes, including an external ventricular drain, cisternal access during surgery, or lumbar intrathecal injection when clinically justified. The aim is to obtain time-resolved regional tracer profiles in microdialysate and to interpret these alongside arousal state, intracranial dynamics, and, where available, complementary imaging, thereby providing an indirect measure of CSF–interstitial exchange kinetics and peripheral tracer appearance. We further define the key design, analytical and practical limitations that must be resolved before the approach can extend beyond exploratory use, notably catheter-adjacent effects, blood–brain barrier disruption, drainage practices, and the intrinsically focal nature of microdialysis. microGLYMPH is therefore intended as a staged roadmap for first-in-human feasibility studies and subsequent hypothesis-driven investigations of neurofluid solute transport after acute brain injury.

Introduction:Traumatic axonal injury (TAI), often caused by rapid rotational forces and high-energy accidents, is common in severe traumatic brain injury (sTBI). The intracranial pressure (ICP) dynamics are often unpredictable, and the need for ICP monitoring remains debated. Research question:What is the incidence of ICP elevation in patients with TAI, and how often is escalated ICP-lowering treatment required? Material and methods:Retrospectively, sTBI patients treated between 2007 and 2022 with TAI lesions at the grey-white matter interface, corpus callosum, deep central structures, and/or brainstem, on magnetic resonance imaging (MRI) were included. Patients with ICP elevation despite baseline management were treated according to the Lund Concept, including beta-blockers, clonidine, and albumin. Decompressive craniectomy (DC) or high-dose barbiturate infusion was reserved for refractory ICP elevation. Results:Thirty-one TAI patients (15 women and 16 men) presented with a median Glasgow Coma Scale motor score of 2 (range 1-6). All patients had TAI lesion in the grey-white interface, 27 patients also in the corpus callosum, and 16 patients had brainstem lesions. Elevated ICP was observed in 16 patients (52 %), of whom 4/16 (25 %) received either DC (n = 2), high-dose barbiturates (n = 1) or both (n = 1). Discussion and conclusion:The risk of increased ICP in TAI patients has been debated. Our present results, showing that 52 % of TAI patients experienced elevated ICP requiring escalated ICP-lowering strategies, argue that ICP monitoring is required in TAI. The impact of increased ICP on outcome following TAI should be explored in future studies.

Introduction:Moderate traumatic brain injury (TBI) is heterogeneous. Admission and injury-related variables may predict outcomes differently, but their relative importance is unclear. Research question:Do admission and injury variables differ in predicting neurosurgical intervention and 30-day mortality in moderate TBI? Material and methods:In a nationwide retrospective cohort study using the Swedish Trauma Registry (SweTrau; 2018-2023), we included adults with moderate TBI (Glasgow Coma Scale 9-13). The primary outcome was neurosurgical intervention; the secondary outcome was 30-day mortality. For each, two multivariable logistic regression models were fitted: an admission model (demographics, comorbidity, physiology) and an injury model (injury severity and intracranial lesions). Discrimination was assessed using the area under the ROC curve (AUC), compared with DeLong's test, and reassessed within age strata (<65 and ≥ 65 years). Results:Among 1761 patients, 198 (11%) underwent neurosurgical intervention and 299 (17%) died within 30 days. The injury model discriminated intervention better than the admission model (AUC 0.84 vs 0.67), in both younger and older patients. For mortality the admission model discriminated better overall (0.84 vs 0.78), but only in older patients: among those <65, injury severity discriminated better (0.88 vs 0.72), whereas among those ≥65 the models were equivalent (0.73 vs 0.71). Increasing age was associated with higher mortality but lower odds of intervention. Discussion and conclusion:In moderate TBI, the information that identifies who needs surgery is not the information that predicts who will survive, and for survival that information itself changes with age. A single severity measure is therefore insufficient.

Isolated severe traumatic brain injury (TBI) is associated with high mortality and long-term morbidity, especially in low- and middle-income countries (LMICs). Despite promising results using pharmacological and non-pharmacological therapies in the experimental setting, no clinical trials have demonstrated robust efficacy. We aimed to investigate the effect of antisecretory factor (Salovum®) on 30-day mortality in adult patients with severe TBI. This was a prospective, double-blind, placebo-controlled phase 2 trial, conducted from September 2017 to February 2022 in a tertiary trauma centre (university hospital) in Cape Town, South Africa (www.clinicaltrials.gov: NCT03339505). The participants were adults with isolated severe TBI (Glasgow Coma Score 6-8), receiving intracranial pressure (ICP) monitoring and neurointensive care. Participants were administered either Salovum® (freeze-dried egg yolk powder enriched with the active compound antisecretory factor) or placebo (freeze dried egg yolk powder) via the nasogastric tubing, dosed according to weight (10-17 g/4 h) and initiated at 32.9 h ± 10.7 h (mean ± standard deviation) post-injury. Study drug or placebo were administered until the ICP monitor was removed or for a maximum of 5 days. The primary outcome of this trial was 30-day mortality and secondary outcome measures were therapy intensity level (TIL) and ICP. One hundred participants aged 18-61 were included, with 49 and 51 patients in the treatment and control groups, respectively. Most patients were male (96%) and the mean age was 33 years. The 30-day mortality rate was 20% in the treatment group and 39% in the control group, yielding a relative risk ratio of 0.52 (confidence interval: 0.271-0.997) and a P-value of 0.040 (chi-square test). TIL and ICP were similar in both groups. No significant adverse events were noted. Antisecretory factor significantly reduced 30-day mortality in severe TBI in an LMIC environment. Further studies investigating the mechanisms by which antisecretory factor act are warranted. The safety, easy administration and marked efficacy of antisecretory factor support exploration in multicentre randomized controlled trials.

Traumatic brain injury (TBI) is commonly associated with white matter injury, leading to persistent symptoms and long-term disability. While advanced age is linked to worse outcome post-TBI, the influence of sex remains highly controversial. The present study aimed to identify age- and sex-dependent differences in white matter pathology during the chronic phase of TBI using the central (midline) fluid percussion injury (cFPI) model. Young (8-12 weeks) and aged (55-78 weeks) male and female mice were subjected to cFPI and end-point analyses were performed at 30 days post-injury (dpi). Histological and immunohistochemical assessments, combined with Western Blot analyses, were employed to evaluate white matter structure and changes in white matter related proteins, respectively. Furthermore, we conducted 5-ethynyl-2-deoxyuridine (EdU) labeling injections during the first week post-injury to assess whether post-injury oligodendrogenesis is related to white matter alterations at 30 dpi. Following TBI, male mice sustained higher ventricular expansion and external capsule atrophy compared to females. These changes were observed in the absence of TBI-induced cortical atrophy at 30 dpi. Regardless of age, male mice exhibited a more pronounced inflammatory response compared to females, characterized by a greater Ionized calcium-binding adaptor molecule 1 (Iba1) coverage and a higher number of Iba1+/EdU+ cells within their white matter tracts. A reduction in myelin basic protein (MBP) levels was evident in both male and female young mice but not in aged groups. When compared to young male mice, young female mice exhibited a distinct neurofilament heavy chain (NF-H) protein phosphorylation pattern, a difference absent in aged mice. Notably, while male mice showed a robust increase in newly generated mature oligodendrocytes within their white matter tracts, TBI did not induce comparable oligodendrogenesis in females. This study highlights sex- and age-related differences in white matter pathophysiology that may explain sex differences in outcomes following TBI.

Neurotrauma represents a significant global health burden with profound socioeconomic and public health implications. Beyond its clinical dimension, neurotrauma intersects with several Sustainable Development Goals (SDGs), influencing outcomes related to health, equity, infrastructure, and innovation. This scoping review aimed to map and categorize existing evidence on the relationship between neurotrauma and the SDGs following PRISMA-ScR guidelines, and to identify areas of mutual reinforcement and unmet needs. We conducted structured database searches in five electronic databases, supplemented by manual screening and a review of grey literature. Eighty-nine studies published between 2015 and 2025 were analyzed and grouped into six domains associated with the SDGs: neurotrauma care and outcomes, coverage and infrastructure, training and education, innovation and technology, international collaboration and assistance and neurotrauma prevention. The review suggests that neurotrauma care and prevention may contribute to the advancement of multiple SDGs, notably through improved patient outcomes (Goal 3), enhanced access to emergency systems (Goals 9 and 11), technological innovation (Goals 5 and 9), and the strengthening of international partnerships (Goal 17). Persistent disparities in access, research capacity, and data infrastructure were identified, particularly in low- and middle-income countries. This review maps evidence suggesting that strengthening global neurotrauma systems may support equitable progress toward the SDGs. Most identified SDG–neurotrauma linkages represent system-level inferences rather than directly measured causal effects. Future efforts should focus on equity-driven strategies, scaling collaborative models, and integrating neurotrauma indicators into global development frameworks.

Neurointensive care is moving toward more automated patient management. This study aimed to evaluate a novel external ventricular drainage (EVD) system, the VGuard® system, as a tool for intracranial pressure (ICP) monitoring and automating ventricular drainage of cerebrospinal fluid (CSF), focusing on its safety and potential to reduce complications associated with manual EVD management. This prospective, randomized clinical study was conducted in the Department of Neurosurgery at Skåne University Hospital, Lund, Sweden. Patients (aged > 18 years) with different acute brain pathologies requiring an EVD were enrolled and randomized (1:1) to receive the VGuard® system or a manual EVD. Both systems employed a ventricular probe for simultaneous intraventricular and intraparenchymal ICP monitoring. Measurement accuracy was determined by comparing the median of absolute difference in ICP, using the Mann–Whitney U test. To further investigate the accuracy of ICP measuring, a post hoc Spearman correlation test was applied. In addition, as part of a post hoc analysis, we evaluated patient outcomes. A total of 30 patients were included in the study. The VGuard® system demonstrated significantly better accuracy in ICP measurements compared with the manual EVD; median absolute difference: 1.07 versus 2.88, p < 0.001; median Spearman correlation coefficients: 0.81 versus 0.48, p < 0.05. There were no statistically significant differences in patient outcomes [mortality, Glasgow Outcome Scale-Extended (GOSE), modified Rankin Scale (mRS), median time with the EVD, and length of intensive care unit (ICU) stay], or adverse events (AE). No serious adverse events were noted. This is the first study to evaluate the VGuard® system, showing results of increased accuracy in measured ICP compared with the manual EVD. The VGuard® system offers an automated EVD solution, representing a step toward increased neurointensive care automation.

Severe traumatic brain injury (TBI) is associated with high mortality and long-term disability. Inflammation is central to TBI pathophysiology, yet early dynamics of inflammatory mediators in blood and cerebrospinal fluid (CSF) remain incompletely understood, and commonly used assay platforms have rarely been directly compared. We aimed to characterize the inflammatory response in blood and CSF during the first week after severe TBI and to assess agreement between electrochemiluminescence (ECL) and proximity extension assay (PEA). In this prospective observational study, adults with severe TBI (n = 21) were recruited. Plasma and CSF samples were collected at two time points: days 1–3 and days 4–8. Orthopedic patients with minor extremity fractures (n = 11) served as controls. Inflammatory mediator levels were quantified using ECL (11 mediators) and PEA (45 mediators). Group differences, temporal changes, and inter-platform agreement were analyzed. In plasma, 13 mediators were increased and 3 decreased, while in CSF, 19 were increased and 3 decreased during the first week post-injury. Key mediators (IL-6, IL-8, IL-10) were consistently elevated in both compartments. When comparing analytic methods, ECL and PEA showed strong cross-platform correlations for IL-8 and IL-10 in both plasma and CSF, whereas IL-13 showed weak, non-significant correlation. However, limited interchangeability between platforms and platform-related differences across compartments and time points were also observed. Severe TBI is associated with marked, temporal and compartmentalized inflammatory response during first post-injury, particularly in CSF. Comparison of ECL and PEA showed limited interchangeability, underscoring the importance of platform awareness and interpretation in TBI biomarker studies. Clinical trial number: Not applicable.

Anterior cord herniation is due to a ventral displacement of the spinal cord through a defect in the dura and/or arachnoid.1 Though the condition is rare, some case reports are available.1-3 The neurological symptoms can slowly deteriorate over several years.3 A Brown-Séquard-like syndrome is the most common presenting neurological finding.2,4 Asymptomatic cases may be discovered incidentally.4 However, when progressive neurological deficits are present, surgical exploration should be considered. Surgery is not without risks of impaired neurological function postoperatively, and intraoperative neurophysiological monitoring is important during the surgical procedure. We present a case of progressive impairment of lower extremity function, particularly gait function, due to anterior cord herniation (Video 1). The patient was initially managed conservatively, but due to rapid deterioration of motor function of the left leg accompanied by gait disturbance over the last year, surgical exploration was recommended, and the patient consented. Laminectomy was followed by dural opening. The denticulate ligament was cut for mobilization of the spinal cord, and the anterior dural defect was identified. The spinal cord could be freed and was carefully luxated from the defect, and a dural substitute was put in place to cover the dural defect. Throughout the procedure, D-wave and sensory evoked potentials could not be detected, but motor evoked potentials (MEPs) were present at the initiation of the surgery. However, the MEPs was lost during the end of the surgical procedure. Complete loss of MEPs during spinal surgery is a strong predictor of permanent deficits.5 Despite this, the patient had an uneventful recovery and could walk 700 m with crutches 3 months postoperatively, showing continuous improvement.

Many traumatic brain injury (TBI) treatment protocols, including the Lund concept, advocate the highest point of the subarachnoid space (typically the vertex) as the zero-reference point for intracranial pressure (ICP) and the level of the right atrium as the zero-reference point for mean arterial blood pressure (MAP). In 2017, at the Department of Neurosurgery in Lund, Sweden, the zero-reference points for ICP and MAP were both changed to the external auditory meatus (EAM), thus altering the calculated cerebral perfusion pressure (CPP) levels. We hypothesized that the ICP and MAP levels obtained from the different zero-reference points resulted in altered neurocritical care management and/or patient outcome. We conducted a retrospective analysis of ICP, CPP, MAP, medical management, mortality, and outcome in two different patient cohorts with severe TBI treated at the Department of Neurosurgery, Skåne University Hospital, Lund, Sweden, between 2013 and 2016 and 2018 and 2022. We collected more than 31,000 measurements from 49 patients between 2013 and 2016 and 53 patients between 2018 and 2022. Age and injury severity were similar in both groups. Mortality and treatment outcome according to the Glasgow Outcome Scale – Extended were similar. Mean ICP levels were higher (p < 0.0001) after the reference point was changed to the EAM. The use of clonidine (65

Background:Multiple clinical practice guidelines and head computed tomography decision rules exist for emergency department (ED) triage of children with traumatic brain injury (TBI). These vary in structure, aim, target cohort, and outcomes, yet are used clinically in similar populations. We compared important clinical and practical characteristics of all major guidelines in a large, real-world paediatric traumatic brain injury (TBI) cohort. Methods:Prospective, pragmatic, observational study of children (<18 years of age) presenting with mild-moderate TBI to 16 EDs in Sweden and Norway, including prospective documentation of guideline-specific risk factors and outcomes between April 2018 and May 2024. We assessed the diagnostic accuracy and characteristics of CATCH, CATCH2, CHALICE, PECARN, SNC16, PREDICT, and NICE23, both within guideline-specific application cohorts and across the full study cohort. The primary comparative outcome was significant trauma-related findings on cranial computed tomography (cCT). Secondary outcomes were neurosurgical interventions and guideline-specific endpoints. The study was registered at ClinicalTrials.gov (NCT05964764). Findings:The full cohort consisted of 3012 children (median age, 5.6 years; SD, 4.8). Among these, 0.9% (27/3012) had significant cCT findings, and 2/3012 (0.07%) required neurosurgery. CATCH and CATCH2 could be applied to 31.0% (934/3012) of patients, whereas the remaining guidelines were applicable to >94% of the cohort. In a comparative analysis concerning significant cCT findings, the lowest sensitivity estimates were 74.1% (95% CI: 53.7-88.9) for both PECARN ≥2 years and PREDICT ≥2 years; the highest was 100% (95% CI: 87.2-100.0) for SNC16. Specificity ranged from 41.6% (95% CI: 39.8-43.4) for SNC16 to 78.3% (95% CI: 76.8-79.8) for CHALICE. Mandatory cCT rates varied from 1.2% (PREDICT ≥2 years) to 29.9% (CATCH2). Interpretation:A head-to-head comparison in a real-world, paediatric, TBI cohort highlights key features of established guidelines and decision rules, offering insight into their comparative diagnostic accuracy, practical application and clinical impact. Funding:This work was supported by non-commercial state funding from Södra Sjukvårdsregionen, Vetenskapliga Rådet (Hallands Hospital), and Forskning och Utveckling Halland.

Traumatic brain injury (TBI) leads to intracerebral inflammation involving resident microglial cells and astrocytes as well as invading peripheral dendritic cells (DCs), monocytes, and neutrophils. However, the profile of immune blood cells activated by TBI remains poorly defined. Several animal models showing invasion of circulating classical dendritic cells type 2 (cDC2s) to the traumatically injured brain have been found, resulting in exacerbated neurological outcomes. In TBI patients, increased levels of chemokine CCL2, attracting cDC2 cells, have been linked to poor recovery. In the present study, blood samples from healthy blood donors (n = 11) were compared with blood from TBI patients (n = 15) at day 1 and day 3 after admission for neurointensive care stored in two tested freezing media (eight patients using Cytodelics, seven patients using CryoStor CS10) for analyses by flow cytometry. Reference blood was collected from random healthy blood donors (7 with Cytodelics, 4 CryoStor CS10). Flow cytometry excluded T-cells, B-cells, and natural killer cells by a panel of CD3, CD19, CD20, and CD56 antibodies. To identify DCs and inflammatory monocytes, antibodies to CD11c, CD1c, CD141, HLA-DR, and CD14 labeled with specific fluorochromes were added to the thawed blood samples. Neutrophils were analyzed by separate runs of flow cytometry using a CD66b antibody. Despite some differences depending on the freezing medium used, the percentage of classical DCs type 2 (cDC2; CD14-, CD11c high, CD1c+) remained unchanged from healthy controls at day 1 after admission but increased significantly (p = 0.014) from day 1 until day 3 after TBI. In contrast, levels of classical DCs type 1, inflammatory monocyte-derived DCs, or neutrophils were not altered. Thus, our preliminary data, in addition to previous animal model data, suggest a role for circulating cDC2 cells contributing negatively to the pathophysiology of TBI.

The age-specific incidence of traumatic brain injury in older adults is rising in high-income countries, mainly due to an increase in the incidence of falls. The severity of traumatic brain injury in older adults can be underestimated because of a delay in the development of mass effect and symptoms of intracranial haemorrhage. Management and rehabilitation in older adults must consider comorbidities and frailty, the treatment of pre-existing disorders, the reduced potential for recovery, the likelihood of cognitive decline, and the avoidance of future falls. Older age is associated with worse outcomes after traumatic brain injury, but premorbid health is an important predictor and good outcomes are achievable. Although prognostication is uncertain, unsubstantiated nihilism (eg, early withdrawal decisions from the assumption that old age necessarily leads to poor outcomes) should be avoided. The absence of management recommendations for older adults highlights the need for stronger evidence to enhance prognostication. In the meantime, decision making should be multidisciplinary, transparent, personalised, and inclusive of patients and relatives.

Early recognition and management of sports-related concussion (SRC), including removal from the sports activity, is essential for player safety and to prevent long-term symptoms. A graduated, stepwise rehabilitation protocol is implemented to allow the athlete to return to sports. In 2022, the 6th international consensus statement on concussion in sports was presented, which has now been adapted to Swedish conditions. In the present overview, the updated recommendations for SRC in athletes are summarized.

Traumatic brain injury (TBI) often leads to impaired regulation of cerebral blood flow, which may be caused by pathological changes of the vascular smooth muscle cells (VSMCs) in the arterial wall. Moreover, these cerebrovascular changes may contribute to the development of various neurodegenerative disorders such as Alzheimer's-like pathologies that include amyloid beta aggregation. Despite its importance, the pathophysiological mechanisms responsible for VSMC dysfunction after TBI have rarely been evaluated. Here, we show that acute human TBI resulted in early pathological changes in leptomeningeal arteries, closely associated with a decrease in VSMC markers such as NOTCH3 and alpha smooth muscle actin (α-SMA).These changes coincided with increased aggregation of variable-length amyloid peptides including Aβ1-40/42, Aβ1-16, and β-secretase-derived fragment (βCTF) (C99) caused by altered processing of amyloid precursor protein (APP) in VSMCs. The aggregation of Aβ1-40/42 peptides were also observed in the leptomeningeal arteries of young TBI patients. These pathological changes also included higher β-secretase (BACE1) when compared to α-secretase A Disintegrin And Metalloprotease 10 (ADAM10) expression in the leptomeningeal arteries, plausibly caused by hypoxia and oxidative stress as shown using human VSMCs in vitro. Importantly, BACE1 inhibition not only restored NOTCH3 signalling but also normalized ADAM10 levels in vitro. Furthermore, we found reduced ADAM10 activity and decreased NOTCH3, along with increased βCTF (C99) levels in mice subjected to an experimental model of TBI. This study provides evidence of early post-injury changes in VSMCs of leptomeningeal arteries that can contribute to vascular dysfunction and exacerbate secondary injury mechanisms following TBI.

Axonal injuries commonly contribute to poor functional outcomes following traumatic brain injury (TBI). To assess cerebral blood flow (CBF) and energy metabolic disturbances in a TBI model of widespread axonal injury, we exposed 105 adult mice to the central (midline) fluid percussion injury (cFPI) diffuse TBI model, or sham injury, and used 9.4 T magnetic resonance (MR) arterial spin labeling (ASL), cortical and hippocampal mitochondrial respiration, and hippocampal MR spectroscopy at 1- and 7-days post-injury (dpi). Widespread, bilateral CBF reductions were observed at day 1 dpi, changes that were normalized by 7 dpi. However, cortical and hippocampal mitochondrial respiration and reactive oxygen species (ROS) production was not significantly altered at 1 and 7 dpi. Moreover, hippocampal volumes, evaluated by MRI, were not altered by cFPI, and by immunohistochemistry only a few apoptotic hippocampal cells were observed. By MRS, evidence of delayed (7 dpi) membrane disruption (phosphocholine and glycerophosphocholine) and glutamate/glutamine increase were observed. While widespread traumatic axonal pathology associated with functional impairments is observed in this TBI model, early CBF alterations were transient and did not translate into significant energy metabolic disturbances. Instead, the delayed hippocampal metabolite changes observed by MRS may contribute to the functional impairment observed in this diffuse TBI model.