Traumatic brain injury (TBI), and particularly concussion, is a major concern for the U.S. Military because of the associated short term disability, long term cognitive and pain symptoms suffered by some, and risk of prolonged or permanent neurologic injury if the Service member incurs a second TBI before full recovery from the first. Concussions were seen more often during the recent conflicts in Afghanistan and Iraq than in prior conflicts, such as the Vietnam War, because of the use of improvised explosive devices that typically caused non-penetrating closed head injury. Since 2000 more than 300,000 Service members were diagnosed with TBI, of which more than 80 % were concussions. Improved TBI screening tools also have identified a higher than expected incidence of concussions occurring in garrison. In this review we summarize current epidemiologic data for TBI in the Military, and describe contemporary Military procedures and strategies for TBI prevention, identification, evaluation, and acute and chronic care. Key TBI clinical research priorities and programs are described, and innovative organizational plans to address future TBI needs are summarized.

Neural progenitor cells (NPCs) have been investigated as potential vehicles for brain tumor therapy because they have been shown to migrate toward central nervous system gliomas and can be genetically engineered to deliver cytotoxic agents to tumors. The mechanisms that regulate migration of NPCs to tumors are not fully understood. By means of microarray analysis, polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemistry, we found that monocyte chemoattractant protein-1 (MCP-1/CCL-2) was expressed in experimental brain tumor cells in vivo and in vitro. CCR2, the receptor for MCP-1, was expressed on C17.2 NPCs. We used a modified Boyden chamber assay and found increased migration of NPCs in vitro in response to MCP-1. By means of an in vivo model for NPC migration, we found evidence of NPC migration toward areas of MCP-1 infusion in rat brains. An understanding of NPC migration mechanisms may be used to enhance delivery of cytotoxic agents to brain tumor cells.

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In the adult rodent brain, neural progenitor cells migrate from the subventricular zone of the lateral ventricle towards the olfactory bulb in a track known as the rostral migratory stream (RMS). To facilitate the study of neural progenitor cells and stem cell therapy in large animal models of CNS disease, we now report the location and characteristics of the normal canine and feline RMS. The RMS was found in Nissl-stained sagittal sections of adult canine and feline brains as a prominent, dense, continuous cellular track beginning at the base of the anterior horn of the lateral ventricle, curving around the head of the caudate nucleus and continuing laterally and ventrally to the olfactory peduncle before entering the olfactory tract and bulb. To determine if cells in the RMS were proliferating, the thymidine analog 5-bromo-2-deoxyuridine (BrdU) was administered and detected by immunostaining. BrdU-immunoreactive cells were present throughout this track. The RMS was also immunoreactive for markers of proliferating cells, progenitor cells and immature neurons (Ki-67 and doublecortin), but not for NeuN, a marker of mature neurons. Luxol fast blue and CNPase staining indicated that myelin is closely apposed to the RMS along much of its length and may provide guidance cues for the migrating cells. Identification and characterization of the RMS in canine and feline brain will facilitate studies of neural progenitor cell biology and migration in large animal models of neurologic disease.

BACKGROUND The US Military has achieved the highest casualty survival rates in its history. However, there remain multiple areas in combat trauma that present challenges to the delivery of high-quality and effective trauma care. Previous work has identified research priorities for pre-hospital care, but there has been no similar analysis for forward surgical care. METHODS A list of critical “focus areas” was developed by the Committee on Surgical Combat Casualty Care (CoSCCC). Individual topics were solicited and mapped to appropriate focus areas by group consensus and review of Eastern Association for the Surgery of Trauma (EAST) and Joint Trauma System guidelines. A web-based survey was distributed to the CoSCCC and the military committees of EAST and the American Association for the Surgery of Trauma. Topics were rated on a Likert scale from 1 (low) to 10 (high priority). Descriptives, univariate statistics, and inter-rater correlation analysis was performed. RESULTS 13 research focus areas were identified (eight clinical and five adjunctive categories). Ninety individual topics were solicited. The survey received 64 responses. The majority of respondents were military (90%) versus civilians (10%). There was moderate to high agreement (inter-rater correlation coefficient = 0.93, p < 0.01) for 10 focus areas. The top five focus areas were Personnel/Staffing (mean, 8.03), Resuscitation and Hemorrhage Management (7.49), Pain/Sedation/Anxiety Management (6.96), Operative Interventions (6.9), and Initial Evaluation (6.9). The “Top 10” research priorities included four in Personnel/Staffing, four in Resuscitation/Hemorrhage Management, and three in Operative Interventions. A complete list of the topics/scores will be presented. CONCLUSIONS This is the first objective ranking of research priorities for combat trauma care. The “Top 10” priorities were all from three focus areas, supporting prioritization of personnel/staffing of austere teams, resuscitation/hemorrhage control, and damage-control interventions. This data will help guide Department of Defense research programs and new areas for prioritized funding of both military and civilian researchers. LEVEL OF EVIDENCE Study design, level IV.

Department of Defense and service-specific policies introduced between 2006 and 2013 significantly increased the number of battlefield TBIs identified, successfully improving the longstanding problem of underreporting of TBIs.

Background: Clinical recommendations for concussion management encourage reduced cognitive and physical activities immediately after injury, with graded increases in activity as symptoms resolve. Empirical support for the effectiveness of such recommendations is needed. Purpose: To examine whether training medical providers on the Defense and Veterans Brain Injury Center’s Progressive Return to Activity Clinical Recommendation (PRA-CR) for acute concussion improves patient outcomes. Study Design: Cohort study; Level of evidence, 2. Methods: This study was conducted from 2016 to 2018 and compared patient outcomes before and after medical providers received an educational intervention (ie, provider training). Patients, recruited either before or after intervention, were assessed at ≤72 hours, 1 week, 1 month, 3 months, and 6 months after a concussion. The participant population included 38 military medical providers and 106 military servicemembers with a diagnosed concussion and treated by one of the military medical providers: 58 patient participants received care before the intervention (ie, provider training) and 48 received care after intervention. The primary outcome measure was the Neurobehavioral Symptom Inventory. Results: The patients seen before and after the intervention were predominantly male (89.7% and 93.8%, respectively) of military age (mean ± SD, 26.62 ± 6.29 years and 25.08 ± 6.85 years, respectively) and a mean ± SD of 1.92 ± 0.88 days from injury. Compared with patients receiving care before intervention, patients receiving care after intervention had smaller increases in physical activities (difference in mean change; 95% CI, 0.39 to 6.79) and vestibular/balance activities (95% CI, 0.79 to 7.5) during the first week of recovery. Although groups did not differ in symptoms at ≤72 hours of injury ( d = 0.22; 95% CI, –2.21 to 8.07), the postintervention group reported fewer symptoms at 1 week ( d = 0.61; 95% CI, 0.52 to 10.92). Postintervention patients who completed the 6-month study had improved recovery both at 1 month ( d = 1.55; 95% CI, 5.33 to 15.39) and 3 months after injury ( d = 1.10; 95% CI, 2.36 to 11.55), but not at 6 months ( d = 0.35; 95% CI, 5.34 to 7.59). Conclusion: Training medical providers on the PRA-CR for management of concussion resulted in expedited recovery of patients.

Over the past 8 years, advances in the US Military Health System (MHS) have led to extensive changes in the way combat casualty care is provided to deployed service members with a traumatic brain injury (TBI). Changes include the application of cutting-edge Clinical Practice Guidelines, use of pioneering technologies, and advances in evacuation procedures. Compared with previous engagements, current operations occur on a much smaller scale, and more frequently in austere environments, such that effective medical support is increasingly challenging. In this paper, the authors describe key aspects of the current continuum of TBI care in the US military, from the point of injury through rehabilitation, with an emphasis on how emerging technologies and evidence-based Clinical Practice Guidelines assist MHS clinicians with providing the best clinical care possible in the changing battlefield.