Background Locomotor training of rats with thoracic contusion spinal cord injuries can induce task-specific changes in stepping but rarely results in improved overground locomotion, possibly due to a ceiling effect. Thus, the authors hypothesize that incompletely injured rats maximally retrain themselves while moving about in their cages over the first few weeks postinjury. Objective To test the hypothesis using hindlimb immobilization after mild thoracic contusion spinal cord injury in adult female rats. A passive stretch protocol was included as an independent treatment. Methods Wheelchairs were used to hold the hindlimbs stationary in an extended position leaving the forelimbs free. The wheelchairs were used for 15 to 18 hours per day, 5 days per week for 8 weeks, beginning at 4 days postinjury. A 20-minute passive hindlimb stretch therapy was applied to half of the animals. Results Hindlimb locomotor function of the wheelchair group was not different from controls at 1 week postinjury but declined significantly over the next 4 weeks. Passive stretch had no influence on wheelchair animals but limited functional recovery of normally housed animals, preventing them from regaining forelimb–hindlimb coordination. Following 8 weeks of wheelchair immobilization and stretch therapy, only the wheelchair group displayed an improvement in function when returned to normal housing but retained significant deficits in stepping and coordination out to 16 weeks. Conclusion Hindlimb immobilization and passive stretch may hinder or conceal the normal course of functional recovery of spinal cord injured rats. These observations have implications for the management of acute clinical spinal cord injuries.

Background Stretching is a widely accepted standard-of-care therapy following spinal cord injury that has not been systematically studied in animal models. Objective To investigate the influence of a daily stretch-based physical therapy program on locomotor recovery in adult rats with moderate T9 contusive SCI. Methods A randomized treatment and control study of stretching in an animal model of acute spinal cord injury (SCI). Moderate spinal cord injuries were delivered with the NYU Impactor. Daily stretching (30 min./day, 5 days/wk for 8 wks) was provided by a team of animal handlers. Hindlimb function was assessed using the BBB Open Field Locomotor Scale and kinematically. Passive range-of-motion for each joint was determined weekly using a goniometer. Results Declines in hindlimb function during overground stepping were observed for the first 4 weeks. BBB scores improved weeks 5–10 but remained below the control group. Stretched animals had significant deficits in knee passive ROM starting at week 4 and for the duration of the study. Kinematic assessment showed decreased joint excursion during stepping that partially recovered beginning at week 5. Conclusion Stretch-based therapy significantly impaired functional recovery in adult rats with a moderate contusive SCI at T10. The negative impact on function was greatest acutely, but persisted even after the stretching ceased at 8 weeks post-injury.

Simvastatin, the fourth drug selected for testing by Operation Brain Trauma Therapy (OBTT), is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor used clinically to reduce serum cholesterol. In addition, simvastatin has demonstrated potent antineuroinflammatory and brain edema reducing effects and has shown promise in promoting functional recovery in pre-clinical models of traumatic brain injury (TBI). The purpose of this study was to assess the potential neuroprotective effects of oral administration of simvastatin on neurobehavioral, biomarker, and histopathological outcome measures compared across three pre-clinical TBI animal models. Adult male Sprague-Dawley rats were exposed to either moderate fluid percussion injury (FPI), controlled cortical impact injury (CCI), or penetrating ballistic-like brain injury (PBBI). Simvastatin (1 or 5 mg/kg) was delivered via oral gavage at 3 h post-injury and continued once daily out to 14 days post-injury. Results indicated an intermediate beneficial effect of simvastatin on motor performance on the gridwalk (FPI), balance beam (CCI), and rotarod tasks (PBBI). No significant therapeutic benefit was detected, however, on cognitive outcome across the OBTT TBI models. In fact, Morris water maze (MWM) performance was actually worsened by treatment in the FPI model and scored full negative points for low dose in the MWM latency and swim distance to locate the hidden platform. A detrimental effect on cortical tissue loss was also seen in the FPI model, and there were no benefits on histology across the other models. Simvastatin also produced negative effects on circulating glial fibrillary acidic protein biomarker outcomes that were evident in the FPI and PBBI models. Overall, the current findings do not support the beneficial effects of simvastatin administration over 2 weeks post-TBI using the oral route of administration and, as such, it will not be further pursued by OBTT.

Glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) may aid in the evaluation of traumatic brain injury (TBI). The objective of this analysis was to compare GFAP and UCH-L1 values measured using a handheld device compared with a core laboratory platform. We analyzed plasma samples from patients with TBI and healthy controls enrolled in the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) cohort study. GFAP and UCH-L1 were measured twice in each subject using prototype assays, first with the Abbott i-STAT TM handheld device, and second with the Abbott ARCHITECT â platform. We then quantified the agreement in biomarker values obtained using these two methods. GFAP and UCH-L1 were measured twice in 570 and 572 samples, respectively. GFAP values measured by the ARCHITECT platform (median 143.3 [interquartile range (IQR): 19.8-925.8] pg/mL) were higher than values measured by the i-STAT (median 116.0 [IQR: 9.2-856.5] pg/mL). GFAP values from the two platforms were strongly correlated ( p = 0.985). Similarly, UCH-L1 values measured by the ARCHITECT platform (median 163.9 [IQR: 82.5-412.4] pg/mL) were higher than values measured by the i-STAT (median 122.5 [IQR: 63.0-297.3] pg/mL). UCH-L1 values from the two platforms were strongly correlated ( p = 0.933). Passing-Bablok regression equations were developed to estimate the relationship between the two platforms, specifically to predict i-STAT values from the ARCHITECT platform. GFAP and UCH-L1 values measured using the prototype assays on the Abbott i-STAT and ARCHITECT platforms are strongly correlated and values from either platform may be converted to the other.

This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

The Morris water maze (MWM) task is one of the most widely used and versatile tools in behavioral neuroscience for evaluating spatial learning and memory. With regard to detecting cognitive deficits following central nervous system (CNS) injuries, MWM has been commonly utilized in various animal models of neurotrauma, such as fluid percussion injury (FPI), cortical controlled impact (CCI) injury, weight-drop impact injury, and penetrating ballistic-like brain injury (PBBI). More importantly, it serves as a therapeutic index for assessing the efficacy of treatment interventions on cognitive performance following neurotrauma. Thus, it is critical to design an MWM testing paradigm that is sensitive yet discriminating for the purpose of evaluating potential therapeutic interventions. In this chapter, we discuss how multiple test manipulations, including the size of platform, numbers of trials per day, the frequency of retesting intervals, and the texture of platform surface, impact MWM's ability to detect cognitive deficits using a rat model of PBBI.

These findings support the dual anti- seizure and neuroprotective role of LEV, but more importantly identify the importance of an extended dosing protocol which was specific to the therapeutic targets studied.

BACKGROUND:Traumatic brain injury (TBI) is prevalent and highly morbid among Service Members. A better understanding of TBI epidemiology, outcomes, and care patterns in deployed settings could inform potential approaches to improve TBI diagnosis and management. METHODS:A retrospective cohort analysis of Service Members who sustained a TBI in deployed settings between 2001 and 2018 was conducted. Among individuals hospitalized with TBI, we compared the demographic characteristics, mechanism of injury, injury type, and severity between combat and noncombat injuries. We compared diagnostic tests and procedures, evacuation patterns, return to duty rates and days in care between individuals with concussion and those with severe TBI. RESULTS:There were 46,309 service members with TBI and 9,412 who were hospitalized; of those hospitalized, 55% (4,343) had isolated concussion and 9% (796) had severe TBI, of whom 17% (132/796) had multiple injuries. Overall mortality was 2% and ranged from 0.1% for isolated concussion to 18% for severe TBI. The vast majority of TBI were evacuated by rotary wing to role 3 or higher, including those with isolated concussion. As compared with severe TBI, individuals with isolated concussion had fewer diagnostic or surgical procedures performed. Only 6% of service members with severe TBI were able to return to duty as compared with 54% of those with isolated concussion. Traumatic brain injury resulted in 123,677 lost duty days; individuals with isolated concussion spent a median of 2 days in care and those with severe TBI spent a median of 17 days in care and a median of 6 days in the intensive care unit. CONCLUSION:While most TBI in the deployed setting are mild, TBI is frequently associated with hospitalization and multiple injuries. Overtriage of mild TBI is common. Improved TBI capabilities applicable to forward settings will be critical to the success of future multidomain operations with limitations in air superiority.