Journal of neurotrauma最新文献

After traumatic brain injury (TBI), monocyte/macrophage infiltration is a key early step in the development of an inflammatory cascade that leads to substantial secondary damage. Intravenous (IV) immunomodulatory nanoparticle (IMP) administration after TBI limits inflammatory cell infiltration and reduces both behavioral decline and lesion size without any noticeable toxicity. Here we show that there is a dose-response relationship between the amount of IMP administered and tissue damage which plateaus at a well-tolerated dose. There is a therapeutic window of efficacy for IMP administration of at least 6 h after injury with some benefit observed when treatment was delayed for 12 h after injury. Single cell RNA sequencing demonstrated substantial changes in gene expression after TBI in both neural and non-neural cells in the brain, and IMP administration ameliorated many of the changes. Particularly notable were significant unexpected changes in CCR1, CXCR2, and BDNF expression in vascular smooth muscle cells that may participate in injury responses after TBI. Thus, IMP treatment within 6 h after TBI limits inflammatory responses and gliosis, improves anatomical and behavioral outcomes and prevents detrimental changes in gene expression in both neural and non-neural cellular elements of the brain. IMPs are non-toxic and are made of an FDA-approved material that is stable at room temperature. They could easily be given IV immediately after TBI in the field by emergency medical technicians or in the emergency room to prevent secondary damage, thereby improving outcomes.

Pre-clinical vertebrate models of traumatic brain injury (TBI) routinely use anesthetics for animal welfare; however, humans experience TBI without anesthetics. Therefore, translation of findings from vertebrate models to humans hinges on understanding how anesthetics influence cellular and molecular events that lead to secondary injuries following TBI. To investigate the effects of anesthetics on TBI outcomes, we used an invertebrate Drosophila melanogaster model to compare outcomes between animals exposed or not exposed to anesthetics prior to the same primary injury. Using a common laboratory fly line, w¹¹¹⁸, we found that exposure to the volatile anesthetics isoflurane or sevoflurane, but not ether, prior to TBI produced a dose-dependent reduction in mortality within 24 h following TBI. Thus, isoflurane and sevoflurane precondition w¹¹¹⁸ flies to deleterious effects of TBI. To examine the effects of genetic differences on anesthetic preconditioning of TBI, we repeated the experiment with the Drosophila Genetic Reference Panel (DGRP) collection of genetically diverse, inbred fly lines. Pre-exposure to either isoflurane or sevoflurane revealed a wide range of preconditioning levels among 171 and 144 DGRP lines, respectively, suggesting a genetic component for variation in anesthetic preconditioning of mortality following TBI. Finally, genome-wide association study analyses identified single-nucleotide polymorphisms in genes associated with isoflurane or sevoflurane preconditioning of TBI. Several of the genes, including the fly ortholog of mammalian Calcium Voltage-Gated Subunit Alpha1 D (CACNA1D), are highly expressed in neurons and are functionally linked to both anesthetics and TBI. These data indicate that anesthetic dose and genetic background should be considered when investigating effects of anesthetics in vertebrate TBI models, and they support use of the fly model for elucidating the mechanisms underlying anesthetic preconditioning of TBI.

Control over symptoms postconcussion is central to an active self-directed recovery process. Therefore, assessing a patient's confidence in controlling their symptoms and facilitating their concussion recovery is an important component of treatment. Previously, no measures existed to assess symptom-specific self-efficacy (SE) in pediatric concussion recovery. SE is an individual's belief or confidence in their capabilities to execute action plans necessary to perform certain behaviors. Based on this definition, we developed the Progressive Activities of Controlled Exertion-Self-Efficacy (PACE-SE) scale to measure a patient's SE related to pediatric concussion recovery-specific activities. The aim of this article is to present the psychometric characteristics (evidence of reliability, validity) of the PACE-SE scale. The 17-item PACE-SE was administered to children and adolescents, 10-18 years of age, recovering from a diagnosed concussion as part of a standard clinical evaluation. Results revealed a four-factor structure producing the following scales: Managing My Stress, Managing My Activity, Seeking Adult Assistance, and Maintaining Positive Outlook. The PACE-SE scores indicated excellent internal consistency reliability with reasonable test-retest reliability over time. Evidence for the association between recovery status and greater confidence and control over recovery-related activities as measured by the PACE-SE was supported by: (1) an inverse association with symptom status reflecting lower confidence for managing recovery with higher symptom load, (2) greater reported problems with school performance associated with lower SE, (3) positive change in SE ratings across two clinic visits associated with symptom improvement, and (4) a significant difference in SE ratings evident between recovered and nonrecovered patients. The psychometric evidence supporting the PACE-SE scale provides the clinician with a measure to understand the child/adolescent patient's self-confidence in facilitating their concussion recovery.

Visual feedback training (VFT) plays an important role in the motor rehabilitation of patients with spinal cord injury (SCI). However, the neural mechanisms are unclear. We aimed to investigate the changes in dynamic functional network connectivity (FNC) related to visual networks (VN) in patients with SCI and to reveal the neural mechanism of VFT promoting motor function rehabilitation. Dynamic FNC and the sliding window method were performed in 18 complete SCI (CSCI), 16 patients with incomplete SCI (ISCI), and 42 healthy controls (HCs). Then, k-mean clustering was implemented to identify discrete FNC states, and temporal properties were computed. The correlations between these dynamic features and neurological parameters in all patients with SCI were calculated. The majority of aberrant FNC was manifested between VN and executive control network (ECN). In addition, compared with HCs, temporal metrics derived from state transition vectors were decreased in patients with CSCI including the mean dwell time and the fraction of time spent in state 3. Furthermore, the disrupted FNC between salience network and ECN in state 2 and the number of transitions were all positively correlated with neurological scores in patients with SCI. Our findings indicated that SCI could result in VN-related FNC alterations, revealing the possible mechanism for VFT in rehabilitation of patients with SCI and increasing the training efficacy and promoting rehabilitation for SCI.

Mental health conditions and concussion history reported by a collegiate athlete may contribute to prolonged recovery and symptom severity after concussion. This work examined the potential associations among concussion history, preexisting conditions, and sex relative to initial symptom severity and recovery duration following sport-related concussion (SRC) in a cohort of Division 1 National Collegiate Athletic Association athletes. This prospective cohort study analyzed symptom severity, recovery, and return-to-play (RTP) times reported post-SRC using data collected as part of the Pac-12 Concussion Assessment, Research and Education Affiliated Program and Health Analytics Program. Health history questionnaires that included self-reported history of preexisting conditions were completed at baseline. When consented athletes were diagnosed with a concussion, daily postconcussion symptom scores were evaluated until an athlete was clinically determined to be asymptomatic. Generalized linear and Cox proportional hazards models were used to determine associations between preexisting conditions and recovery and RTP times. Ninety-two concussions met inclusion criteria. Notable differences in initial symptom severity existed between females and males who had mood disorders (effect size [d] = 0.51) and attention-deficit hyperactivity disorder (ADHD; d = 0.93). The number of previous concussions was a strong predictor of athletes reporting preexisting mood disorders, depression, anxiety, and ADHD (p = 0.008-0.04). Females with ≥2 previous concussions required more days to RTP than males (d = 0.31-0.72). Weekly recovery and RTP probabilities substantially differed between athletes who did or did not have learning disorders (LDs; hazard ratio [HR]_Recovery = 0.32, HR_RTP = 0.22, d = 1.96-2.30) and ADHD (HR_Recovery = 3.38, HR_RTP = 2.74, d = 1.71-4.14). Although no association existed between concussion history and acute symptom severity, collegiate athletes with a history of concussion had higher probabilities of reporting depression, mood disorders, anxiety, and ADHD. Having ADHD or LDs likely strongly affects time to recovery and RTP for collegiate athletes.

Deep vein thrombosis and pulmonary embolism prophylaxis is an important part of trauma care. Despite an increased risk of thrombotic complications, the use of venous thrombosis chemoprophylaxis in penetrating traumatic brain injury (pTBI) patients is met with reluctance from neurosurgeons because of concern for the exacerbation of intracerebral hemorrhage. The objective of this study was to provide initial pre-clinical evidence of the effects of Lovenox (LVX) administration following pTBI with significant intracerebral hemorrhage. Sprague-Dawley rats received a penetrating ballistic-like brain injury. Animals were randomly divided into two groups following injury: LVX (25 mg/kg) or vehicle (VEH, saline). LVX or vehicle was administered subcutaneously beginning 24 h after the injury and continued daily for 7 days post-injury. A neurological assessment was performed daily and magnetic resonance imaging (MRI) was performed at baseline, 1, 2, 3, and 7 days post-injury. Following the final MRI, brains were isolated and prepared for histological analysis. Thromboelastography demonstrated dramatic anticoagulation effects which were confirmed by significant increases in partial thromboplastin time (p < 0.001). Daily neurological assessment revealed no worsening of functional deficits following LVX treatment. MRI analysis demonstrated no differences in cerebral edema or intracranial hemorrhage volumes between treatment groups at any tested post-injury time points. However, LVX elicited a significant reduction in fibrin deposition in the ipsilateral striatum and lesion site at 7 days post-injury (p < 0.05). Serum levels of beta-amyloid were decreased at 7 days following LVX treatment (p < 0.05) which may indicate neuroprotective effects but was not correlated to brain levels. The results presented indicate that administration of LVX at a dose capable of inducing anticoagulation is safe in a rodent model of pTBI without exacerbation of intracerebral hemorrhage within the first 7 days of injury.