Journal of NeurotraumaVol. 34, No. 13 AbstractsFree AccessAbstracts from The 35th Annual National Neurotrauma Symposium July 7–12, 2017 Snowbird, UtahPublished Online:1 Jul 2017https://doi.org/10.1089/neu.2017.29011.abstractsAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Trainee Competition FinalistsT01-01 SMART HUMAN NEURAL STEM CELLS TO MODIFY SCAR AND OPTIMIZE REGENERATION AFTER TRAUMATIC CERVICAL SPINAL CORD INJURYAhuja Christopher1,2, Khazaei Mohamad2, Baig Sara2, Merchant Jainetri2, Chan Priscilla2, Fehlings Michael1,21University of Toronto, Neurosurgery, Toronto, Canada2Genetics and Development, University Health Network, Toronto, CanadaHuman induced pluripotent stem cell-derived neural stem cells (hiPS-NSCs) represent an exciting therapeutic strategy for traumatic spinal cord injury (SCI) as they can replace lost neural circuits, remyelinate denuded axons and provide local trophic support. Unfortunately, most patients are in the chronic phase of their injuries where dense chondroitin sulfate proteoglycan (CSPG) scarring significantly impairs neurite outgrowth and regenerative cell migration. Several scar-modifying enzymes have been shown to synergistically enhance NSC-mediated recovery, however, nonspecific intrathecal administration can produce off-target effects. We aimed to generate a genetically-engineered line of hiPS-NSCs, termed Spinal Microenvironment Modifying and Regenerative Therapeutic (SMaRT) cells, uniquely capable of expressing a scar-modifying enzyme within the host environment to enhance functional recovery. A proprietary enzyme was non-virally integrated into hiPS-NSCs and a monocloncal line of SMaRT cells was generated and extensively characterized. The expressed enzyme rapidly degrades CSPGs on biochemical assays and allows neurons to extend into CSPG-rich regions in vitro. Furthermore, unlike wild-type hiPS-NSC media, conditioned SMaRT cell media can degrade post-injury rodent CSPGs in ex vivo injured cord cryosections. T-cell deficient rats (N = 60) with translationally-relevant chronic C6-7 clip-contusion injuries have been randomized to receive: (1) vehicle, (2) hiPS-NSCs, (3) SMaRT cells, or (4) sham surgery (laminectomy). While blinded sensorimotor behavioural assessments and rehabilitation are ongoing with a long-term 32-week endpoint, interim histologic analysis shows that grafted human cells are extending remarkably long (≥ 20,000 μm) axons along host white matter tracts in the rostral and caudal directions. This work provides exciting proof-of-concept data that genetically-engineered SMaRT cells can degrade CSPGs in vitro and that human NSC transplants can grow long axons in chronic cervical SCI to potentially form a bridge for sensorimotor signal transmission. This work is generously supported by the Canadian Institutes of Health Research, Phillip and Peggy DeZwirek, OIRM, and the Krembil Foundation.Keywords: Chronic, Glial scar, Neural precursor cell, RehabilitationT01-02 QUANTIFYING 3D WHOLE BRAIN DEFORMATION USING SONOMICROMETRY DURING DYNAMIC HEAD ROTATIONAL LOADINGAlshareef Ahmed, Giudice J. Sebastian, Forman Jason, Panzer Matthew B.University of Virginia, Center for Applied Biomechanics, Charlottesville, USAUnderstanding the mechanical response of the human brain during impact is crucial to predicting injury severity and elucidating injury mechanisms. Currently, finite element models of the human brain are the state-of-the-art technique for assessing brain injury risk, investigating potential TBI mechanisms, and developing preventative mechanisms. However, they have been developed using limited experimental data quantifying relative brain-skull motion during head impacts. The objective of this study was to develop a methodology to quantify the 3D deformation of cadaveric brain specimens in situ during high-rate rotational head motion. An array of neutrally-dense sonomicrometry crystals were implanted into the brain of a single cadaveric head specimen (male, 53 years, 116 kg, 173 cm). These crystals are capable of transmitting and receiving ultrasonic pulses where the ultrasonic time-of-flight is used to determine the distance between each crystal pair. Eight transmitting crystals were affixed to the inner skull, and 24 receiving crystals were implanted in the brain. Dynamic 3D spatial time-history data for each receiving crystal was calculated using trilateration and reported as brain tissue motion relative to the skull. Four purely rotational motion conditions, ranging from a peak angular velocity of 20–40 rad/s with a duration of 30–60 ms, were applied to the same cadaveric head/brain specimen in the three anatomic planes. This is the first study to quantify 3D brain deformation in one specimen in response to varying severity rotations in all three anatomical planes using sonomicrometry. Sonomicrometry provided highly repeatable 3D displacement data of the dynamic motion of the brain. Brain deformation response was dependent on peak angular velocity, duration, and loading direction – axial rotation resulted in the greatest deformation. Peak-to-peak displacement reached as high as 23 mm in the most severe case. The transient response of the brain lasted between 100–200 ms. The natural frequency of the brain markers was found to be 12–20 Hz. Funding was provided under NHTSA contract number DTNH221500022/0002.Keywords: mTBI/Concussion, Brain Deformation, Sonomicrometry, Finite Element ValidationT01-03 EARLY SURGICAL INTERVENTION AMONG PATIENTS WITH ACUTE CENTRAL CORD SYNDROME IS NOT ASSOCIATED WITH HIGHER MORTALITYGodzik Jake1, Dalton Jay2, Mauria Rohit1, Chapple Kristina1, Cook Alan3, Turner Jay11Barrow Neurological Institute, Department of Neurosurgery, Phoenix, USA2Washington University School Of Medicine, Department of Neurosurgery, St. Louis, USA3Chandler Regional Hospital, Department of Trauma, Chandler, USAIntroduction: Conflicting reports exist regarding mortality and morbidity of early surgical intervention for Acute Central Cord Syndrome (ACS) in multisystem trauma. As a result, the optimal timing of decompression in acute central cord syndrome (ACS) in patients with multisystem trauma remains controversial.Methods: We performed a retrospective cohort study using the National Trauma Data Bank (NTDB, years 2011–2014), including patients >18, with ACS (identified using ICD-9). Information was collected on demographics, mechanism of injury, timing of surgery (≤ 24 hours, >24 hours), Charlson Comorbidity index (CCI), and injury severity index (ISS). Logistic regression and propensity were used to evaluate relationship between hospital mortality and surgical timing.Results: 2383 patients with ACS following trauma were identified. The average age was 56 ± 15, and 79.3% were male, with an average ISS of 19.5 ± 9.0, and mortality rate of 3.0% (72). A total of 731 (30.6%) patients underwent surgery for ACS within 24 hours. Univariate analysis did not demonstrate significantly higher mortality rate in the early surgery group (p = 0.127), although the early surgery group demonstrated significantly higher ISS (20.1 vs 19.2, p = 0.04), lower CCI (2.1 vs 2.6, p < 0.001), and younger age (53.1 vs 57.7, p < 0.001). Binary logistic regression demonstrated higher ISS (OR 1.05, p < 0.001), higher CCI (OR 1.84, p < 0.001), and days to surgery (OR 0.89, p = 0.027) as significant predictors of mortality. Propensity score weighting demonstrated no significant relationship between days to surgery and in-hospital mortality (P = 0.138).Conclusions: Delayed surgical intervention does not appear to reduce mortality among patients with acute central cord syndrome. We theorize that survival in the NTDB is confounded by multisystem trauma and existing comorbidities, rather than choice of surgical timing. Delaying definitive surgical care may predispose patients to worsened disposition and greater neurological morbidity.Keywords: central cord syndrome, national trauma data bank, mortalityT01-04 HEAD-TO-HEAD COMPARISON OF POPULAR CLINICAL ASSESSMENTS TOOLS USED IN THE MANAGEMENT OF SPORT-RELATED CONCUSSION (SRC)Guzowski Nicholas, McCrea Michael A., Nelson Lindsay D.Medical College of Wisconsin, Neurosurgery, Milwaukee, USAFormal clinical testing has become widespread in the assessment and management of athletes with sport-related concussion (SRC). A variety of assessments tools are available to assess the symptoms, cognitive, postural stability, and other impairments that can arise after injury. Yet there are limited data directly comparing the performance of differing assessment tools from which clinicians can identify the most sensitive measures for clinical use. The aims of this study were to compare the sensitivity of an array of clinical assessment tools to SRC and, secondarily, to explore patterns of heterogeneity across athletes in clinical domains affected by SRC in order to inform recommendations about the multidimensional clinical assessment of SRC. Male football players (N = 917) enrolled in Project Head-to-Head II at preseason examinations, where they completed assessments of symptoms, cognitive performance, oculomotor functioning, and postural stability. Participants who sustained SRCs (n = 60) and matched non-injured controls (n = 64) underwent repeat assessments at 24–48 hours and at days 8, 15, and 45 post-injury. Measures of oculomotor and vestibular functioning were the most sensitive performance metrics to SRC (King-Devick Test and Balance Error Scoring System area under the ROC curve, AUCs, at 24–48 hours = .75 and .73, respectively, p's <.01). Additionally, memory performance as measured by the computerized Immediate Post-Concussion and Cognitive Testing (ImPACT) battery was sensitive to SRC to a lesser degree (AUC = .61, p = .036), while computerized and paper-and-pencil measures of attention, processing speed, and executive functioning (e.g., Standardized Assessment of Concussion, Trail Making Test, Wechsler Adult Intelligence Scale-IV Processing Speed Index) did not significantly distinguish SRC from control subjects. Evaluation of patterns of impairment among subjects across clinical domains revealed significant heterogeneity in the clinical manifestations of SRC. The data help to identify the assessment tools with the strongest overall sensitivity to SRC while also supporting the multidimensional assessment of athletes with SRC.Keywords: Sport-related Concussion, Neuropsychological Testing, Multidimensional Assessment, Oculomotor FunctioningT01-05 IN VIVO CALCIUM IMAGING OF HIPPOCAMPAL CA1 NEURONS REVEALS A FUNCTIONAL INJURY SIGNATURE OF PRIMARY BLAST NEUROTRAUMAHemphill Matthew, Tummala Shanti, Meaney DavidUniversity of Pennsylvania, School of Engineering and Applied Sciences, Philadelphia, USAThe extent of neuronal dysfunction following mild traumatic brain injury (mTBI) is largely unknown, and is a major limitation to the development of treatment strategies. A key unknown is how the neural circuits in brain areas important for cognition change after mTBI, and how these changes affect the neural computations during behavior. Recent reports indicate that the blast overpressure component of an explosion alone can produce some pathology and behavioral deficits common amongst other forms of TBI. We used a miniaturized endoscope implanted in awake behaving mice, in combination with a genetically encoded calcium indicator in the hippocampus, to (1) identify a functional neural circuit ‘signature’ of blast induced TBI (bTBI) and (2) to track the progression of this circuit signature over time after blast exposure to elucidate the trajectory of recovery at the single cell/network level. We transduced CA1 Hippocampal neurons with GCaMP6f, a genetically encoded calcium indicator, and utilized a miniaturized, head-mounted microscope to detect transients of intracellular calcium – serving as a proxy of action potential events - in awake, unconstrained mice. We measured changes in calcium transient morphology from multiple mice (N = 6) and utilized a regression model to identify factors that best distinguished injured and sham groups. We found that changes in variation in magnitude and duration were statistically significant in predicting injured and sham cells. We then scored each cell immediately post blast and tracked its progression at 1 and 5 days. Cells with higher initial scores exhibited larger deviations in Calcium signals at day 5 compared to cells with lower scores, indicating a predictive capacity to identify cells that exhibit sustained responses. These results indicate that primary blast overpressure bTBI alters Calcium signaling at the level of single neurons, with sustained effects of at least 5 days. This platform for tracking the response of individual cells in vivo in time will facilitate the future interrogation of functional recovery and the effects of therapeutic strategies on its trajectory. (Funding Source: MURI W911MF-10-1-0526).Keywords: Blast Induced TBI, in vivo Imaging, Functional Injury, Hippocampus CA1, Calcium Imaging, Mild TBIT01-06 INSIGHTS INTO THE PBTO2 TREATMENT THRESHOLD: EXPLORING A TREATMENT WINDOW SUGGESTED BY ‘BIG DATA’Hirschi Ryan1, Hawryluk Gregory1, Nielson Jessica2, Huie J. Russell2, Zimmermann Lara3, Saigal Rajiv4, Ding Quan5, Ferguson Adam2, Manley Geoffrey21University of Utah, Neurosurgery, Salt Lake City, USA2University of California San Francisco, Neurosurgery, San Francisco, USA3University of California at Davis, Neurosurgery, Sacramento, USA4University of Washington, Neurosurgery, Seattle, USA5University of California at San Francisco, Physiologic Nursing, San Francisco, USABrain tissue hypoxia is common after traumatic brain injury (TBI). Technology exists to detect hypoxia and guide corrective therapy. Current guidelines for the management of severe TBI recommend maintaining PbtO2 > 15–20 mmHg, however uncertainty persists as to the optimal treatment threshold. PbtO2 measures were prospectively and automatically collected every minute from consecutive patients admitted to the San Francisco General Hospital (SFGH) intensive care unit over a 6-year period. We analyzed mean PbtO2 values in TBI patients and the proportion of PbtO2 values below each of 75 thresholds between 0 mmHg to 75 mmHg over various epochs up to 30 days from time of admission. Patient outcomes were calculated using the Glasgow Outcome Scale. We explored putative treatment thresholds by generating 675 separate receiver operator curves (ROC) and 675 generalized linear models (GLM) to examine each 1 mmHg threshold for various epochs. A total of 1,380,841 PbtO2 values were recorded from 190 patients recovering from TBI. A high proportion of PbtO2 measures were below 20 mmHg irrespective of examined epoch. Time below treatment thresholds was more strongly associated with outcome than mean PbtO2. A treatment window was suggested; a threshold of 19 mmHg most robustly distinguished patients by outcome, especially from days 3–5. Benefit to maintaining values at least as high as 33 mmHg was suggested, however. Our “big data” analysis substantially informs the relationship between PbtO2 values and outcome. We were able to discern a therapeutic window for PbtO2 in TBI patients along with minimum and preferred PbtO2 treatment thresholds. Traditional treatment thresholds which have the strongest association with outcome may not be optimal.Keywords: Brain oxygenation, PbtO2, Outcome, Threshold, Treatment windowT01-07 MICROGLIAL INFLAMMASOME ACTIVATION IN PENETRATING BALLISTIC-LIKE BRAIN INJURYLee Stephanie1, Gajavelli Shyam1, Spurlock Markus1, Rivera Karla1, Androni Cody1, de Rivero Vaccari Juan Pablo1, Keane Robert1,2, Bulock Ross1, Dietrich Dalton11Miami Project to Cure Paralysis, Department of Neurological Surgery, Miami, USA2Physiology and Biophysics, University of Miami Miller School of Medicine, Miami, USAPenetrating traumatic brain injury (PTBI) remains a significant cause of death and disability in the United States without effective therapies. A rodent PTBI model, penetrating ballistic-like brain injury (PBBI) has uncovered several secondary pathophysiological mechanisms such as reduced glucose uptake, neurodegeneration, inflammation, and apoptosis that magnify the primary injury. Targeting components of these mechanisms may help improve PTBI outcomes. Activators of innate immunity contribute to secondary injury mechanisms following traumatic brain injury (TBI). Inflammasomes are the key regulators of Il-1β mediated inflammation after TBI and present as clinically relevant targets for therapy. The role of inflammasomes in PBBI pathophysiology has yet to be determined. Towards this, adult male Sprague-Dawley rats were subjected to unilateral sham or PBBI surgery and sacrificed at various time points. Tissues were assessed for expression of cytokines IL-1β, IL-18 and components of the inflammasome, ASC (apoptosis-associated speck like protein containing a caspase activation and recruitment domain), caspase-1, NLRP3 (NOD-like receptor protein 3) and GSDMD (gasdermin-D) by immunoblot analysis and assessed for ASC cell-type expression by immunohistochemistry. Cortical IL-1β and IL-18 expression increased 4 h–48 h and 48 h–72 h, respectively after injury. PBBI also increased caspase-1, ASC, NLRP3, and GSDMD expression from 24 h–48 h. Compared to sham and contralateral cortex, microglial numbers significantly increased 48 h post-injury in the ipsilateral cortex. ASC expression was predominantly increased in activated microglia, permeating the enlarged cell bodies and into the processes. Taken together, this is the first report of inflammasome activation after PBBI and suggests that these activators of inflammation lead to an exacerbation of the pro-inflammatory state post-injury which could underlie the long-term sequlae of PBBI. Inhibition of the inflammasome in PBBI will evaluate its therapeutic potential for PTBI. Supported by NIH NINDS award R01NS089443.Keywords: PBBI, Penetrating Ballistic-like Brain Injury, Inflammasome, Microglia, InflammationT01-08 TEMPORAL PROFILE OF REGIONAL BLOOD-BRAIN BARRIER DISRUPTION IN A MOUSE MODEL OF BLAST-INDUCED MILD TRAUMATIC BRAIN INJURYLogsdon Aric1,2, Meeker Kole1, Bullock Kristin1, Banks William1,2, Cook David1,21Veterans Affairs Puget Sound Health Care System, Geriatric Research Education and Clinical Center, Seattle, USA2University of Washington School of Medicine, Division of Gerontology and Geriatric Medicine Department of Medicine, Seattle, USAA number of groups, including ours, indicate that mild blast-induced traumatic brain injury (mTBI) can cause transient blood-brain barrier (BBB) disruption. Whether short-lived BBB repair processes afford prolonged neuroprotection to mTBI, or can subsequently promote chronic pathologic and functional impairment is not well understood. To begin addressing this issue we mapped the temporal and anatomical profile of BBB disruption following blast exposure. C57/BL6 mice received two consecutive blasts that recapitulate detonation of high explosives in the open field. To assess blast-induced BBB disruption, we co-injected radiolabeled [14C]-sucrose and [99mTc]-albumin, which do not readily cross the intact BBB. We quantified [14C]-sucrose and [99mTc]-albumin in ten brain regions at 0.25, 3, 24, 72, and 168 hours post-blast. A significant increase in [14C]-sucrose was observed in all brain regions, except striatum, at 0.25 h post-mTBI (p < 0.01) compared to sham controls. A similar effect was also observed at 3, 24 and 72 h post-mTBI (p < 0.05). Results suggest an immediate, and sustained BBB opening after mTBI. A significant increase in [99mTc]-albumin was also observed at 0.25 h post-mTBI (p < 0.01), but only in frontal cortex and brain stem. No significant differences in [99mTc]-albumin were found among any brain region at 3 and 24 h post-mTBI. However, a significant increase in BBB disruption was measured in the frontal cortex and brain stem at 72 h post-mTBI (p < 0.05). These results argue that large openings of the BBB are restored within 24 h post-mTBI, followed by a secondary BBB disruption at 72 h. We hypothesize that the secondary BBB opening could be targeted to potentially reduce the chronic pathophysiology associated with neurotrauma.Funding: T32AG05235401 (A.F.L.)Keywords: Blast injury, Blood-brain barrier, Radioactivity, NeuropathologyT01-09 APOLIPOPROTEIN-E4 (APOE4) IMPAIRS BLOOD BRAIN BARRIER FUNCTION AND STABILIZATION FOLLOWING TRAUMATIC BRAIN INJURYMain Bevan, Villapol Sonia, Barton David, Sloley Stephanie, Stefos Kathryn, Burns MarkGeorgetown University, Neuroscience, Washington, USABackground: Blood Brain Barrier (BBB) dysfunction occurs in human TBI patients, yet the molecular mechanisms underlying this pathology remain unclear. The APOE4 gene polymorphism is associated with unfavorable outcomes after TBI including prolonged coma, poor prognosis and enhanced risk of late-onset Alzheimer's disease. Recent evidence implicates APOE in regulating BBB integrity in an isoform dependent manner, via suppression of Cyclophilin A (CypA)–Matrix metallopeptidase-9 (MMP-9) signaling at the Neurovascular Unit (NVU); however, the contribution of apoE to TBI-induced BBB permeability has not been investigated.Methods/Results: Wildtype (C57Bl/6) and humanized APOE3/APOE4 targeted replacement mice were subject to a controlled cortical impact model of TBI, before NVU and BBB permeability responses characterized at 1, 3, 7, and 10 days post-injury. In wildtype mice, an inverse relationship between soluble apoE and BBB permeability is observed, such that BBB permeability decreases as apoE levels increase over time post-TBI (n = 5, **p < 0.01). In APOE3 and APOE4 mice, acute pericyte loss is observed in both genotypes; however, APOE4 mice exhibit delayed pericyte recruitment back to the ipsilateral cortex 7 days post-TBI (n = 4-5, ***p < 0.001). Furthermore, QPCR analysis of microvessels revealed increased MMP9 expression in APOE4 mice at 1, 3 and 7-days post-TBI (n = 5–6, **p < 0.01), in parallel with reduced expression of tight junction proteins Zonula Occludens-1, Occludin and Claudin-5 compared to APOE3 counterparts (n = 5–6, *p < 0.05). Significantly, at 10 days post-injury, BBB leakage remains in APOE4 but not APOE3 mice (n = 4–5, **p < 0.05), suggesting that the E4 isoform impairs BBB stabilization following TBI. This prolonged elevation of BBB permeability in APOE4-TR mice may contribute to deleterious secondary injury processes and indeed T2-weighted MRI shows APOE4 mice have 78% increased lesion volume compared to APOE3-TR mice, 28-days post-injury (n = 8-11, **p < 0.01).Conclusion: These results identify the key role of APOE in mediating BBB permeability and stabilization following TBI. Future studies investigating genotype-specific therapies targeting the BBB may prove beneficial in improving outcomes after TBI.Keywords: Blood Brain Barrier, Apolipoprotein-E4, Neurovascular Unit, Pericyte signaling, BBB permeability and stabilizationT01-10 THE STEALTH PATHOLOGIES OF MILD TBI AND DEMONSTRATION THAT ADVANCED NEUROIMAGING MAY NOT BE AS SENSITIVE AS ADVERTISEDMallela Arka, Swanson Randel, Johnson Victoria, Parker Andrew, Elliott Mark, Weber Maura, Acharya Nimish, Cognetti John, Cullen Kacy, Verma Ragini, Smith DouglasUniversity of Pennsylvania, Department of Neurosurgery, Philadelphia, USABackground: Diffuse axonal injury (DAI), a signature injury of mild TBI (mTBI), is a ‘stealth’ pathology, invisible on conventional neuroimaging. Diffusion tensor imaging (DTI) has been used to identify DAI in clinical populations. However, studies demonstrate conflicting changes such as increases, decreases, or no change in fractional anisotropy (FA) or mean diffusivity (MD) following injury. Multiple pathologies, including axonal injury, BBB disruption, or ionic/fluid shifts, can change diffusion properties. Further validation in preclinical models is required.Objectives: To determine if diffusion imaging can identify histologic axonal injury in a translational, clinically-relevant, closed-head rotational injury model.Methods: Nine female swine underwent closed-head rotational injury. Animals were imaged before and 72 h following injury. Amyloid precursor protein (APP) IHC was performed to identify damaged axonal profiles. The change in diffusion metric (FA, MD) and number of APP(+) axonal profiles was correlated across all WM and in specific tracts-internal capsule (IC), fornix, corpus callosum, etc.Results: Mean FA/MD was not significantly different after injury in any tract (p > 0.05) despite the presence of APP(+) profiles. However, the proportion of voxels with high FA was significantly lower post-injury in the L, R fornix and R IC (p < 0.05). The change in proportion correlated with the number of APP(+) axons (p < 0.05). In whole brain analysis, in voxels with APP(+) axons, the degree of APP pathology correlated with diffusion change (p < 0.05). However, diffusion changes were also observed in voxels not containing APP(+) axons.Conclusion: Based of this preliminary translational study, changes in DTI metrics may be sensitive but not specific to histologic axonal injury. Averaging metrics along tracts may average out diffuse/multifocal changes, so changes along each tract must be analyzed. Further comparison of diffusion imaging and other pathologies and clinical correlation in larger human studies is required.Support: Supported by DOD grant, PT110785 and NIH grants, NS38104, NS092389 and EB021293Keywords: Mild TBI, Concussion, Neuroimaging, Diffuse Axonal InjuryT01-11 CANNABIDIOL ADMINISTRATION AFTER SPINAL CORD INJURY REDUCES ALLODYNIA IN MALE AND FEMALE RATS, WITH MOST ROBUST EFFECTS IN FEMALESMohaimany-Aponte Amanda1, Pat Betty1, McAllister Sean2, Floyd Candace11University of Alabama at Birmingham, Physical Medicine and Rehabilitation, Birmingham, USA2California Pacific Medical Center Research Institute, San Fransisco, USAOver 60% of persons with spinal cord injury (SCI) experience neuropathic pain (SCI-NP), which frequently is listed as a top concern due to few treatment options. Clinically, cannabidiol (CBD), a non-psychotropic constituent of Cannabis sativa, has shown efficacy in treating some chronic pain disorders. However, effectiveness of CBD in treating SCI-NP has not been examined. The central hypothesis of this study is that acute post-SCI administration of CBD will ameliorate SCI-NP development and that these effects are sexually dimorphic. We recorded baseline motor and sensory function measures from adult male and female Sprague Dawley rats. Rats then received either laminectomy or SCI with the SCI groups receiving a unilateral 300 kdyne impact at the 5th cervical level. SCI groups where randomized to receive vehicle or CBD (100 mg/kg) beginning 30 minutes post-SCI, then once daily for 7 consecutive days. Weekly assessments of motor and sensory function were taken for 6 weeks. We found SCI reduced motor function in both sexes and CBD treatment conferred modest improvement in motor function in females. Regarding sensory tests, SCI induced an increase in sensitivity to mechanical stimuli in males and CBD reduced this tactile allodynia in males. Robust cold allodynia was observed in both sexes after SCI and CBD reduced development of cold allodynia in both males and females, with more pronounced reduction in females. Additionally, over-grooming of the affected hindpaw was observed in both sexes following SCI and the percentage of rats exhibiting over-grooming was reduced in CBD treated males and females. In conclusion, CBD administration post-SCI conferred modest reduction in motor deficits in females and significant effects in ameliorating cold allodynia and over-grooming in both sexes, with more robust effects in females. Support: UAB TJ Atchinson SCI Research Program and Conquer Paralysis Now Grant (CF, SM).Keywords: spinal cord injury, neuropathic pain, cannabidiolT01-12 REBALANCING OF BRAIN CIRCUITS BY TEMPORARY CORTICAL SILENCING SHOWS POST-INJURY TEMPORAL DEPENDENCE AFTER RAT TBIPaydar Afshin, Harris Neil G.UCLA, Neurosurgery, Brain Injury Research Center, Los Angeles, USAWe have previously shown that the injured brain is both functionally disconnected as well as hyperconnected, and in a region-dependent manner after controlled cortical impact (CCI) injury in the adult rat. Our recent data shows that remote, homotopic cortical regions become hyperexcitable with time post-injury, and we hypothesized that this results in increased trans-hemispheric cortical inhibition, preventing reorganization of the primary injured hemisphere. In support of this, other data from our lab show that temporary silencing the contralesional sensorimotor cortex at 1wk after CCI injury normalizes affected forelimb use, but not when conducted at 4 wks. To determine whether this occurs due to restoration of the afferent pathway connectivity, or to reorganization of brain-centric circuits, we acquired forelimb-evoked-fMRI and resting state fMRI data at 1 and 4 wks post-injury after contralateral silencing with intraparenchymal injection of muscimol, and compared data to a vehicle-injected-injured (n = 9 vs 3) as well as sham rats (n = 3). Data were analyzed by statistical parametric mapping for the forelimb-evoked cortical map, and by graph theory for network-based functional connectivity (fc). As predicted, contralesional silencing at 1wk and 4 wks post-injury decimated the unaffected-limb-evoked contralesional cortical map, compared to vehicle-injected (P < 0.05, z = 1.7 cluster-corrected), but this did not restore the affected-limb-evoked cortical map to the ipsilesional hemisphere at either post-injury time-points. However, contrary to this, while fc analysis also demonstrated that silencing led to the expected contralateral cortical disconnection (reduction in str