OBJECTIVE:. To assess physician acceptance of a Virtual Reality Brain Death Determination Tool (VRBDDT) as an educational modality and its impact on physician knowledge and confidence in brain death determination and communication with patient families. DESIGN:. Prospective pilot study using surveys administered pretraining and post-training. SETTING:. One hundred twenty-six acute care hospitals within the Gift of Life Donor Program’s Donor Service Area. SUBJECTS:. Physicians responsible for performing brain death determination. INTERVENTIONS:. Participants completed a novel, virtual reality-based training program consisting of eLearning modules integrated with virtual reality simulations of brain death determination procedures and family communication. MEASUREMENTS AND MAIN RESULTS:. Of 142 enrolled participants, 69 completed both pretraining and post-training assessments consisting of a 14-item questionnaire. Median scores significantly improved from 73.2% pretraining to 91.1% post-training (p < 0.001). Participants demonstrated the largest improvements in knowledge about clinical examination procedures and family communication skills. Self-reported confidence significantly increased post-training, with high satisfaction and acceptance ratings reported by participants. CONCLUSIONS:. The VRBDDT was accepted by physicians and significantly enhanced knowledge and confidence related to brain death determination and family communication.

When patients suffer from a disorder of consciousness, surrogate decision makers commonly express hope for a miracle, a potential source of moral distress for neurologists. Fischer et al. apply a systematic framework for neuroprognostication to understand, delineate, and appropriately respond to distinct types of miracles.

INTRODUCTION:Coagulopathy in the setting of traumatic brain injury (TBI) increases the risk of poor outcomes. Thromboelastography with platelet mapping (TEG-PM) provides a dynamic assessment of clotting parameters including adenosine diphosphate (ADP) inhibition and can guide antiplatelet reversal. METHODS:A cross-sectional study of a single Level I Trauma Center traumatic brain injury database from February 2015 to March 2024 was conducted to develop a prediction model of ADP inhibition. Included patients had evidence of traumatic intracranial hemorrhage on CT at the time of presentation and underwent TEG-PM testing. Patients with a history of antiplatelet or anticoagulant use were excluded. Significant ADP inhibition was defined as ≥ 60%. RESULTS:485 patients were included. Patients with significant ADP inhibition were younger and more likely to have a severe head injury (Glasgow Coma Scale 3-8). In a multivariate logistic regression model including age and head injury severity as independent variables, severe head injury significantly increased the likelihood of ADP inhibition (odds ratio 2.14, 95% confidence interval 1.28-3.58). CONCLUSION:The observation that severe head injury was significantly associated with ADP inhibition could help identify patients at risk for platelet dysfunction in settings without TEG-PM.

Caring for patients with a terminal prognosis after a non-survivable head injury is fraught with ethical and moral challenges. A web-based, 25-question survey was distributed to fifty academic hospitals. Conventional descriptive statistics and inferential analyses were employed. 133 physicians completed the survey (29% neurosurgery, 25% trauma surgery, 45% critical care). Medical literacy (25%), patient religious/moral views (23%) and trust (17%) were identified as the most significant communication barriers. When broadly asked what outside forces influenced what interventions were offered, physicians cited organ procurement organizations (OPO; 12%) and medical malpractice concerns (10%). Critical care physicians (73.3%) and trauma surgeons (73.5%) were more likely to provide further life-prolonging care to patients with an unknown organ donor status than neurosurgeons (48.7%, p value = 0.023). However, no significant difference was observed between specialties when considering non-organ donors (neurosurgery = 61.5%, critical care = 50%, trauma surgery = 58.5%, p value = 0.481). Physicians reported that disclosing non-survivability to families (43%) and providing futile care (61%) were detrimental to their own mental health. However, 60% percent of respondents felt fulfilled by caring for patients and families after this type of injury. Overall, our findings show variation in how physicians manage patients after non-survivable head trauma. Clear guidelines delineating reasonable and futile interventions would allow for standardization of care and opportunity for organ donation where appropriate. Additionally, this study revealed a potential impact of non-medical influences such as organ-procurement organizations and medicolegal fears when determining interventions offered. While this study shows that the burden of communicating with families and providing futile medical care takes a toll on mental health to providers, many clinicians continue to derive meaning from their role in the care of these patients.

Introduction:Neuroprognostication for disorders of consciousness, particularly after cardiac arrest, is critical. However rapidly evolving research has translated little to clinical practice, with neuroprognostication frequently deviating from evidence and clinical guidelines. We implemented a novel program that provides specialized, interdisciplinary, and longitudinal care to improve the practice of neuroprognostication. The objective of this study was to evaluate the impact of this program on provider attitudes and satisfaction towards neuroprognostication after cardiac arrest. Methods:We disseminated surveys across our health system to critical care providers and neurologists in the years before (2021, 2022) and after (2023) implementation of the program. The surveys assessed perceptions of, and satisfaction with, neuroprognostication after cardiac arrest. We used Fisher exact tests to compare program-exposed respondents to historical controls (2021 and 2022 respondents) and contemporary controls (2023 respondents without program exposure). Results:We received 545 responses from neurologists and critical care providers, including nurses, trainees, and attendings. Program-exposed respondents, relative to historical and contemporary controls respectively, reported greater usefulness of neuroprognostication (94% reporting often or always useful, versus 69% [p < 0.01]) and 68% [p < 0.01]), comprehensiveness of neuroprognostication (94% reporting often or always comprehensive, versus 76% [p = 0.02] and 66% [p < 0.01]), and greater satisfaction with neuroprognostication, particularly in comparison to the conventional model (63% reporting the program was "much better"). Conclusion:Implementation of a specialized neuroprognostication program was associated with largely favorable attitudes towards neuroprognostication among providers. These findings encourage further study of this paradigm, and consideration of broader adoption to improve the practice of neuroprognostication.

Background:The effect of different thresholds for packed red blood cell transfusion on neurologic outcomes in patients with subarachnoid hemorrhage and anemia is uncertain. This meta-analysis aimed to evaluate the effect of liberal versus restrictive transfusion strategies on functional outcomes in subarachnoid hemorrhage. Methods:We systematically searched MEDLINE (inception-March 26, 2025) for randomized controlled trials comparing functional neurological outcomes in adults with aneurysmal subarachnoid hemorrhage assigned to receive packed red blood cell transfusion using high versus low hemoglobin thresholds. Risk of bias was assessed using Cochrane Risk of Bias tool 2.0. Unfavorable neurologic outcomes were defined based on trial-specific primary neurologic outcome definitions (Glasgow Outcome Scale Extended score ≤5 or modified Rankin Scale score ≥3 or modified Rankin Scale score ≥4). An exploratory analysis using Glasgow Outcome Scale Extended score ≤5 or modified Rankin Scale score ≥3 as unfavorable neurologic outcome was also performed. We calculated the pooled risk ratio (RR) with 95% CI for unfavorable neurologic outcome using random effect models and assessed heterogeneity using Cochran's Q test. Results:Of 1628 studies, 3 trials (n = 953 patients) met the inclusion criteria. Over a follow-up of 3-12 months, 181/470 patients (38.5%) randomized to liberal transfusion strategies (hemoglobin<9-11.5g/dL) compared with 214/483 patients (44.3%) in the restrictive strategy group (hemoglobin<7-10g/dL) experienced unfavorable neurologic outcomes. Liberal (versus restrictive) packed red blood cell transfusion strategies resulted in a nonsignificant reduction (RR, 0.88; 95% CI, 0.77-1.01; P = 0.06; I2 = 0%) in unfavorable neurologic outcomes per trial-specific definitions and RR = 0.89 (95% CI, 0.79-0.99; P = 0.04; I2 = 0%) when unfavorable outcome was defined as Glasgow Outcome Scale Extended score ≤5 or modified Rankin Scale score ≥3. Sensitivity analysis, excluding the small pilot trial (n = 44) with a higher hemoglobin threshold, did not change the summary effect. Conclusions:Our study demonstrated a trend toward better neurologic outcomes with liberal transfusion strategies in patients with subarachnoid hemorrhage. Further studies are required to determine the optimal transfusion strategy for this high-risk population and identify subgroups that are most likely to benefit from the liberal strategy.

In the United States (US), hypertension is more prevalent among certain ethnic and racial groups including: Black-African Americans (BAA), Hispanics, American Indian and Alaska Native (AI/AN) and Asian and Pacific Islander (API); these populations also experience higher hypertension- and stroke-related mortality rates among both non-pregnant and pregnant adults compared to non-Hispanic White (NHW) Americans. The causes for the increased prevalence and higher case-fatality rate are unclear; however, social determinants of health (SDoH) and systemic racism likely play significant roles. While genetic factors may contribute to hypertension, no definitive genetic variations have been identified. Candidate traits show only inconclusive links to the disproportionate burden of hypertension among BAA. Socio-economic factors, environmental factors, and other SDoH likely drive the observed higher rates of hypertension and stroke morbidity in BAA and other ethnic groups. Hypertensive disorders are a leading cause of maternal mortality disproportinately affecting BAA women. Studies estimate that up to one-third of disparities in hypertension management in the US can be attributed to SDoH. Healthcare disparities in obstetric patients with stroke are similar to those among non-childbearing adults; however, notable differences include access to prenatal care and parental factors. Despite advances in medical treatments, improved patient education and substantial healthcare spending, maternal mortality and morbidity rates have risen in recent years. The impact of the disparities, in the case of obstetric patients, may also affect fetal development and subsequent neonatal and pediatric health. Racial and ethnic minorities in the US, namely BAA and Hispanics, AI/AN and API, continue to experience disparities in the incidence, prevalence, and treatment of hypertension and stroke. Factors such as socioeconomic status, structural racism and healthcare access affect hypertension prevalence and outcomes, as may noise pollution, sleep hygiene, air quality and other environmental factors. In pregnant women, these disparities have a negative impact on mortality rates and stroke risk. Despite ongoing research, racial and ethnic minorities remain underrepresented in clinical studies, underscoring the need for more inclusive research to improve hypertension management in diverse populations.

Abstract Arterial thrombosis, venous thromboembolism, and intracranial bleeding are commonly encountered in neurologically injured patients. Inherited and acquired thrombophilias and cancer-related thrombosis are common causes of ischaemic stroke, cerebral venous sinus thrombosis, and venous thromboembolism. Factor deficiencies and acquired thrombocytopenias may lead to brain haemorrhages that cause permanent disability or death. Treatment of these cerebrovascular injuries is remarkably time-sensitive and the window of opportunity to intervene is small. Treatment of arterial thrombosis, such as in myocardial infarction and stroke, differs from that of venous thromboses such as deep venous thrombosis (DVT) and pulmonary embolism (PE). Deficiencies of natural anticoagulant proteins or gene mutations in procoagulant factors are rare; however, they are strong risk factors for venous thromboembolism (VTE), especially in the young or those with a positive family history. Inherited thrombophilias include deficiencies of the natural anticoagulant proteins antithrombin (AT), protein C (PC), and protein S (PS), as well as the gain-of-function mutations in the factor V gene (factor V Leiden (FVL)) and prothrombin gene (PT G20210A). Thrombocytopenia can be a result of impaired platelet production and bone marrow suppression, blood loss with inadequate bone marrow response, extravascular sequestration, or extracorporeal destruction (splenomegaly, dialysis), as well as intravascular consumption. For patients with acute ischaemic stroke from suspected thrombophilia, common questions relate to the choice of antithrombotic therapy, potential endovascular interventions, and the extent of diagnostic evaluation. For management of life-threatening intracranial bleeding complications, knowledge of factor replacement strategies, reversal agents, and dosing protocols are critical to achieving haemostasis and optimizing neurological outcomes. This chapter reviews neurological complications and treatment of commonly encountered coagulation disorders such as genetic haemophilias, inherited and acquired thrombocytopenias, inherited and acquired thrombophilias, and manifestations of cancer-related hypercoagulability.

OBJECTIVE:Among patients with large vessel occlusion (LVO) and large ischemic cores, critical decisions often need to be made about decompressive hemicraniectomy (DHC) or early withdrawal of life-sustaining therapy (WLST). In this study, we aimed to evaluate utilization of DHC and early WLST and factors associated with them in patients with large strokes from the SELECT2 trial. METHODS:We analyzed the entire SELECT2 trial population, which randomized 352 patients with stroke due to LVO and large ischemic cores to endovascular thrombectomy (EVT) or medical management. We used the as-treated principle to compare the use of DHC and early WLST within 7 days after randomization. We further assessed functional outcomes (modified Rankin Score) after these decisions. RESULTS:Of 352 patients enrolled in this study, 55 received DHC and 81 transitioned to early WLST. Patients treated with EVT were as likely to undergo DHC (16% vs 15%, adjusted relative risk [aRR] = 1.19, 95% CI:0.75-1.88, p = 0.46) or WLST (22% vs 24%, aRR = 0.94, 95% CI: 0.66-1.34, p = 0.72) as those given medical management. DHC was used more frequently in younger patients and WLST more in older patients. EVT efficacy was maintained after adjusting for DHC (adjusted generalized odds ratio [aGenOR] = 1.68, 95% CI: 1.24-2.11, p < 0.001), with no interaction between DHC and treatment (p-interaction = 0.93). At 1 year, 21% of DHC-treated patients were ambulatory; the outcomes were universally poor after early WLST. INTERPRETATION:In the SELECT2 trial of patients with large ischemic core, DHC was performed in ~1 of 6 patients and early WLST in ~1 of 5 patients, without differences based on treatment with EVT or medical management, nor successful reperfusion. DHC or WLST did not detract from thrombectomy treatment benefit. Additionally, ~20% of patients achieved independent ambulation despite receiving DHC by the 1-year follow-up. The similar distribution of these critical care decisions provides reassurance that the overall trial outcomes were not biased by open-label treatment allocation. ANN NEUROL 2025;97:698-708.

Mobilization in the Neurological Intensive Care Unit (NICU) significantly improves outcomes and functional recovery while preventing immobility-related complications. The heterogeneity of neurologic conditions necessitates tailored, interdisciplinary mobilization strategies. This article reviews recent research on enhancing the feasibility and effectiveness of mobilization interventions in NICU settings. Early mobilization improves functional outcomes, reduces complications like muscle atrophy and pressure ulcers, and can shorten ICU stays. Safe implementation involves individualized protocols and a multidisciplinary team, emphasizing that early mobilization benefits critically ill neurological patients. Development of evidenced-based protocols for interdisciplinary NICU patient mobilization enhances patient outcomes and quality of life. Use of outcome measures can facilitate mobility while preventing complications from immobility. Future research in embracing emerging technologies such as mobilization equipment and virtual/augmented reality will help determine optimal timing as well as dosage of mobility to improve long-term functional outcomes in the unique NICU population.

AbstractIntroductionThe rapid adoption of electronic health record (EHR) systems has resulted in extensive archives of data relevant to clinical research, hospital operations, and the development of learning health systems. However, EHR data are not frequently available, cleaned, standardized, validated, and ready for use by stakeholders. We describe an in‐progress effort to overcome these challenges with cooperative, systematic data extraction and validation.MethodsA multi‐disciplinary team of investigators collaborated to create the Complete Inpatient Record Using Comprehensive Electronic Data (CIRCE) Project dataset, which captures EHR data from six hospitals within the University of Pennsylvania Health System. Analysts and clinical researchers jointly iteratively reviewed SQL queries and their output to validate desired data elements. Data from patients aged ≥18 years with at least one encounter at an acute care hospital or hospice occurring since 7/1/2017 were included. The CIRCE Project includes three layers: (1) raw data comprised of direct SQL query output, (2) cleaned data with errors removed, and (3) transformed data with standardized implementations of commonly used case definitions and clinical scores.ResultsBetween July 1, 2017 and December 31, 2023, the dataset captured 1 629 920 encounters from 740 035 patients. Most encounters were emergency department only visits (n = 965 834, 59.3%), followed by inpatient admissions without an intensive care unit admission (n = 518 367, 23.7%). The median age was 46.9 years (25th–75th percentiles = 31.1–64.7) at the time of the first encounter. Most patients were female (n = 418 303, 56.5%), a significant proportion were of non‐White race (n = 272 018, 36.8%), and 54 625 (7.4%) were of Hispanic/Latino ethnicity.ConclusionsThe CIRCE Project represents a novel cooperative research model to capture clinically validated EHR data from a large diverse academic health system in the greater Philadelphia region and is designed to facilitate collaboration and data sharing to support learning health system activities. Ultimately, these data will be de‐identified and converted to a publicly available resource.

Introduction and Problem Statement:Neurocritical care (NCC) is a niche clinical subspecialty dependent on interdisciplinary cohesion to operate in critical situations. Team cohesion in an intensive care unit (ICU) depends not only on technical skills or medical knowledge but also on nontechnical skills such as teamwork, communication, and leadership. Developing and practicing these skills as an interdisciplinary team is not standard in most professional training programs. Objectives:This project aimed to (1) design and implement a NCC in situ simulation program aimed at practicing teamwork, (2) demonstrate feasibility and acceptability of recurring in situ simulations, and (3) assess baseline teamwork scores and clinician preparedness to respond to a clinical emergency. Methods and Curriculum Description:The NLN Jeffries Simulation Theory was used to guide the simulation program design. A 1-year pilot project consisted of monthly NCC in situ simulations. Debriefing with Good Judgment was used to guide postsimulation reflection. Feasibility was evaluated by participation metrics and simulation schedule adherence. Acceptability was assessed through postsimulation evaluations. Teamwork and preparedness were measured using the Mayo High Performance Teamwork Scale (MHPTS) and 10-point Likert scale, respectively. Statistical comparison of MHPTS scores between disciplines and preparedness before vs after simulation was conducted. Results and Assessment Data:In 1 year, we conducted 12 in situ simulations, with 167 simulation learner encounters, representing 95 unique learners and 72% of our core NCC team (i.e., nurses, advanced practice providers [APPs], fellows, faculty). Analysis of program evaluations (84% survey completion rate) showed that 91% of all learners strongly agreed that the simulation provided an experiential, collaborative, trusting, and learner-centered environment. Overall, MHPTS scores were similar between disciplines, although in pairwise comparison, pharmacists rated teamwork significantly lower than both nurses (p = 0.01) and APPs (p = 0.004). Learners rated their preparedness to respond to a clinical emergency significantly higher after the simulation (p < 0.001). Discussion and Lessons Learned:In situ simulation training is a feasible and acceptable method to introduce teamwork training into ICU culture. Team-based simulation improves self-reported preparation to respond to clinical emergencies. Simulation training that takes place in the clinical setting provides a powerful tool for enhancing teaching and addressing patient care gaps.

Purpose of Review Bed rest was a treatment recommended for critically ill patients admitted to the intensive care unit (ICU) that aimed to minimize energy expenditure, permit wound healing and minimize somatic stressors. However, evidence demonstrates that bed rest leads to disuse atrophy, which may be compounded by premorbid sarcopenia and ICU-acquired weakness (ICUAW). ICUAW partly results from muscle breakdown and systemic inflammation and may exacerbate critical illness. Coupled with analgosedation, ICUAW may prolong mechanical ventilation (Kho et al. in BMJ Open Respir Res. 2019;6(1) 2019 ; Maffei et al. in Arch Phys Med Rehabil. 2017;98 2017 ; McWilliams et al. in J Crit Care. 2018;44 2018 ; Sarfati et al. in J Crit Care. 2018;46 2018 ), increase risk of venous thromboembolism (Denehy et al. in Intensive Care Med. 2017;43(1) 2017 ; Lyles in J Am Geriatr Soc. 1988;36(11) 1988 ) create dependence on vasopressor agents (Lyles in J Am Geriatr Soc. 1988;36(11) 1988 ; Fortney et al. in Comprehen Physiol. 1996 ) restrict joint mobility, and induce pressure injuries. Neurologically injured patients may be at a higher risk of ICUAW than other critically-ill patients, given that neurological injury itself results in weakness, which may be focal or generalized. Early mobilization (EM), typically defined as physical therapy within 72 h of ICU (Cumming et al. in Neurology. 2019;93(7) 2019 ), may preempt or mitigate these deleterious consequences of critical care. Recent Findings Retrospective data suggest that EM protocols reduce ventilator days, decrease venous thromboembolism, avert pressure wounds, and reduce the length of stay. EM may reduce the incidence, duration, and severity of delirium (Morris et al. in Crit Care Med. 2008;36(8) 2008 ; Needham et al. in Arch Phys Med Rehabil. 2010;91(4) 2010 ). Larger and more rigorous studies have not demonstrated benefit of EM on outcomes after critical care; some have demonstrated harm. Neurologically injured critical care patients have generally been excluded from early mobilization protocols due to safety concerns that stem from the increased potential for falls, disorders of consciousness, cognitive impairment, intracranial hypertension, and potential dislodgment of intracranial devices. Notably, data from patients with ischemic stroke suggest that EM may also be associated with harm in this group. Summary EM may benefit neurologically injured patients once acute ischemia, elevated ICP, and seizures are resolved. Targeting moderate acuity patients may be critical to improving outcomes and optimizing resource utilization in this resource-intensive intervention. The duration of mobility session, optimal frequency of mobility session, and timing of session remain to be determined.

Background:The optimal time to restart direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF) after traumatic intracranial hemorrhage (tICH) is unknown. Physicians must weigh the risk of recurrent hemorrhage against ischemic stroke. We investigated rates of stroke while holding anticoagulation, hemorrhage after anticoagulation resumption, and factors associated with the decision to restart anticoagulation.Methods:Patients presenting to our level I trauma center for tICH while on a DOAC for NVAF were retrospectively reviewed over 2 years. Age, sex, DOAC use, antiplatelet use, congestive heart failure, hypertension, age, diabetes, previous stroke, vascular disease, sex score for stroke risk in NVAF, injury mechanism, bleeding pattern, Injury Severity Score, use of a reversal agent, Glasgow Coma Scale at 24 hours, hemorrhage expansion, neurosurgical intervention, Morse Fall Risk, DOAC restart date, rebleed events, and ischemic stroke were recorded to study rates of recurrent hemorrhage and stroke, and factors that influenced the decision to restart anticoagulation.Results:Twenty-eight patients sustained tICH while on a DOAC. Fall was the most common mechanism (89.3%), and subdural hematoma was the predominant bleeding pattern (60.7%). Of the 25 surviving patients, 16 patients (64%) restarted a DOAC a median 29.5 days after tICH. One patient had recurrent hemorrhage after resuming anticoagulation. One patient had an embolic stroke after 118 days off anticoagulation. Age >80, Injury Severity Score ≥16, and expansion of tICH influenced the decision to indefinitely hold anticoagulation.Conclusion:The low stroke rate observed in this study suggests that holding DOACs for NVAF for 1 month is sufficient to reduce the risk of stroke after tICH. Additional data are required to determine optimal restart timing.

Prediction of neurological clinical outcome after acute brain injury is critical because it helps guide discussions with patients and families and informs treatment plans and allocation of resources. Numerous clinical grading scales have been published that aim to support prognostication after acute brain injury. However, the development and validation of clinical scales lack a standardized approach. This in turn makes it difficult for clinicians to rely on prognostic grading scales and to integrate them into clinical practice. In this review, we discuss quality measures of score development and validation and summarize available scales to prognosticate outcomes after acute brain injury. These include scales developed for patients with coma, cardiac arrest, ischemic stroke, nontraumatic intracerebral hemorrhage, subarachnoid hemorrhage, and traumatic brain injury; for each scale, we discuss available validation studies.

Traumatic intracranial hemorrhages expand in one third of cases, and antiplatelet medications may exacerbate hematoma expansion. However, the reversal of an antiplatelet effect with platelet transfusion has been associated with harm. We sought to determine whether a thromboelastography platelet mapping (TEG-PM)-guided algorithm could limit platelet transfusion in patients with hemorrhagic traumatic brain injury (TBI) prescribed antiplatelet medications without a resultant clinically significant increase in hemorrhage volume, late hemostatic treatments, or delayed operative intervention. A total of 175 consecutive patients with TBI were admitted to our university-affiliated, level I trauma center between March 2016 and December 2019: 54 preintervention patients (control) and 121 patients with TEG-PM (study). After exclusion for anticoagulant administration, availability of neuroimaging and emergent neurosurgery, 62 study patients and 37 control patients remained. Intervention consisted of administration of desmopressin (DDAVP) for nonsurgical patients with significant inhibition at the arachidonic acid or adenosine diphosphate receptor sites. For surgical patients with significant inhibition, dual therapy with DDAVP and platelet transfusion was employed. Study patients were compared with a group of historical controls, which were identified from a prospectively maintained registry and typically treated with empiric platelet transfusion. Median age was 75 years (interquartile range 85–67) and 77 years (interquartile range 81–65) in the TEG-PM and control patient groups, respectively. Admission hemorrhage volumes were similar (10.7 cm3 [20.1] in patients with TEG-PM vs. 14.1 cm3 [19.7] in controls; p = 0.41). There were no significant differences in admission Glasgow Coma Scale, mechanism of trauma, or baseline comorbidities. A total of 57

INTRODUCTION:Beta-blockers (BB) after traumatic brain injury (TBI) accelerate cognitive recovery weeks after injury. BBs also inhibit leukocyte (LEU) mobilization to the penumbral blood brain barrier (BBB) 48-h after TBI. It is unclear whether the latter effects persist longer and accompany the persistent cognitive improvement. We hypothesized that 2 wk of BB after TBI reduce penumbral BBB leukocyte-endothelial interactions. METHODS:Thirty CD1 mice underwent TBI (controlled cortical impact, CCI: 6 m/s velocity, 1 mm depth, 3 mm diameter) or sham craniotomy followed by i.p. saline (NS) or propranolol (1, 2, 4 mg/kg) every 12 h for 14 d. On day 14, in vivo pial intravital microscopy visualized endothelial-LEU interactions and BBB microvascular leakage. Day 14 Garcia neurological test scores and animal weights were compared to preinjury levels reflecting concurrent clinical recovery. RESULTS:LEU rolling was greatest in CCI + NS when compared to sham (P = 0.03). 4 mg/kg propranolol significantly reduced postCCI LEU rolling down to uninjured sham levels (P = 0.03). LEU adhesion and microvascular permeability were not impacted at this time interval. Untreated injured animals (CCI + NS) scored lower Garcia neurological test and greater weight loss recovery at day 14 when compared to preinjury (P < 0.05). Treatment with higher doses of propranolol (2, 4 mg/kg), improved weight loss recovery (P < 0.001). CONCLUSIONS:LEU rolling alone, was influenced by BB therapy 14 d after TBI suggesting that certain penumbral neuroinflammatory cellular effects of BB therapy after TBI persist up to 2 wk after injury potentially explaining the pervasive beneficial effects of BBs on learning and memory.