Clinical Outcomes of Anticoagulated Patients With Atrial Fibrillation After Falls or Head Injury: Insights From RE-LY.

BACKGROUND: Falls are always a concern regarding the balance of risk/benefit in patients with atrial fibrillation treated with anticoagulants. In this analysis, we aimed to evaluate the outcomes of patients that had a fall/head injury reported in the RE-LY clinical trial (Randomized Evaluation of Long-Term Anticoagulation Therapy) and to explore the safety of dabigatran (a nonvitamin K antagonist oral anticoagulant). METHODS: We performed a post hoc retrospective analysis of intracranial hemorrhage and major bleeding outcomes in the RE-LY trial with 18 113 individuals with atrial fibrillation, according to the status occurrence of falls (or head injury) reported as adverse events. Multivariate Cox regression models were used to provide adjusted hazard ratio (HR) and 95% CI. RESULTS: In the study, 974 falls or head injury events were reported among 716 patients (4%). These patients were older and had more frequently comorbidities such as diabetes, previous stroke, or coronary artery disease. Patients with fall had a higher risk of major bleeding (HR, 2.41 [95% CI, 1.90-3.05]), intracranial hemorrhage (HR, 1.69 [95% CI, 1.35-2.13]), and mortality (HR, 3.91 [95% CI, 2.51-6.10]) compared to those who did not have reported falls or head injury. Among patients who had falls, those allocated to dabigatran showed a lower intracranial hemorrhage risk (HR, 0.42 [95% CI, 0.18-0.98]) compared with warfarin. CONCLUSIONS: In this population, the risk of falls is important and confers a worse prognosis, increasing intracranial hemorrhage, and major bleeding. Patients who fell and were under dabigatran was associated with lower intracranial hemorrhage risk than those anticoagulated with warfarin, but the analysis was merely exploratory.

[Application Effect of Continuous Lumbar Cistern Fluid Drainage Combined With Decompressive Craniectomy in the Treatment of Severe Craniocerebral Injury].

Objective: To analyze the application effect of continuous lumbar cistern fluid drainage combined with decompressive craniectomy in the treatment of severe craniocerebral injury. Methods: A total of 87 patients with severe craniocerebral injury admitted to our hospital between March 2016 and March 2021 were retrospectively enrolled. They were divided into two groups according to the decompression methods applied, with 42 patients who received standard decompressive craniectomy assigned to the control group and 45 patients who received continuous lumbar cistern fluid drainage combined with standard decompressive craniectomy assigned to the observation group. The primary indicators that were monitored and compared between the two group included the amount of time for patient CT imaging to be clear of subarachnoid hemorrhage, the length-of-stay, the duration of post-operative intubation, the mannitol dose, scores for Glasgow Coma Scale (GCS), prognosis, the incidence of cerebral edema and cerebral infarction, and complications. The secondary indicators that were monitored and compared included intracranial pressure, cerebrospinal fluid antinucleosome protein SP100, and red blood cell count of the two groups before treatment and after continuous drainage for 7 days. Results: The amount of time for CT imaging to be clear of subarachnoid hemorrhage and the length-of-stay of the observation group were shorter than those of the control group, the mannitol dose of the observation group was lower than that of the control group, the incidence of cerebral edema and the incidence of complications of the observation group were lower than those of the control group, and the rate of patients with good prognosis in the observation group was higher than that in the control group ( P<0.05). There was no significant difference in the rate of poor prognosis or mortality between the two groups ( P>0.05). The duration of postoperative intubation of the observation group was (8.24±1.09) d, while that of the control group was (9.22±1.26) d, and the difference between the two groups was statistically significant ( t=3.887, P<0.05). There were 2 cases (4.44%) of cerebral infarction in the observation group, with the infarct volume being (8.36±1.87) cm 3, while there were 9 cases (21.43%) of cerebral infarction in the control group, with the infarct volume being (8.36±1.87) cm 3, and there were statistically significant differences in the incidence and volume of cerebral infarction between the two groups ( χ 2=5.674, t=9.609, P<0.05). After treatment, the intracranial pressure and red blood cell count decreased in both groups and the intracranial pressure, cerebrospinal fluid SP100, and red blood cell count of the observation group were significantly lower than those of the control group ( P<0.05). The cerebrospinal fluid SP100 of the observation group decreased after treatment in comparison with the level before treatment ( P<0.05), while the pre- and post-treatment levels of the control group did not demonstrate any significant difference. Conclusion: Continuous lumbar cistern fluid drainage in patients with severe craniocerebral injury effectively shortens the time required for the body to recover, significantly reduces the level of intracranial pressure, improves the levels of cerebral edema and cerebral infarction, and has a high degree of safety for prognosis and recovery.

Study of Compound Sanqi Nanoparticles for Local Infection of Hydrocephalus Patients after Neurosurgery Medium Craniocerebral Injury.

Panax notoginseng is the dried root and rhizome of Panax notoginseng, which has the effect of lowering blood lipid, lowering blood pressure and promoting blood circulation to remove blood stasis. At present, the research on Panax notoginseng is mainly focused on its pharmacological action and its compound preparation, but the research on the granule of Panax notoginseng is less. This paper mainly studied the clinical study of compound notoginseng nanoparticles in the treatment of local infection in patients with hydrocephalus after medium craniocerebral injury in neurosurgery. The purpose of this article is to investigate the effects of compound notoginseng nanoparticles on serum TNF-α, IL-2 and IL-6 in rats with craniocerebral injury and to verify the protective effect of compound notoginseng nanoparticles on the body after craniocerebral injury. In this paper, 90 patients admitted to a hospital in this city were divided into a control group, model group and compound notoginseng nanoparticle group. According to the Zealonga method, the neurological function deficit score of experimental rats in each group was evaluated. The levels of TNF-α, IL-2 and IL-6 in the serum of the three groups were observed 1, 3 and 5 days after treatment. RESULTS: Compared with serum TNF-α, IL-2 and IL-6 of the three groups, there were significant differences in the main effects of time and intervention (P < 0.05). CONCLUSIONS: Compound notoginseng nanoparticles can reduce the contents of TNF-α and IL-6 in serum and increase the expression of IL-2 in rats with craniocerebral injury.

Survey evaluating clinical equipoise around platelet transfusion after head injury and traumatic intracranial haemorrhage (ICH) in patients on antiplatelet medications.

INTRODUCTION: Patients aged 60 or over account for over half of the severely injured trauma patients and a traumatic brain injury is the most common injury sustained. Many of these patients are taking antiplatelet medications but there is clinical equipoise about the role of platelet transfusion in patients with traumatic intracranial haemorrhage (ICH) taking prior antiplatelet medications. METHOD: A prepiloted survey was designed to explore a range of clinical issues in managing patients taking antiplatelet medications admitted with a traumatic brain injury. This was sent via email to consultants and specialty registrar members of a variety of relevant UK societies and working groups in the fields of emergency medicine, critical care, neurosurgery and haematology. RESULTS: 193 responses were received, mostly from colleagues in emergency medicine, neurosurgery, anaesthesia and haematology. Respondents indicated that there is a lack of evidence to support the use of platelet transfusion in this patient population but also lack of evidence of harm. Results also demonstrate uncertainties as to whether platelets should be given to all or some patients and doubt regarding the value of viscoelastic testing. DISCUSSION: Our survey demonstrates equipoise in current practice with regards to platelet transfusion in patients with a traumatic ICH who are taking antiplatelet medication. There is support for additional trials to investigate the effect of platelet transfusion in this rising population of older, high-risk patients, in order to provide a better evidence-base for guideline development.

Evaluation of Neuroprotective Effects of Sugammadex Following a Head Trauma in an Experimental Study.

ABSTRACT: To compare the efficacy of mannitol, the first choice of treatment in daily clinical practice for head trauma, and sugammadex, a frequently used neuroanesthesia in recent years. A total of 35 male rats were randomly selected and were divided into 5 groups, each comprising 7 rats. The groups were divided into Group I, sham (n = 7); Group II, control (head trauma, n = 7); Group III, treated with mannitol (head trauma, mannitol 20% 1 g/kg, n = 7); Group IV, treated with sugammadex (head trauma, sugammadex 100 mg/ kg, n = 7); and Group V, treated with mannitol and sugammadex (head trauma, mannitol 20% 1 g/kg and sugammadex 100 mg/kg, n = 7). After the sacrification, histological examination and immu-nohistochemical staining were performed in the brain of all subjects. Mann-Whitney U test was used to evaluate the significance between neuronal density, neuronal nuclei, and activated caspase-3 immunohistochemistry results measured from the prefrontal cortex. Neuronal density showing neuronal viability was observed to significantly increase in Group III compared to Group IV. However, neuronal nuclei immunohistochemistry showing apoptotic neurons also significantly increased. The present study has shown that sugammadex, an agent reversing the effects of neuromuscular blocking agents, has neuroprotective effects and is as effective as mannitol.

Prehospital ketamine administration to pediatric trauma patients with head injuries in combat theaters.

BACKGROUND: Head injuries frequently occur in combat. Tactical Combat Casualty Care (TCCC) guidelines recommend pre-hospital use of ketamine for analgesia. Yet the use of this medication in patients with head injuries remains controversial, particularly among pediatric patients. We compare survival to hospital discharge rates among pediatric head injury subjects who received prehospital ketamine versus those who did not. METHODS: We queried the Department of Defense Trauma Registry (DODTR) for all pediatric (<18 years of age) subjects from January 2007 to January 2016. We performed a sub-analysis of subjects with an abbreviated injury severity score for the head of 3 (serious) or higher and at least one documented Glasgow Coma Score (GCS) ≤13. RESULTS: Of the 3439 pediatric patients within our dataset, 555 subjects met inclusion criteria for head injury - 36 (6.5%) received prehospital ketamine versus 519 (93.5%) who did not. There was no significant difference noted between groups regarding median age (10 versus 8, p = 0.259), percent male gender (72.2% versus 76.3%, p = 0.579), mechanism of injury (p = 0.143), median composite injury scores (22 versus 20, p = 0.082), median ventilator-free days (28 versus 27, p = 0.068), median ICU-free days (27.5 versus 27, p = 0.767), median hospital days (3.5 versus 4, p = 0.876) or survival to discharge (66.7% versus 70.7%, p = 0.607). CONCLUSIONS: Within this data set, we were unable to detect any differences in mortality among pediatric head trauma subjects administered ketamine compared to subjects not receiving this medication in the prehospital setting.

Incidence of intracranial bleeding in anticoagulated patients with minor head injury: a systematic review and meta-analysis of prospective studies.

Guidelines advise performing a computed tomography head scan for all anticoagulated head injured patients, but the risk of intracranial haemorrhage (ICH) after a minor head injury is unclear. We conducted a systematic review and meta-analysis to determine the incidence of ICH in anticoagulated patients presenting with a minor head injury and a Glasgow Coma Score (GCS) of 15. We followed Meta-Analyses and Systematic Reviews of Observational Studies guidelines. We included all prospective studies recruiting consecutive anticoagulated emergency patients presenting with a head injury. Anticoagulation included vitamin-K antagonists (warfarin, fluindione), direct oral anticoagulants (apixaban, rivaroxaban, dabigatran and edoxaban) and low molecular weight heparin. A total of five studies (including 4080 anticoagulated patients with a GCS of 15) were included in the analysis. The majority of patients took vitamin K antagonists (98·3%). There was significant heterogeneity between studies with regards to mechanism of injury and methods. The random effects pooled incidence of ICH was 8·9% (95% confidence interval 5·0-13·8%). In conclusion, around 9% of patients on vitamin K antagonists with a minor head injury develop ICH. There is little data on the risk of traumatic intracranial bleeding in patients who have a GSC 15 post-head injury and are prescribed a direct oral anticoagulant.

Favourable outcome in a child with symptomatic diagnosis of Glutaric aciduria type 1 despite vertical HIV infection and minor head trauma.

The first case of Glutaric aciduria Type 1(GA1) in an African child was reported in 2001. GA1 has a prevalence of 1:5000 in black South Africans. Although early diagnosis is essential for a favourable outcome, newborn screening is not routine in South Africa where an estimated 320,000 children have HIV infection. Neurodevelopmental delay and encephalopathy are complications of both HIV and GA1. In such a setting it is important to recognise that HIV and GA1 can occur simultaneously. We present an HIV-infected South African male child of Xhosa descent with macrocephaly who commenced combination antiretroviral therapy (ART) at 8 weeks of age in a clinical trial which included a neurodevelopmental sub-study. He developed short-lived focal seizures at 16 months after minor head trauma. Neurological examination was normal. Neuroimaging showed temporal lobe atrophy, subtle hyperintense signal change in the globus pallidus, and focal haemosiderosis in the right Sylvian fissure region. As findings were not in keeping with HIV encephalopathy, a urine metabolic screen was undertaken which suggested GA1. Genetic testing confirmed Arg293Trp mutation. He began L-carnitine and a low protein diet as a restricted diet was not practicable. At 21 months he developed pulmonary tuberculosis, requiring 6 months treatment. He did not develop any neurologic motor symptoms. Serial neurodevelopmental and neuropsychological test scores until 9 years were similar to healthy neighbourhood controls, except for mild language delay at 3½ years. Detection of GA1, probably facilitated through participation in a clinical trial, was pivotal for a favourable outcome. The concomitant use of ART and anti-tuberculous therapy in a child with GA1 appears safe.

Intracranial complications after minor head injury (MHI) in patients taking vitamin K antagonists (VKA) or direct oral anticoagulants (DOACs).

INTRODUCTION: The correlation between chronic direct oral anticoagulants (DOACs) intake and the incidence of intracranial complications after minor head injury (MHI) is still not well defined. This study examined the incidence of complications in patients receiving vitamin K antagonists (VKA) or DOACs observed in the emergency department (ED) for MHI. METHODS: Two hundred twenty-five patients affected by MHI and receiving oral anticoagulants were recorded between January and December 2016, distinguishing those treated with VKA (118) from those receiving DOACs (107). All patients underwent a CT scan and were observed for 24h in the ED. Follow-up was performed up to 1month after the head trauma. RESULTS: The rate of intracranial hemorrhage was significantly lower in patients treated with DOACs than in patients treated with VKA. We recorded 2 deaths among the 12 patients who experienced intracranial complications in the VKA group. DISCUSSION: DOACs seem to have a more favorable safety profile than VKA in patients affected by MHI. This observation is important in light of the increasing number of elderly patients who are receiving anticoagulant therapy.

Effects of dexmedetomidine on TNF-α and interleukin-2 in serum of rats with severe craniocerebral injury.

BACKGROUND: Dexmedetomidine is a highly selective adrenergic receptor agonist, which has a dose-dependent sedative hypnotic effect. Furthermore, it also has pharmacological properties, and the ability to inhibit sympathetic activity and improve cardiovascular stability during an operation. However, its protective effect on patients with severe craniocerebral injury in the perioperative period remains unclear. METHOD: Eighty adult male SD rats were used and divided into two groups (n = 40, each group): dexmedetomidine injury group (experimental group), and sodium chloride injury group (control group). Models of severe craniocerebral injury were established in these two groups using the modified Feeney's free-fall method. As soon as the establishment of models was succeed, rat in the experimental group received 1 µg of dexmedetomidine (0.1 ml), while each rat in the control group was given 0.1 ml of 0.9% sodium chloride. Blood was sampled from an incision at the femoral vein to detect TNF-α and IL-2 levels at 1, 12, 24,36,48 and 72 h after establishing the model in the two groups. RESULTS: After severe craniocerebral injury, TNF-α levels of rats were lower in every stage and at different degrees in the experimental group than in the control group (P < 0.05), while IL-2 levels were lower in the experimental group to different extents (P < 0.05). CONCLUSION: Dexmedetomidine protects the brain of rats with severe craniocerebral injury by reducing the release of inflammatory mediators.

Risk Factors for Cerebral Venous Thrombosis.

Cerebral venous thrombosis (CVT) is a rare thrombotic disorder involving the cerebral veins and dural sinuses. In contrast to more common sites of venous thromboembolism (VTE), such as the legs and lungs, CVT mainly affects young adults and children, and women are affected three times more often than men. Although presenting symptoms are variable, headache is usually the first symptom, often in combination with focal neurologic deficits and epileptic seizures. The primary therapy for CVT consists of heparin followed by oral anticoagulation for at least 3 to 6 months. The mortality in the acute phase is 5 to 10% and a substantial proportion of survivors suffer from long-term disabilities. A large number of risk factors have been linked to CVT, although the scientific evidence for an association varies considerably between risk factors. Some risk factors, such as hereditary thrombophilia, correspond with risk factors for more common sites of VTE, whereas others, such as head trauma, are specific to CVT. In most patients, at least one risk factor can be identified. In this review, we provide an overview of the risk factors for CVT.

S100B and the influence of seasonal variation.

Background A blood test for S100B can be used to rule out intracranial complications after minor head injury and thereby reduce the need for computed tomography (CT) examinations. The aim of this study was to investigate the clinical importance of a possible influence of seasonal variation on S100B. Methods The individual seasonal variation of S100B in 69 healthy volunteers living at latitudes with extremely variable seasonal exposure to sunlight was investigated. Results The mean serum concentration of S100B was 13% higher in August than in February, but however, not statistically significant (p = 0.068). A good agreement between summer and winter S100B values was confirmed by Bland-Altman analysis and a significant correlation (r = 0.317, p = 0.008) was shown between summer and winter S100B values. Conclusion This study did not show any clinical importance of seasonal variation of S100B that may influence the decision of CT scanning patients with head injuries.

S100B serum protein cannot predict secondary intracranial haemorrhage after mild head injury in patients with low-dose acetylsalicylic acid prophylaxis.

INTRODUCTION: The goal of this study was to investigate if S100B serum protein could predict secondary intracranial haemorrhagic events (SIHEs) after mild head injury (mHI) in patients taking low-dose acetylsalicylic acid (LDA), making routinely repeated head computed tomography (RRHCT) scans unnecessary. METHODS: Three hundred and eight-two patients with mHI, older than 60 years and taking LDA prophylaxis were enrolled. Primary head CT and RRHCT scans within 3 and 48 hours to trauma were performed. Additionally, S100B serum protein levels were evaluated at admission and predictive power for SIHEs was analysed. RESULTS: Fifty-nine per cent were female and the mean age of all included patients was 81.8 ± 8.9 years. In four patients SIHEs were diagnosed. Sensitivity and the negative predictive value of S100B serum protein (cut-off value 0.10 µg l(-1)) were 75.0% and 98.6%, respectively. Specificity was 19.0% and the positive predictive value 1.0% (306 false positive values). In patients without bleeding, the median S100B value was 0.18 (IQR = 0.12-0.34) and in the ones with SIHEs, the median was 0.11 (IQR = 0.10-1.16) (p > 0.05). The discriminatory power of S100B in the ROC analysis was 0.399 (95% CI = 0.079-0.720; p > 0.05). CONCLUSION: S100B cannot be considered as an effective diagnostic tool in the prediction or exclusion of SIHE in older patients with mHIs taking LDA prophylaxis.

Why is it so difficult to recruit patients to research in emergency care? Lessons from the AHEAD study.

INTRODUCTION: In February 2014, all 23 National Institute for Health Research medical research specialities were failing to meet recruitment targets, with 'Injuries and Emergencies' research performing particularly poorly. In this paper, the multicentre AHEAD study was used to explore issues surrounding recruitment in UK emergency departments. METHOD: The AHEAD study investigated management and outcomes in over 3000 anticoagulated patients who suffered a head injury. Data from the study were used to compare patient recruitment at 33 Type-1 emergency departments. A questionnaire was sent to a research nurse at each of these sites and 30 replied (91% response rate). The survey investigated the difficulties encountered during patient recruitment and whether these were related to recruitment methods. More detailed interviews were conducted with three research nurses, to gain further insight into the barriers and facilitators involved. RESULTS: Overall recruitment varied widely between sites with an eightfold variation in recruitment rates. Population demographics and other uncontrollable factors will partly contribute to this variation. However, research nurses reported many problems, including site resources, lack of staff engagement and flaws in recruitment strategies, which could be improved. CONCLUSIONS: Many of the barriers to recruiting patients for research studies encountered by research nurses have previously been reported in the literature, but there remain consistent problems. Until solutions are found, researchers will continue to miss recruitment targets and this will have implications for the efficiency and quality of emergency medicine research in the UK.

INTRA-ARTERIAL INFUSIONS AND DOPLEROGRAPIC CONTROL FOR COMPLEX TREATMENT OF UPPER AND MIDDLE FACIAL ZONES, CONCOMITANT WITH TRAUMATIC CRANIOCEREBRAL INJURIES.

Maxillofacial traumatic injuries concomitant with craniocerebral trauma are still considered as an actual problem in emergency medicine. For this category of patients one of the dangerous and severe complications is development of inflammatory process in the injured areas. Fracture lines of upper and middle facial zones pass through the accessory sinuses of the nose, maxillary/upper dental arch area and are considered to be open and infected fractures. Combination of these fractures with craniocerebral injuries and especially, with open traumas creates predisposition for development of inflammatory processes in CNS that can result in heavy outcome. 29 patients (among them 5-females and 24 -males) with severe and open craniofacial fractures were observed by the authors. For prevention of inflammatory complications in complex treatment of the patients, intra-arterial infusions of therapeutic agents (wide spectrum of antibiotics, Heparin) were used for stimulation of reparative regeneration in fractured fragments of facial bones. After the main surgical interventions (neurosurgery, surgery of facial bones) sanitation of infected centers (accessory sinuses of the nose, oral cavity) and catheterization of external carotid arteries through the temporal arteries were performed. According to the severity of the trauma and its preferential localization, catheterization of carotid arteries was conducted unilaterally (12 cases) or bilaterally (17 cases). Insertion depth through femoral artery was 6-8 cm. Catheter was stayed in the artery for 7-8 days. Intra-arterial infusions were carried out in the morning and evening. Therapeutic agents for arterial infusion included: antibiotic (Rocephin and its analogues), Heparin. To determine the effectiveness of vascular therapy dopplerography of external carotid artery, its branches and supratrochlear artery was performed. Dopplerography of supratrochlear artery, which is the branch of internal carotid artery, was conducted to detect the impact of therapeutic agents, administered in external carotid artery, on the internal carotid artery. During the treatment of complicated concomitant craniofacial injuries in a sequential order, development of inflammatory processes was not observed even in the patients with basic inflammatory processes in accessory sinuses of the nose. After infusion of therapeutic agents to external carotid artery, dopplerographically, sharp increase in blood flow in main artery and its branches, indicates to the stimulation of microcirculation that serves as a guarantee for osteogenic type healing of fractured fragments.

Prevention of Sports Injuries by Marine Omega-3 Fatty Acids.

Sport injuries are common and costly for the professional athlete, the "weekend warrior," and the community. Acute injuries are treated according to current guidelines with the aim of bringing the athlete back into the arena. These guidelines have not taken into account new scientific results of the inflammatory process following a trauma. The 4 hallmarks of inflammation, namely, pain, swelling, redness, and heat, are results of an adequate inflammatory response with the aim of bringing the affected tissue back to restitution (Latin: restitutio ad integrum). Cooling of the affected limb and anti-inflammatory drugs are widely used but may deter healing. The healing process is governed by fatty acids of the omega-3 and omega-6 series. In order to facilitate healing, these fatty acids have to be present in significant amounts in the affected tissues before the trauma occurs. This is particularly relevant for marine omega-3 fatty acids, which are often running low due to insignificant intake of seafood, common in individuals practicing sports. High-energy sports often lead to head and brain trauma. Continuous head traumata may even result in later mental defects. Saturation of brain cells with omega-3 fatty acids, in particular docosahexaenoic acid (DHA), may facilitate healing after brain trauma, thereby counteracting negative long-term results. The present understanding of a normal inflammatory process leading to restitution will be discussed along with data from recent scientific trials.

Deficiency of complement receptors CR2/CR1 in Cr2⁻/⁻ mice reduces the extent of secondary brain damage after closed head injury.

Complement activation at the C3 convertase level has been associated with acute neuroinflammation and secondary brain injury after severe head trauma. The present study was designed to test the hypothesis that Cr2-/- mice, which lack the receptors CR2/CD21 and CR1/CD35 for complement C3-derived activation fragments, are protected from adverse sequelae of experimental closed head injury. Adult wild-type mice and Cr2-/- mice on a C57BL/6 genetic background were subjected to focal closed head injury using a standardized weight-drop device. Head-injured Cr2-/- mice showed significantly improved neurological outcomes for up to 72 hours after trauma and a significantly decreased post-injury mortality when compared to wild-type mice. In addition, the Cr2-/- genotype was associated with a decreased extent of neuronal cell death at seven days post-injury. Western blot analysis revealed that complement C3 levels were reduced in the injured brain hemispheres of Cr2-/- mice, whereas plasma C3 levels remained unchanged, compared to wild-type mice. Finally, head-injured Cr2-/- had an attenuated extent of post-injury C3 tissue deposition, decreased astrocytosis and microglial activation, and attenuated immunoglobulin M deposition in injured brains compared to wild-type mice. Targeting of these receptors for complement C3 fragments (CR2/CR1) may represent a promising future approach for therapeutic immunomodulation after traumatic brain injury.