Secondary Neurological Injury Research Articles

Single Institution Experience with Lumbar Drainage and Subarachnoid Hemorrhage

In our paper, we evaluate the effect of lumbar drainage on delayed cerebral ischemia and requirements for permanent cerebrospinal fluid diversion in patients with aneurysmal subarachnoid hemorrhage. We performed a retrospective cohort study from 2014-2023 at the University of Arkansas for Medical Sciences (UAMS) examining factors associated with patients (n=150) who had aneurysmal subarachnoid hemorrhage and a lumbar drain placed. Main outcomes examined were incidence of delayed cerebral ischemia, need for permanent cerebrospinal fluid diversion, and neurologic outcomes at discharge that were compared to currently published standards. We failed to appreciate a reduced occurrence of delayed cerebral ischemia (37.3% with the current literature supporting rates of 20-30%); however, we did find a low rate of requiring permanent cerebrospinal fluid diversion (12% compared to 10-20% in the current literature) with overall good neurologic outcomes at discharge (~69% of patients had a Glasgow Outcome Scale (GOS) of 4-5 at discharge). Patients with GOS≥4 at discharge were noted to be more likely to have more days or lumbar drainage and less likely to be older than 65, have had an external ventricular drain placed, and have experienced delayed cerebral ischemia. Lumbar drainage is a potentially useful adjunct in the management of secondary neurologic injury in subarachnoid hemorrhage.

Pharmacologic Therapy for Spinal Cord Injury.

Neuroprotective strategies aimed at preventing secondary neurologic injury following acute spinal cord injury remain an important area of clinical, translational, and basic science research. Despite recent advancement in the understanding of basic mechanisms of primary and secondary neurologic injury, few pharmacologic agents have shown consistent promise in improving neurologic outcomes following SCI in large randomized clinical trials. The authors review the existing literature and clinical guidelines for pharmacologic therapy investigated for managing acute SCI, including corticosteroids, GM-1 ganglioside (Sygen), Riluzole, opioid antagonists, Cethrin, minocycline, and vasopressors for mean arterial pressure augmentation. Therapies for managing secondary effects of SCI, such as bradycardia, are discussed. Current clinical trials for pharmacotherapy and cellular transplantation following acute SCI are also reviewed. Despite the paucity of current evidence for clinically beneficial post-SCI pharmacotherapy, future research efforts will hopefully elucidate promising therapeutic agents to improve neurologic function.

GSTO2 ameliorates human neuroblastoma cell apoptosis, inflammation, ferroptosis, and oxidative stress by upregulating GPX4 expression in intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a severe hemorrhagic stroke and induces severe secondary neurological injury. However, its pathogenesis remains to be explored. The present work investigates the role of glutathione S-transferase omega 2 (GSTO2) in ICH and the underlying mechanism. Human neuroblastoma cells (SK-N-SH) were stimulated using hemin to mimic ICH-like injury. Protein expression levels of GSTO2 and glutathione peroxidase 4 (GPX4) were detected by western blot analysis assay. Cell viability was assessed by cell counting kit-8 assay. Cell proliferation was investigated by 5-ethynyl-2'-deoxyuridine assay. Cell apoptosis was analyzed by flow cytometry. Interleukin-6 and tumor necrosis factor-α levels were quantified by enzyme-linked immunosorbent assays. Fe2+ colorimetric assay kit was used to detect Fe2+ level. A cellular reactive oxygen species (ROS) assay kit was used to detect ROS levels. Malondialdehyde (MDA) level was assessed using the MDA content assay kit. GSH level was quantified using the GSH assay kit. Co-immunoprecipitation assay was performed to identify the association between GSTO2 and GPX4. Hemin stimulation suppressed SK-N-SH cell proliferation and promoted cell apoptosis, cell inflammation, ferroptosis, and oxidative stress. GSTO2 expression was downregulated in hemin-treated SK-N-SH cells in comparison with the control group. In addition, ectopic GSTO2 expression counteracted hemin-induced inhibitory effect on cell proliferation and promoting effects on cell apoptosis, inflammation, ferroptosis, and oxidative stress. Moreover, GSTO2 was associated with GPX4 in SK-N-SH cells. GPX4 silencing attenuated GSTO2 overexpression-induced effects on hemin-stimulated SK-N-SH cell injury. GSTO2 ameliorated SK-N-SH cell apoptosis, inflammation, ferroptosis, and oxidative stress by upregulating GPX4 expression in ICH, providing a therapeutic strategy for ICH.

C.5 Altered inflammatory profiles in critically ill children with neurologic involvement

Background: More than 1 in 4 children admitted to the pediatric ICU (PICU) have suspected neuroinflammation for a variety of reasons. While often beneficial, uncontrolled inflammation can lead to secondary neurologic injuries and interfere with repair mechanisms. Methods: A prospective cohort study was initiated at Alberta Children’s Hospital to evaluate neuroinflammation in children admitted to the PICU. Forty-eight cytokines, chemokines and growth factors collected at multiple pre-determined timepoints were analyzed along with data on clinical trajectory. Preliminary exploratory analyses of patients enrolled January 2022-July 2023 were completed. Results: Fifty-three patients were included in the initial analysis. Encephalopathy (18.9%), hypoxia (17%) and TBI (15.1%) were the most common reasons for enrollment. All groups had temporal alterations in serum cytokines, with primary inflammatory brain diseases having the highest levels of innate inflammation (cytokine storm) on admission and day one compared to other subgroups. There was a trend towards normalization of cytokine levels over time. Conclusions: Temporal profiling of cytokine levels can inform on neuroinflammatory pathways contributing to the clinical course in critically ill children. Further analysis is ongoing with the entire cohort to evaluate longitudinal and between-group differences. Improved understanding of altered neuroinflammatory pathways in this population may assist with rationalizing targeted immunotherapies to improve outcomes.

Dihydrotestosterone reduces neuroinflammation in spinal cord injury through NF-κB and MAPK pathway.

Neuroinflammation induced by microglia following spinal cord injury (SCI) leads to secondary neurologic injury. Androgens including testosterone and dihydrotestosterone (DHT) show as endogenous neuroprotective factors against multiple neurologic diseases, while their therapeutic role in SCI-induced neuroinflammation and underlying mechanism remains elusive. In the study, we aimed to investigate the role of DHT against microglia-induced neuroinflammation in SCI and evaluate its protective treatment. BV2 cells were activated by neuroinflammation via LPS in vitro. Adult male C57BL/6 mice were used to establish the SCI model. BV2 cells and SCI mice were administrated DHT. Microglia activation, pro-inflammatory factors, p38 and p65 phosphorylation, glial scar, fibrotic scar, histology, and locomotor function recovery were measured, respectively. We demonstrated that DHT administration attenuates neuroinflammation in microglia through inhibition of p38 and p65 pathways. Moreover, DHT reduces microglia and astrocyte accumulation, cord fibrosis and histologic damage. Besides, DHT ameliorates locomotor functional recovery after SCI. DHT is verified to play a neuroprotective role in SCI, which fights against neuroinflammation by inhibition of p38 and p65 pathways. Therefore, Mel is defined as a promising factor in protecting neural tissue after SCI.

Differential Diagnosis and Management of Disturbance of Consciousness:Approach to Comatose Patients

Disorders of consciousness are among the most common symptoms in neurosurgery. A coma is an acute dysfunction of the nervous system that governs arousal and awareness and represents a medical emergency. Prompt evaluation and treatment of comas are fundamental in clinical practice. The first step is stabilizing the airway, breathing, and circulation while protecting the cervical spine to prevent secondary neurological injury. Subsequently, a focused neurological examination is performed. The level of consciousness, brainstem reflexes, respiratory patterns, motor responses, and muscle tone should be evaluated. Any asymmetry should be carefully considered. Acute disturbances of consciousness primarily impair arousal. The Japan and Glasgow Coma Scales are the most commonly used. The Emergency Coma Scale was designed by incorporating the advantages of each. The Full Outline of UnResponsiveness score incorporates brainstem reflexes and breathing patterns. Clinicians must have an organized approach to detect remediable causes, prevent neurological injury, and determine a hierarchical course of diagnostic testing, treatments, and neuromonitoring.

Interleukin-6 in Traumatic Brain Injury: A Janus-Faced Player in Damage and Repair.

Traumatic brain injury (TBI) is a common and often devastating illness, with wide-ranging public health implications. In addition to the primary injury, victims of TBI are at risk for secondary neurological injury by numerous mechanisms. Current treatments are limited and do not target the profound immune response associated with injury. This immune response reflects a convergence of peripheral and central nervous system-resident immune cells whose interaction is mediated in part by a disruption in the blood-brain barrier (BBB). The diverse family of cytokines helps to govern this communication and among these, Interleukin (IL)-6 is a notable player in the immune response to acute neurological injury. It is also a well-established pharmacological target in a variety of other disease contexts. In TBI, elevated IL-6 levels are associated with worse outcomes, but the role of IL-6 in response to injury is double-edged. IL-6 promotes neurogenesis and wound healing in animal models of TBI, but it may also contribute to disruptions in the BBB and the progression of cerebral edema. Here, we review IL-6 biology in the context of TBI, with an eye to clarifying its controversial role and understanding its potential as a target for modulating the immune response in this disease.

Approaches to neuroprotection in pediatric neurocritical care.

Acute neurologic injuries represent a common cause of morbidity and mortality in children presenting to the pediatric intensive care unit. After primary neurologic insults, there may be cerebral brain tissue that remains at risk of secondary insults, which can lead to worsening neurologic injury and unfavorable outcomes. A fundamental goal of pediatric neurocritical care is to mitigate the impact of secondary neurologic injury and improve neurologic outcomes for critically ill children. This review describes the physiologic framework by which strategies in pediatric neurocritical care are designed to reduce the impact of secondary brain injury and improve functional outcomes. Here, we present current and emerging strategies for optimizing neuroprotective strategies in critically ill children.

Cortical Spreading Depolarization and Delayed Cerebral Ischemia; Rethinking Secondary Neurological Injury in Subarachnoid Hemorrhage.

Poor outcomes in Subarachnoid Hemorrhage (SAH) are in part due to a unique form of secondary neurological injury known as Delayed Cerebral Ischemia (DCI). DCI is characterized by new neurological insults that continue to occur beyond 72 h after the onset of the hemorrhage. Historically, it was thought to be a consequence of hypoperfusion in the setting of vasospasm. However, DCI was found to occur even in the absence of radiographic evidence of vasospasm. More recent evidence indicates that catastrophic ionic disruptions known as Cortical Spreading Depolarizations (CSD) may be the culprits of DCI. CSDs occur in otherwise healthy brain tissue even without demonstrable vasospasm. Furthermore, CSDs often trigger a complex interplay of neuroinflammation, microthrombi formation, and vasoconstriction. CSDs may therefore represent measurable and modifiable prognostic factors in the prevention and treatment of DCI. Although Ketamine and Nimodipine have shown promise in the treatment and prevention of CSDs in SAH, further research is needed to determine the therapeutic potential of these as well as other agents.

Ceramide in cerebrovascular diseases.

Ceramide, a bioactive sphingolipid, serves as an important second messenger in cell signal transduction. Under stressful conditions, it can be generated from de novo synthesis, sphingomyelin hydrolysis, and/or the salvage pathway. The brain is rich in lipids, and abnormal lipid levels are associated with a variety of brain disorders. Cerebrovascular diseases, which are mainly caused by abnormal cerebral blood flow and secondary neurological injury, are the leading causes of death and disability worldwide. There is a growing body of evidence for a close connection between elevated ceramide levels and cerebrovascular diseases, especially stroke and cerebral small vessel disease (CSVD). The increased ceramide has broad effects on different types of brain cells, including endothelial cells, microglia, and neurons. Therefore, strategies that reduce ceramide synthesis, such as modifying sphingomyelinase activity or the rate-limiting enzyme of the de novo synthesis pathway, serine palmitoyltransferase, may represent novel and promising therapeutic approaches to prevent or treat cerebrovascular injury-related diseases.

ADAM17 aggravates the inflammatory response by modulating microglia polarization through the TGF-β1/Smad pathway following experimental traumatic brain injury.

Microglia-mediated neuroinflammatory responses play important roles in secondary neurological injury after traumatic brain injury (TBI). The TGF-β pathway participates in the regulation of M1/M2 phenotype transformation of microglia. TGF-β can activate the Smad pathway by binding to TGF-βRs, which is regulated by the cleavage function of A disintegrin and metalloproteinase 17 (ADAM17). However, the role of ADAM17 and the associated signaling pathways in the pathological process after TBI remain unclear. Herein, we assessed the transformation of microglia M1/M2 phenotype polarization and the neuroinflammatory response after the inhibition of ADAM17. The formation of TGF-βRs and TGF-β1/TGF-βRII complexes on microglia were detected to evaluate the effect of ADAM17 inhibition on the TGF-β1/Smad pathway. ADAM17 was highly expressed after TBI and mainly located in the microglia. the inhibition of ADAM17 improved neurological function after TBI. The neuroprotective effect of ADAM17 inhibition was related to a shift from the M1 microglial phenotype to the M2 microglial phenotype, thus reducing TBI-induced neuroinflammation. ADAM17 inhibition increased expression of TGF-βRs on the microglia membrane, promoted formation of TGF-β1/TGF-βRII complexes, and induced intranuclear translocation of Smads, which activated the TGF-β/Smad pathway. In conclusion, our study suggested that ADAM17 inhibition regulated microglia M1/M2 phenotype polarization through the TGF-β1/Smad pathway and influenced the neuroinflammatory response after TBI.

Post-traumatic Seizures in Children with Abusive Head Trauma (S2.007)

<h3>Objective:</h3> Our objectives were to study the incidence and risk factors for PTS, utilization of continuous EEG (cEEG), management with anti-epileptic drugs (AEDs) and clinical outcomes in victims of AHT. <h3>Background:</h3> Abusive head trauma (AHT) causes death and disability in children. Post-traumatic seizures (PTS) are common in AHT and cause secondary neurological injury. The study of the characteristics and true burden of PTS is important to develop effective management strategies. <h3>Design/Methods:</h3> We assembled an eleven-year cohort of children aged 0–3 years, who suffered AHT and were subsequently admitted to an academic children’s hospital. Data pertinent to demographics, clinical features, management and follow up were collected by retrospective chart review and analyzed. <h3>Results:</h3> Sixty out of ninety-two AHT victims developed PTS during hospitalization. Mean age was 6 ±5.8 months and predominantly consisted of males (65%). Factors associated with higher likelihood of seizures were subdural hematoma (OR 5.32 [95% CI 1.27–22.2]) and comorbidities like prematurity (OR 5.45 [95% CI 1.16–25.48]). Over 90% of PTS, occurred within a week of hospitalization. Of those, only three cases had purely electrographic seizures. Mean time to cEEG initiation was 14.7 hours. Nearly 50% of seizures continued sub-clinically, despite clinical control. Although levetiracetam was most commonly used, monotherapy with the same was ineffective in &gt;50%. In comparison to AHT patients without seizures, PTS patients had longer ICU and hospital stays, by 4.1 and 7.8 days respectively. Although, majority (80%) were discharged on AEDs, 40% were weaned off at follow-up. Among PTS patients, mortality rate was &lt;5% with the most common long-term sequelae being developmental delay and epilepsy. <h3>Conclusions:</h3> To date, this is the largest cohort study to examine PTS in young AHT victims. While most PTS were clinical and occurred early, cEEG monitoring was essential in detection and treatment of subclinical seizures. Overall, PTS had a good survival rate and outcomes. <b>Disclosure:</b> Dr. Ahmed Khan has nothing to disclose. Dr. Goretzke has nothing to disclose. Dr. Calamur has nothing to disclose.

Characterizing the Use of Intrathecal Nicardipine for Post Traumatic Cerebral Vasospasm (P13-7.005)

<h3>Objective:</h3> Characterizing the use of intrathecal nicardipine for post traumatic cerebral vasospasm and treatment-related complications. <h3>Background:</h3> Post traumatic cerebral vasospasm (PTV) is a significant cause of secondary neurologic injury after traumatic brain injury (TBI) and is associated with worse outcomes. There is limited data to guide treatment of PTV. Intrathecal nicardipine (ITn) was shown to improve outcomes and reduce delayed cerebral ischemia in non-traumatic subarachnoid hemorrhage (SAH) patients, but traumatic mechanisms were not well studied. In this retrospective study, we characterize the use of ITn for PTV at a high-volume trauma center. <h3>Design/Methods:</h3> We reviewed all TBI admissions at a high-volume trauma center over a 10-year period. Patients ≥18 years of age requiring external ventricular drain (EVD) placement were included. We collected data regarding injury severity, length of stay, rationale, and timing for initiation of ITn, dosing, frequency and treatment-related complications. <h3>Results:</h3> Seven patients with severe TBI received ITn for radiographic vasospasm (VSP) on surveillance imaging. The average duration of treatment was 6 days. ITn was stopped given radiographic improvement (4), pre-defined decision for 48 hours of treatment (1), after DSA revealed no VSP (1) or identification of ventriculitis (1). Three patients had delayed cerebral ischemia on imaging; however, these were noted before the initiation of ITn. Two patients developed ventriculitis and one patient had brief, elevated intracranial pressure spikes with ITn. <h3>Conclusions:</h3> ITn is rarely used for PTV in this high-volume center. When ordered, it is done for radiographic VSP with variations in practice patterns for dosing, duration and weaning. Given the possible benefit of ITn in non-traumatic SAH patients and otherwise limited treatment options for PTV, understanding ITn use and outcomes in PTV is warranted. <b>Disclosure:</b> Dr. Sigman has nothing to disclose. Dr. Chester has nothing to disclose. Dr. Sciarretta has nothing to disclose. The institution of Dr. Ratcliff has received research support from Nico Corporation. The institution of Dr. Ratcliff has received research support from Sense . Ofer Sadan has received intellectual property interests from a discovery or technology relating to health care.

Effect of clevidipine on intracranial pressure in pediatric neurosurgical patients: a single-center retrospective review.

Hemodynamic management in pediatric neurosurgical patients is essential for maintaining cerebral perfusion pressure (CPP), avoiding hemorrhage, and preventing secondary neurological injury. Antihypertensive infusions approved for pediatrics are not widely studied in the pediatric neurosurgical population and may have adverse effects on intracranial pressure (ICP), contributing to reduced CPP. Clevidipine is an ultra-rapid-acting intravenous antihypertensive agent used for hemodynamic control in adult surgical patients. In pediatric patients, clevidipine is safe and effective in controlling blood pressure in the perioperative period, although studies evaluating its effect on ICP in neurosurgical patients are lacking. The objective of this research was to evaluate the effect of clevidipine on ICP in pediatric neurosurgical patients. This single-center retrospective study involved patients admitted to the pediatric ICU between January 1, 2017, and December 31, 2020. Patients eligible for inclusion had ICP monitoring devices and received clevidipine infusion for a minimum of 6 hours postoperatively, with at least one ICP measurement pre- and postinfusion. Excluded patients had an elevated preinfusion ICP > 20 mm Hg. The primary outcome was the average change in ICP from preinfusion baseline to hours 6 to < 12, 12 to < 24, and 24 to < 48 of clevidipine infusion. Secondary outcomes included frequency of ICP measurements > 20 mm Hg, CPP measurements < 50 mm Hg, treatment failure defined by a need for concurrent antihypertensive infusion, and frequency of elevated serum triglycerides > 200 mg/dL. Descriptive data were expressed as frequency with percentage or median with interquartile range as appropriate. Analysis of continuous outcome variable data involved Mann-Whitney U-tests with an alpha significance of 0.05. Data from 47 patients were included in the analysis. The average change in ICP from preinfusion baseline to 48 hours was < 1 mm Hg. Of 3025 total postinfusion ICP measurements in 47 patients, 67 measurements (2.2%) in 13 patients (28%) were > 20 mm Hg. CPP measurements < 50 mm Hg occurred in 16 of 45 patients (36%). Three patients (6.4%) required use of a secondary antihypertensive medication infusion, and 5 of 14 patients (36%) had serum triglycerides > 200 mg/dL. Use of clevidipine had minimal effect on ICP. The results of this study suggest that clevidipine is effective at safely maintaining ICP and CPP measurements without detrimental adverse effects in pediatric neurosurgical patients.

The Utilization of Critical Care Resources in Pediatric Neurocritical Care Patients.

To define the prevalence of neurologic diagnoses and evaluate the utilization of critical care and neurocritical care (NCC) resources among children admitted to the PICU. Retrospective cohort analysis. Data submitted to the Virtual Pediatric Systems (VPS) database. All children entered in VPS during 2016 (January 1, 2016, to December 31, 2016). None. There were 128,688 patients entered into VPS and were comprised of 24.3% NCC admissions and 75.7% general PICU admissions. The NCC cohort was older, represented more scheduled admissions, and was more frequently admitted from the operating room. The NCC cohort also experienced a greater decline in prehospitalization to posthospitalization functional status and required more frequent use of endotracheal intubation, arterial lines, and foley catheters but had an overall shorter duration of PICU and hospital length of stay with a higher mortality rate. One thousand seven hundred fifteen patients at 12 participating institutions were entered into a novel, pilot NCC module evaluating sources of secondary neurologic injury. Four hundred forty-eight patients were manually excluded by the data entrant, leaving 1,267 patients in the module. Of the patients in the module, 75.8% of patients had a NCC diagnosis as their primary diagnosis; they experienced a high prevalence of pathophysiologic events associated with secondary neurologic insult (ranging from hyperglycemia at 10.5% to hyperthermia at 36.8%). In children admitted to a VPS-contributing PICU, a diagnosis of acute neurologic disease was associated with greater use of resources. We have identified the most common etiologies of acute neurologic disease in the 2016 VPS cohort, and such admissions were associated with significant decrease in functional status, as well as an increase in mortality.

ED BP Management for Subarachnoid Hemorrhage

To review most recent literature on management of blood pressure in acute aneurysmal subarachnoid hemorrhage (SAH) and provide practice recommendations for the emergency clinician. There is increased risk of aneurysmal rebleeding with systolic blood pressure (SBP) greater than 160mmHg in the acute setting. Avoiding large degrees of blood pressure variability improves clinical outcomes in aneurysmal SAH. Acute lowering of SBP to a range of 140-160mmHg decreases risk of rebleeding while also maintaining cerebral perfusion pressure (CPP) after aneurysmal rupture. Treatment with a short acting antihypertensive agent allows for rapid titration of blood pressure (BP) and reduces BP variability. Elevations in intracranial pressure occur commonly after SAH due to increased intracranial blood volume, cerebral edema, or development of hydrocephalus. Clinicians should be familiar with changes in cerebral autoregulation and effects on CPP when treating elevated BP, in order to mitigate the risk of secondary neurological injury.

Curcumin Restrains Oxidative Stress of After Intracerebral Hemorrhage in Rat by Activating the Nrf2/HO-1 Pathway.

Intracerebral hemorrhage (ICH), a severe hemorrhagic stroke, induces cerebral oxidative stress and severe secondary neurological injury. Curcumin was demonstrated to inhibit oxidative stress in the brain after ICH. However, the pharmacological mechanism needs further research. We used an intrastriatal injection of autologous blood to make the rat ICH model, and then the rat was treated with curcumin (100 mg/kg/day). Modified Neurological Severity Score (mNSS) and corner test results showed that curcumin could significantly promote the neurological recovery of ICH rats. Meanwhile, curcumin could substantially reduce ROS and MDA in the tissues around intracranial hematoma and prevent GSH depletion. To explore the pharmacological molecular mechanism of curcumin, we used HAPI cells and primary rat cortical microglia for in vitro experiments. In vitro, heme-treated cells were used as the cell model of ICH to explore the molecular mechanism of inhibiting oxidative stress by curcumin treatment. The results showed that curcumin significantly inhibited heme-induced oxidative stress, decreased intracellular ROS and MDA, and promoted Nrf2 and its downstream antioxidant gene (HO-1, NQO1, and Gpx4) expression. These results suggest that curcumin inhibits oxidative stress by activating the Nrf2/HO-1 pathway. Here, our results indicate that curcumin can promote the inhibition of oxidative stress in microglia by activating the Nrf2/HO-1 pathway and promoting neurological recovery after ICH, providing a new therapeutic target for clinical treatment of ICH.

Approach and considerations for surgery in subaxial cervical spine injury: A narrative review

Subaxial cervical spine injuries are common and encompass a spectrum of injuries ranging from a minor ligamentous sprain to fracture dislocation with spinal cord injury. These injuries are often missed in the initial evaluation, and a high index of suspicion is needed to evaluate and diagnose these injuries, which otherwise could lead to spinal cord injury. Computed tomography scans are the gold standard in the evaluation of fractures as plain radiographs have limited sensitivity. Magnetic resonance imaging (MRI) is necessary to identify injury to the disco-ligamentous complex and to assess cord injury. The principles of the treatment of cervical spine injuries include early immobilization to prevent secondary neurological injury, achieving alignment by reduction and stabilization of the unstable injured segment and decompression of the cord in the presence of cord injury. Owing to a broad spectrum of injuries, there is no unified approach, and the management plan depends on the morphology of injury, the extent of structures damaged, and the presence of neurological impairment. Various classifications grade and help assess the severity of the injury. Minor injuries are conservatively managed with cervical orthoses, and unstable injuries require stabilization either anterior, posterior, or combined approaches, depending on the injury morphology. Controversy exists over the safety of closed reduction in facetal subluxations, need for pre-reduction MRI, and the ideal approach for each injury. This review presents the current evidence and guidelines on the management of subaxial cervical spine injuries.

Interfer(on)-ing with vascular repair after acute brain injury.

Type I interferon response to systemic infections after head trauma or stroke impairs angiogenesis in injured tissues and may contribute to secondary neurological injury.

Disrupting RhoA activity by blocking Arhgef3 expression mitigates microglia-induced neuroinflammation post spinal cord contusion

Excess inflammatory microglia activation deteriorates the pathological degree of spinal cord injury (SCI). We here employed microglia samples in vitro and murine model in vivo to trace the role of inhibition of Arhgef3 in inflammatory response post SCI. From the specimen analysis of lipopolysaccharide (LPS)-induced inflammatory microglia, we found that Arhgef3 expression was positively relative to microglia activation. In vitro, LPS caused the microglia inflammatory activation and induced upregulation of the Arhgef3 expression. Interestingly, presence of Arhgef3 could activate RhoA through promoting Rho GTPases, but silencing of Arhgef3 decreased RhoA activation and inhibited the microglia inflammation. Moreover, disruption of Arhgef3 inhibited the GTP-RhoA, resulted in a suppression of proinflammatory cytokines, and alleviated the LPS-elicited inflammatory genes expression. Moreover, artificially decreasing Arhgef3 expression remarkedly reduced ROS generation after LPS treatment. In vivo of a mouse mechanical contusion-induced SCI model, inhibition of Arhgef3 reduced the ratio of GTP-RhoA/Total-RhoA, and prevented SCI via mitigating the microglial inflammatory phenotype and decreased secondary neurological injury. Besides, inhibition of Arhgef3 prevented alleviated the degree of demyelination but did not affect neuronal regeneration. Meaningfully, absence of Arhgef3 improved mouse locomotor recovery post SCI. Taken together, Arhgef3 involves the microglial activation and inflammatory response following neural injury, and targeted disrupting of which may indicate a promising therapeutic direction in preventing SCI.