Spinal Cord Edema Research Articles

Dexmedetomidine postconditioning alleviates spinal cord ischemia-reperfusion injury in rats via inhibiting neutrophil infiltration, microglia activation, reactive gliosis and CXCL13/CXCR5 axis activation

Purpose Spinal cord ischemia-reperfusion (I/R) injury is an unresolved complication and its mechanisms are still not completely understood. Here, we studied the neuroprotective effects of dexmedetomidine (DEX) postconditioning against spinal cord I/R injury in rats and explored the possible mechanisms. Materials and methods In the study, rats were randomly divided into five groups: sham group, I/R group, DEX0.5 group, DEX2.5 group, and DEX5 group. I/R injury was induced in experimental rats; 0.5 μg/kg, 2.5 μg/kg, 5 μg/kg DEX were intravenously injected upon reperfusion respectively. Neurological function, histological assessment, and the disruption of blood-spinal cord barrier (BSCB) were evaluated via the BBB scoring, hematoxylin and eosin staining, Evans Blue (EB) extravasation and spinal cord edema, respectively. Neutrophil infiltration was evaluated via Myeloperoxidase (MPO) activity. Microglia activation and reactive gliosis was evaluated via ionized calcium-binding adapter molecule-1(IBA-1) and glial fibrillary acidic protein (GFAP) immunofluorescence, respectively. The expression of C-X-C motif ligand 13 (CXCL13), C-X-C chemokine receptor type 5(CXCR5), caspase-3 was determined by western blotting. The expression levels of interleukin 6(IL-6), tumor necrosis factor-α(TNF-α), IL-1β were determined by ELISA assay. Results DEX postconditioning preserved neurological assessment scores, improved histological assessment scores, attenuated BSCB leakage after spinal cord I/R injury. Neutrophil infiltration, microglia activation and reactive gliosis were also inhibited by DEX postconditioning. The expression of CXCL13, CXCR5, caspase-3, IL-6, TNF-α, IL-1β were reduced by DEX postconditioning. Conclusions DEX postconditioning alleviated spinal cord I/R injury, which might be mediated via inhibition of neutrophil infiltration, microglia activation, reactive gliosis and CXCL13/CXCR5 axis activation.

Magnetic resonant imaging features of acute traumatic cervical spinal cord injury: Its correlation with american spinal injury association impairment scale and prediction of neurological improvement using a low tesla magnetic resonant imaging in a resource-constrained environment

Context: Traumatic spinal cord injury (TSCI) is a devastating disease, hence the need to identify clinical and radiological injury features that can predict neurological improvement. Aims: This study aims to identify magnetic resonant imaging (MRI) features in cervical TSCI that correlates with neurological status at admission, and also predict early neurological improvement. Settings and Design: This was a prospective cohort study. Subjects and Methods: Admission MRI features of 47 patients with cervical TSCI and their neurological assessments at admission and 3 months post-injury were reviewed prospectively over a period of 18 months. Correlational and regression analyses were done using SPSS® version 25 software. P < 0.05 was used as the level of significance. Results: Spinal cord oedema and cord contusion (78.0%) constitute the majority of injury patterns seen on MRI. There was a significant association between spinal cord contusion and cord oedema on MRI and incomplete TSCI. Likewise, spinal cord haemorrhage, compression and transection were associated with complete TSCI. Maximum canal compromise (MCC), maximum spinal cord compression (MSCC) and length of cord lesion significantly correlate with American Spinal Injury Association Impairment Scale at admission (P = 0.033, P = 0.015 and P < 0.001, respectively). Increasing values of these variables were found to be independent predictors of complete TSCI. However, length of cord lesion was the only independent predictor of neurological improvement, 3 months post-injury (P = 0.025). Conclusions: Spinal cord haemorrhage, compression, transection and higher values of MCC, MSCC and increased length of cord lesion were predictive of complete TSCI. However, the length of spinal cord lesion was a better predictor of early neurological improvement.

Ferulic acid improves motor function induced by spinal cord injury in rats via inhibiting neuroinflammation and apoptosis.

ABSTRACTPurposeTo investigate the effect of ferulic acid (FA) on spinal cord injury (SCI)-induced motor dysfunction and to explore the possible pharmacological mechanisms.MethodsAdult male Wistar rats were used in our study. SCI was achieved by clipping the spinal cord T9 of the rat by a vascular clip for 2 minutes. The motor function of the rat was evaluated by Basso, Beattie, and Bresnahan scoring method (BBB) and inclined plane test. Hematoxylin and eosin (HE) staining, NISSL staining, and transmission electron microscopic examination were used to evaluate alterations at the histological level. Polymerase chain reaction (PCR), Western blots, and enzyme-linked immunosorbent assays (ELISA) were employed in biochemical analysis.ResultsThe BBB score and inclined plane test score significantly decreased after SCI surgery, whereas chronic FA treatment (dose of 90 mg/kg, i.g.) for 28 days improved SCI-induced motor dysfunction. HE staining showed that SCI surgery induced internal spinal cord edema, but the structural changes of the spinal cord could be reversed by FA treatment. NISSL staining and transmission electron microscopic examination confirmed the improvement of the effect of FA on the injury site. In the biochemical analysis, it could be found that FA inhibitedSCI-induced mRNA and protein overexpression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), as well as iNOS and COX-2 via the modulation of NF-κB level in the spinal cord of SCI rat. Moreover, the SCI-induced decrease of Bcl-2/Bax ratio was also reversed by FA treatment. However, the effect of FA on the expression of Beclin-1 was not statistically significant.ConclusionsFA showed a therapeutic effect on SCI, which may be associated with the regulation of neuroinflammation and apoptosis.

Risk Factors for Hypoglycemia with the Use of Enteral Glyburide in Neurocritical Care Patients

Intravenous glyburide has demonstrated safety when used for attenuation of cerebral edema, although safety data are lacking for enteral glyburide when used for this indication. We aimed to determine the prevalence of and risk factors for hypoglycemia in neurocritical care patients receiving enteral glyburide. We performed a retrospective case-control chart review (hypoglycemia vs. no hypoglycemia) of adult patients who received enteral glyburide for prevention or treatment of cerebral or spinal cord edema. Hypoglycemia was defined as a blood glucose <55.8 mg/dL. Descriptive statistics were used, with multivariate analysis to measure the association of risk factors and outcomes. Logistic regression was applied to outcomes with an exposure. Potential confounders were evaluated using the t-test or the Wilcoxon rank-sum test for continuous variables, and the χ2 test or the Fisher exact test for categorical variables. Seventy-one patients (60.6% men, median age 60 years) were included. The majority received 2.5 mg of enteral glyburide twice daily. Diagnoses included tumors (35.2%), intracerebral hemorrhage (28.2%), postspinal surgery (12.7%), and ischemic stroke (12.7%). Hypoglycemia occurred in 17 (23.9%) patients. Multivariate analysis identified admission serum creatinine (odds ratio, 27.2; [1.661, 445.3]; P < 0.05) as a risk factor for hypoglycemia, whereas body mass index >30 (odds ratio, 0.085; [0.008, 0.921]; P < 0.05) was protective. Hypoglycemic episodes are common following enteral glyburide in neurocritical care patients. Both patients with and without diabetes mellitus are at risk of hypoglycemia. Elevated admission serum creatinine may increase the risk of hypoglycemia when utilizing glyburide for prevention or treatment of cerebral or spinal cord edema.

Development of pre-syrinx state and syringomyelia following a minor injury: a case report

BackgroundA generally accepted rule is that posttraumatic syringomyelia (PTS) results from spinal cord injury (SCI).Case presentationHere, we report the development of syringomyelia without SCI in a 54-year-old Caucasian man following a mild motor vehicle accident. The computed tomography on admission excluded an injury of the spine. Because of neck and back pain, magnetic resonance imaging was performed on day 3 post-injury and demonstrated minimal changes from a ligamentous strain at the cervicothoracic transition. Any traumatic affection of the bone, vertebral discs, intraspinal compartment, or spinal cord were excluded. Some limb weakness and neurogenic bladder dysfunction started manifesting within the following weeks. Repeated MRIs following the accident demonstrated arachnoid adhesions at the C1–2 level and spinal cord edema equivalent to a pre-syrinx state at 12 months and syrinx formation at 24 months. Because of further deterioration, decompression was performed at 36 months.ConclusionsWe conclude that even after a minor trauma PTS can occur and that medullary edema (pre-syrinx state) may precede syrinx formation.

Foix-Alajouanine Syndrome Mimicking Longitudinally Extensive Transverse Myelitis.

Spinodural arteriovenous fistula (SDAF) can present with longitudinally extensive transverse myelitis (LETM), progressive gait instability, and lower extremity weakness.Failure to promptly recognize this condition and misdiagnosis can result in a poor outcome.Microsurgical obliteration of the SDAF provides better results than embolization.

A Case of Pancoast Syndrome Caused By an Extramedullary Plasmacytoma in Relapsed Multiple Myeloma

Extramedullary plasmacytomas are present in 7-18% of multiple myeloma at diagnosis, and up to 13-20% at the time of disease relapse. (Blade J et al., 2011; Varettoni M et al., 2010) A case series in 2010 with 1003 patients found involvement of soft tissues surrounding the axial skeleton in 85% of cases at diagnosis, and 72% of cases at time of relapse. Other sites of involvement included lymph nodes, liver, kidney, airways, skin, breast, and the gastrointestinal tract. (Varettoni M et al., 2010) An extramedullary plasmacytoma leading to Pancoast syndrome has been reported only 3 times in previous literature, in 1979, 1983, and 1984. (Brenner B et al., 1984; Chen KT et al., 1983; Wilson KS et al., 1979) A case of this uncommon presentation is reported here. The patient is a 70-year-old male with a diagnosis of ISS-3 IgG Kappa multiple myeloma (serum monoclonal protein 10 g/L, Kappa light chain 2356.29 mg/L, free light chain ratio 386.28, bone marrow biopsy 61.8% plasma cells) the year prior to the current presentation. He was not a candidate for autologous stem cell transplant due to poor pulmonary function, and hence had a treatment plan for 9 cycles of cyclophosphamide/bortezomib/dexamethasone (CyBorD), of which 6 were completed. Treatment was then stopped due to a macrocytic hypoproliferative anemia thought to be related to early hypoplasia from prior CyBorD. At this time, he was in complete remission with bone marrow biopsy showing 2.8% plasma cells. His medical history was otherwise significant for coronary artery disease with prior myocardial infarction, previous transient ischemic attack with carotid stenosis and carotid endarterectomy, hypertension, dyslipidemia, spinal stenosis with multilevel degenerative changes most pronounced at L3-4, and osteoarthritis. He had a 30 pack-year smoking history, and continued to smoke cigars. The patient presented to hospital 5 months after completion of the above therapy with 2 weeks of right shoulder pain radiating down the arm, and right hand weakness, numbness, and tingling. He had also noted right lower extremity weakness and numbness with some incontinence. The physical exam was significant for right ptosis and myosis (Figure 1), decreased strength and sensation in the right C8-T1 distribution, inability to lift the right lower extremity off the bed, reduced anal sphincter tone, and a post-void residual volume of 700 mL. CT brain and cervical spine showed new abnormal mass-like tissue within the right hemithorax apical region with apparent extension into the cervicothoracic junction. Given his history of multiple myeloma as well as his smoking history, the mass was thought to either be a primary lung malignancy, or an extramedullary plasmacytoma. The patient was therefore admitted for ongoing management and diagnostic work-up. He was seen by the inpatient Hematology service, and noted to have progression of his multiple myeloma with Kappa light chain 885.99 mg/L (free light chain ratio 48.67). He was started on pulse steroids with a plan for daratumumab/lenalidomide/dexamethasone (DRd) with dose reduction of the lenalidomide given his prior history of myelosuppression. Further imaging with MR entire spine showed the right lung apical soft tissue mass extending into the epidural space from C7-T2 with severe spinal cord compression and spinal cord edema (Figure 2), as well as epidural extension of disease at L5 resulting in moderate spinal canal stenosis. The patient was then seen by Radiation Oncology and received 8 Gy as a single fraction to the apical lung mass. Subsequent biopsy of the mass showed a plasma cell neoplasm, Kappa restricted by in-situ hybridization, and compatible with a plasmacytoma. The patient then received two cycles of DRd and thought to be in very good partial response with Kappa light chain 32 mg/L, free light chain ratio 3.8, and resolution of previous apical lung mass and L5 epidural extension on subsequent MR spine. We document here a rare case of plasmacytoma leading to Pancoast syndrome. Given the difference in therapeutic options and prognosis between an extramedullary plasmacytoma and a primary lung malignancy, it is important to recognize this presentation as a diagnostic possibility, and to pursue relevant investigation and targeted management for the same. Disclosures Sharma: Enstasis therapeutics: Current equity holder in private company; Pfizer: Current equity holder in private company; Gilead: Other: shareholder; Contrafect corporation: Current equity holder in private company; Moderna: Other: shareholder.

Syringomyelia Associated with Spinal Dural Arteriovenous Fistula: Clinical and Radiological Improvement after Embolization

Spinal dural arteriovenous fistulae (AVF) are rare and can result in spinal cord dysfunction. We present one such case wherein the patient presented with a venous congestive myelopathy. Magnetic resonance imaging showed a syrinx formation, spinal cord edema, and flow voids. Digital subtraction angiography confirmed the dural AVF, which was treated with embolization. The syrinx disappeared, other spinal cord changes improved, and the patient had remarkable clinical improvement. The case is presented to draw attention to the rare formation of a syrinx in a spinal dural arteriovenous fistula and its disappearance after successful embolization.

Save Your Maximum Tolerated Dose: How to Diagnose Procedure-Related Spinal Cord Lesions After Lumbar Intrathecal Bolus Administration of Oligonucleotides in Cynomolgus Monkeys.

Many potential drugs for treatment of neurodegenerative diseases, particularly antisense oligonucleotides (ASOs), are administered via lumbar intrathecal injection, because these drugs do not cross the blood-brain barrier. Intrathecal injection is a well-established method in cynomolgus monkeys, a species that is used in preclinical safety assessment when other nonrodent species cannot be used. The authors completed intrathecal ASO administration in over 30 preclinical safety studies (>1000 animals and >4500 dose administrations) during which we observed 3 cases of procedure-related spinal cord necrosis (incidence <0.1%). We describe clinical symptoms, diagnostic approaches, morphological features, and prognosis of this rare injury, and compare these findings with typical drug-related findings of ASOs dosed by intrathecal injection. The low incidence of procedure-related and dose-limiting lesions confines this analysis to a small sample set. The pattern of effects is similar across all monkeys despite differences in age, body weight, and intrathecal injection site. All 3 cases presented a combination of the following findings: blood in cerebrospinal fluid at time of injection, clinical signs that increase in severity within a day of dosing, lameness of both hind limbs, reduced muscle tone, and loss of patellar, foot grip, and/or anal reflexes. In all cases, magnetic resonance imaging (MRI) showed a linear hyperintense lesion in the lumbar spinal cord. In 2 cases, this hyperintensity was associated with evidence of spinal cord edema. We conclude that a pattern of in-life and pathology findings, including noninvasive MRI assessment, is indicative of procedure-related effects.

Implantable Osmotic Transport Device Can Reduce Edema After Severe Contusion Spinal Cord Injury

Recent findings from the ISCoPe study indicate that, after severe contusion to the spinal cord, edema originating in the spinal cord accumulates and compresses the tissue against the surrounding dura mater, despite decompressive laminectomy. It is hypothesized that this compression results in restricted flow of cerebrospinal fluid (CSF) in the subarachnoid space and central canal and ultimately collapses local vasculature, exacerbating ischemia and secondary injury. Here we developed a surgically mounted osmotic transport device (OTD) that rests on the dura and can osmotically remove excess fluid at the injury site. Tests were performed in 4-h studies immediately following severe (250 kD) contusion at T8 in rats using the OTD. A 3-h treatment with the OTD after 1-h post injury significantly reduced spinal cord edema compared to injured controls. A first approximation mathematical interpretation implies that this modest reduction in edema may be significant enough to relieve compression of local vasculature and restore flow of CSF in the region. In addition, we determined the progression of edema up to 28 days after insult in the rat for the same injury model. Results showed peak edema at 72 h. These preliminary results suggest that incorporating the OTD to operate continuously at the site of injury throughout the critical period of edema progression, the device may significantly improve recovery following contusion spinal cord injury.

Mannitol Reduces Spinal Cord Edema in Rats with Acute Traumatic Spinal Cord Injury

Background: The research about anti-edema effects of mannitol on acute traumatic spinal cord injury (SCI) in rats is rare. Objective: This study aimed to explore the effect of mannitol on spinal cord edema after SCI in rats. Methods: Seventy-eight adult female rats were assigned to three groups randomly: a sham control group (n = 18), a contusion and normal saline contrast group (n=30), and a contusion and mannitol treatment group (n=30). We used the open-field test to estimate the functional recovery of rats weekly. Spinal cord water content was measured to determine the spinal cord edema. The ultrastructure features of the injured dorsolateral spinal cord were determined on the 7th day after SCI by HE staining. Results: The mannitol group had greatly improved Basso-Beattie-Bresnahan (BBB) scores when compared with the saline contrast group. The spinal cord water content was increased significantly after SCI, and there was no significant difference in the water content between the NaCl and mannitol groups 1 day after SCI. The water content at 3 and 7 days after SCI was significantly lower in the mannitol group than in the NaCl group (p &lt; 0.05). Mannitol can reduce spinal cord edema by increasing the number of red blood cells in the injured spinal cord and decrease the ratio (dorsoventral diameter/ mediolateral diameter) of spinal cord 7 days post-SCI. Conclusion: Mannitol increases recovery of motor function in rats, reduces spinal cord edema and increases the number of red blood cells in the injured spinal cord, decreasing the ratio of spinal cord to reduce pressure.

Spinal Cord Infarction after Transcatheter Embolization of Pelvic Arteriovenous Malformation.

An 80-year-old woman presented with abdominal and right lower limb pain. Radiological examination revealed pelvic arteriovenous malformations (pAVMs). Although transarterial embolization was repeated, dilation of the common iliac vein worsened. Four sessions of embolization were performed for the internal iliac vein. Paraplegia gradually occurred a day after the final procedure. Magnetic resonance imaging revealed thoracic spinal cord edema and paraspinal vasodilatation, suggesting spinal cord infarction. Additional angiography revealed a radiculomedullary vein draining into the spinal canal from the pAVM; hence, surgical interruption was performed. Incomplete venous embolization of the pAVM caused spinal cord congestion and infarction.

Ischemic damage may play an important role in spinal cord injury during dancing

Study designRetrospective analysis.SettingChina Rehabilitation Research Center, Beijing, China.ObjectiveTo explore possible mechanisms underlying spinal cord injury (SCI) in children caused by hyperextension of the spine while dancing.MethodsThe clinical records of 88 children with SCI (mean age, 5.97 years; age range, 4–10 years) admitted to our hospital from January 1989 to October 2019 were retrospectively reviewed. Computed tomography and magnetic resonance imaging were performed on the day of injury. The time from injury to development of paralysis, as well as post-injury activities were surveyed, while abnormal patterns on images, the range of the involved vertebrae, and the extents of edema and atrophy were assessed.ResultsAmong the 88 patients, 6 (6.8%) were unable to move immediately after SCI, while paralysis occurred in 42, 23, and 17 patients at <30, 30–60, and >60 min after SCI, respectively. The neurological level of injury of 84 patients was between T4 and T12. On sagittal T2-weighted images (T2WIs), the longitudinal range of spinal cord edema was more than one vertebral body in 65 patients, while spinal cord atrophy below T8 was found in 40 patients. On axial T2WIs, although three patients had none, long T2 signals were found in the central gray matter of seven patients. Meanwhile, necrosis of the central area combined with the peripheral white matter was observed in 57 patients, while three patients had total involvement on a cross section.ConclusionIschemia-related damage, rather than direct trauma to the spinal cord, may play an important role in SCI due to spinal hyperextension during dancing.

Outcomes of occipitocervical fixation using a spinous process screw in C2 as a third anchor point for occipitocervical fixation: a case presentation

BackgroundPosterior occipitocervical fixation and fusion are often required to address occipitocervical instability. Safe, stable internal fixation with screws is vital for the success of such surgery. Thus, poor selection of an internal fixation technique may cause fixation and fusion failure, possibly leading to neurovascular injury. Hence, in certain cases, such as in patients with severe instability of an occipitocervical deformity or osteoporosis, we hypothesized that having a third anchor point (a screw in C2) could enhance the stability of the occipitocervical fixation.Case presentationA 31-year-old man with occipitocervical deformity and spinal cord edema underwent a traditional occipitocervical fixation procedure but with the addition of a spinous process screw in C2 as a third anchor point. The procedure included posterior internal fixation and fusion. The occipitocervical fixation was completed by inserting occipital screws, bilateral C2 pedicle screws, C3 lateral mass screws, and a spinous process screw in C2 as a third anchor point. There were no neurovascular complications or incision-site infections. Postoperatively, radiography and computed tomography showed that the occipitocervical reduction and internal fixation had resulted in good spinal alignment, and magnetic resonance imaging showed no obvious spinal cord compression. At 4 months after the surgery, fusion was observed, and the occipitocervical screws remained well positioned. The patient continued to be monitored for 24 months postoperatively. At the 24-month follow-up visit, the muscle strength of the limbs was grade 5, and the patient’s sensation function had improved over his preoperative condition.ConclusionsUse of a C2 spinous process screw as a third anchor point may enhance the stability of occipitocervical fixation. Further biomechanical and clinical studies are needed to validate this result.

Role of Magnetic Resonance Imaging in Spinal Cord Traumatic Injuries and its outcome according to ASIA Impairment Scale

Background:&nbsp; Spinal trauma is one of common neurosurgical problem and mismanagement can lead to fatal outcome. Objective: To determine the MRI based initial diagnosis of acute spinal injuries and determine its pattern with reference to its neurological outcome. Methodology: Study Design: Prospective cohort study, involving radiographic and clinical review. This study was performed on 69 patients of spinal trauma, January to December, 2018, at Department of Radiology, Gujranwala Medical College and DHQ teaching Hospital, Gujranwala. &nbsp;Male and female of any age were included. After initial neurological examination these patients undergone &nbsp;for &nbsp;Magnetic Resonance Imaging&nbsp; of spine, which &nbsp;were analyzed and correlated with American Spinal Injury Association (ASIA) impairment scale (AIS), then subsequently at sub-acute interval to assess neurological outcome. Data analysis was done on SPSS version 17. Results: The most common MRI findings were spinal cord edema 24 cases (34.7%). Among the other findings were, cord contusion 17 cases (24.6%), spinal cord deformity due to extrinsic compression 14 cases (20.2%), focus of hemorrhage within the cord 9 cases (13%), epidural hematoma 3cases (4.3%) and few cases appeared normal cord 2 cases (2.3%). Most of the MRI findings correlated with clinical presentation of the patient according to American Spinal Injury Association (ASIA) impairment scale. Conclusion: Patients with initial hemorrhagic grade had very poor prognosis, whereas those with focal spinal cord edema had good clinical recovery.

Exogenous activation of cannabinoid-2 receptor modulates TLR4/MMP9 expression in a spinal cord ischemia reperfusion rat model

BackgroundCannabinoid-2 receptor (CB2R) plays an important role in the cascading inflammation following ischemic injury. The toll-like receptors 4 (TLR4)/matrix metalloproteinase 9 (MMP9) signal pathway is involved in blood-brain barrier dysfunction induced by ischemia stroke. The aim of this study is to investigate the roles of exogenous activation of CB2R on attenuating neurological deficit and blood-spinal cord barrier (BSCB) disruption during rat spinal cord ischemia reperfusion (I/R) injury, through modulation of the TLR4/MMP9 axis.MethodsAnimals were intraperitoneally pretreated with TLR4 inhibitor TAK-242, CB2R agonist JWH-133 with or without CB2R antagonist AM630, or equivalent volume of vehicle 1 h before undergoing 14-min occlusion of descending aorta or sham operation. One, two, three, and 7 days after reperfusion, hindlimb locomotor function was evaluated with Basso, Beattie, and Bresnahan (BBB) Locomotor Scale, BSCB integrity was detected by measurement of Evans blue (EB) extravasation and spinal cord edema. The protein expression levels of CB2R, tight junction protein Zonula occluden-1 (ZO-1), TLR4, MMP9, MyD88, NF-κB p65, and NF-κB p-p65 were determined by western blot. The MMP9 activity was analyzed by gelatin zymography. Double immunofluorescence staining was used to identify the perivascular localization of CB2R, TLR4, MMP9, and reactive astrocytes, as well as the colocalization of CB2R, TLR4, and MMP9 with reactive astrocytes.ResultsJWH-133 pretreatment attenuated hindlimb motor functional deficit and BSCB leakage, along with preventing downregulation of ZO-1 and upregulation of TLR4/MMP9, similar to the effects of TAK-242 preconditioning. JWH-133 or TAK-242 pretreatment reduced the perivascular expression of TLR4/MMP9 and reactive astrocytes following injury. JWH-133 pretreatment also downregulated MyD88/NF-κB level, MMP9 activity, and the astrocytic TLR4/MMP9 after I/R injury.ConclusionsExogenous activation of CB2R by JWH-133 attenuated neurological deficit and BSCB disruption after spinal cord I/R injury via inhibition of TLR4/MMP9 expression.

Prolonged inflammation leads to ongoing damage after spinal cord injury

The pathogenesis of spinal cord injury (SCI) remains poorly understood and treatment remains limited. Emerging evidence indicates that post-SCI inflammation is severe but the role of reactive astrogliosis not well understood given its implication in ongoing inflammation as damaging or neuroprotective. We have completed an extensive systematic study with MRI, histopathology, proteomics and ELISA analyses designed to further define the severe protracted and damaging inflammation after SCI in a rat model. We have identified 3 distinct phases of SCI: acute (first 2 days), inflammatory (starting day 3) and resolution (>3 months) in 16 weeks follow up. Actively phagocytizing, CD68+/CD163- macrophages infiltrate myelin-rich necrotic areas converting them into cavities of injury (COI) when deep in the spinal cord. Alternatively, superficial SCI areas are infiltrated by granulomatous tissue, or arachnoiditis where glial cells are obliterated. In the COI, CD68+/CD163- macrophage numbers reach a maximum in the first 4 weeks and then decline. Myelin phagocytosis is present at 16 weeks indicating ongoing inflammatory damage. The COI and arachnoiditis are defined by a wall of progressively hypertrophied astrocytes. MR imaging indicates persistent spinal cord edema that is linked to the severity of inflammation. Microhemorrhages in the spinal cord around the lesion are eliminated, presumably by reactive astrocytes within the first week post-injury. Acutely increased levels of TNF-alpha, IL-1beta, IFN-gamma and other pro-inflammatory cytokines, chemokines and proteases decrease and anti-inflammatory cytokines increase in later phases. In this study we elucidated a number of fundamental mechanisms in pathogenesis of SCI and have demonstrated a close association between progressive astrogliosis and reduction in the severity of inflammation.

MCC950, a Selective Inhibitor of NLRP3 Inflammasome, Reduces the Inflammatory Response and Improves Neurological Outcomes in Mice Model of Spinal Cord Injury.

Spinal cord injury (SCI) is a serious condition that affects bodily function; however, there is no effective therapy in clinical practice. MCC950, a selective NOD-like receptor protein-3 (NLRP3) inflammasome inhibitor, has been reported to alleviate canonical and non-canonical NLRP3 inflammasome activation of the inflammatory response in vitro and in vivo. However, the effect of MCC950 treatment on neurological post-SCI recovery remains unclear. In this study, we assessed the pharmacological effect of MCC950 on an experimental SCI model in vivo and neuronal injury in vitro. We found that MCC950 improved the grip strength, hind limb movements, spinal cord edema, and pathological injury in the SCI mice. We demonstrated that it exerted this effect by blocking NLRP3 inflammasome assembly, including NLRP3-ASC and NLRP3-Caspase-1 complexes, as well as the release of pro-inflammatory cytokines TNF-α, IL-1β, and IL-18. Moreover, we found that MCC950 reduced spinal neuron injury and NLRP3 inflammasome activation, which had been induced by oxygen–glucose deprivation (OGD) or lipopolysaccharides (LPS) in vitro. In conclusion, our findings indicate that MCC950 alleviates inflammatory response and improves functional recovery in the acute mice model of SCI by blocking NLRP3 inflammasome assembly and alleviating downstream neuroinflammation. Therefore, these findings could prove useful in the development of effective therapeutic strategies for the treatment and prognosis of SCI.

Lumbar 4-5 Laminoplasty for Ligation of Dural Fistula: 2-Dimensional Operative Video.

The goal of treatment for spinal dural arteriovenous fistulas is disconnection of the fistulous point to eliminate venous congestion-associated hypoperfusion and mass effect. The nidus can be surgically excised or disconnected from the arterial feeder just proximal to the dilated venous plexus. This patient had a filus terminale dural arteriovenous fistula. The patient had multiple findings of myelopathy, which prompted the imaging evaluation that revealed prominent flow voids and significant caudal thoracic spinal cord edema. Preoperative digital subtraction angiography demonstrated a fistulous point at the lumbar 4 level. A lumbar 4 and lumbar 5 laminoplasty was performed for spinal canal access. Following achievement of intradural access, exploration was performed, augmented by indocyanine green fluoroscopy. The filum terminale was then transected, and the fistula was then completely excised to achieve surgical cure. Following the procedure, the patient's myelopathy improved, and she regained ambulatory status. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.

Extensive Epidural Steatitis and Epaxial Myositis Associated with Intramuscular Injection of Melarsomine Dihydrochloride in Two Dogs

AbstractThis is a retrospective case series in which clinicopathological and imaging findings associated with neurological complications secondary to melarsomine dihydrochloride administration are reported in two dogs with Dirofilaria immitis infection. Following intramuscular injection of melarsomine dihydrochloride based on manufacturers' guidelines, two dogs developed acute, progressive, nonambulatory paraparesis or paraplegia. Magnetic resonance imaging was suggestive of epidural steatitis, resulting in compression of the spinal cord and spinal cord oedema. In one dog, emphysematous myositis throughout the lumbar paravertebral muscles was present. Hemilaminectomy with the intent of achieving spinal cord decompression and obtaining specimens for microbiological and histopathological evaluation was performed in both dogs. One dog partially regained function postoperatively whereas the other was euthanatized intraoperatively. Histologically, epidural steatitis was observed in the surviving dog and epidural steatitis, myonecrosis and grey and white matter changes in the spinal cord were observed in the euthanatized dog. Microbiological testing failed to identify bacteria from the affected tissues. Both cases highlight the potential for the development of extensive epidural steatitis and consequent spinal cord compression following intramuscular administration of melarsomine dihydrochloride. Further investigation into the optimal therapeutic intervention in dogs experiencing neurological complications following melarsomine administration is warranted.