E8002 Reduces Adhesion Formation and Improves Joint Mobility in a Rat Model of Knee Arthrofibrosis.

Knee arthrofibrosis is a common complication of knee surgery, caused by excessive scar tissue, which results in functional disability. However, no curative treatment has been established. E8002 is an anti-adhesion material that contains L-ascorbic acid, an antioxidant. We aimed to evaluate the efficacy of E8002 for the prevention of knee arthrofibrosis in a rat model, comprising injury to the surface of the femur and quadriceps muscle 1 cm proximal to the patella. Sixteen male, 8-week-old Sprague Dawley rats were studied: in the Adhesion group, haemorrhagic injury was induced to the quadriceps and bone, and in the E8002 group, an adhesion-preventing film was implanted between the quadriceps and femur after injury. Six weeks following injury, the restriction of knee flexion owing to fibrotic scarring had not worsened in the E8002 group but had worsened in the Adhesion group. The area of fibrotic scarring was smaller in the E8002 group than in the Adhesion group (p < 0.05). In addition, the numbers of fibroblasts (p < 0.05) and myofibroblasts (p < 0.01) in the fibrotic scar were lower in the E8002 group. Thus, E8002 reduces myofibroblast proliferation and fibrotic scar formation and improves the range of motion of the joint in a model of knee injury.

E8002 Inhibits Peripheral Nerve Adhesion by Enhancing Fibrinolysis of l-Ascorbic Acid in a Rat Sciatic Nerve Model.

Perineural adhesions leading to neuropathy are one of the most undesirable consequences of peripheral nerve surgery. However, there are currently no widely used compounds with anti-adhesive effects in the field of peripheral nerve surgery. E8002 is a novel, anti-adhesive, multi-layer membrane that contains L-ascorbic acid (AA). Here, we investigated the effect and mechanism of E8002 in a rat sciatic nerve adhesion model. A total of 21 rats were used. Six weeks after surgery, macroscopic adhesion scores were significantly lower in the E8002 group (adhesion procedure followed by nerve wrapping with E8002) compared to the E8002 AA(-) group (adhesion procedure followed by nerve wrapping with the E8002 membrane excluding AA) and adhesion group (adhesion procedure but no treatment). Correspondingly, a microscopic examination revealed prominent scar tissue in the E8002 AA(-) and adhesion groups. Furthermore, an in vitro study using human blood samples showed that AA enhanced tissue-type, plasminogen activator-mediated fibrinolysis. Altogether, these results suggest that E8002 may exert an anti-adhesive action via AA and the regulation of fibrinolysis.

Application of a Novel Anti-Adhesive Membrane, E8002, in a Rat Laminectomy Model.

Neuropathic pain after spinal surgery, so-called failed back surgery syndrome, is a frequently observed common complication. One cause of the pain is scar tissue formation, observed as post-surgical epidural adhesions. These adhesions may compress surrounding spinal nerves, resulting in pain, even after successful spinal surgery. E8002 is an anti-adhesive membrane. In Japan, a clinical trial of E8002 is currently ongoing in patients undergoing abdominal surgery. However, animal experiments have not been performed for E8002 in spinal surgery. We assessed the anti-adhesive effect of E8002 in a rat laminectomy model. The dura matter was covered with an E8002 membrane or left uncovered as a control. Neurological evaluations and histopathological findings were compared at six weeks postoperatively. Histopathological analyses were performed by hematoxylin⁻eosin and aldehyde fuchsin-Masson Goldner staining. Three assessment areas were selected at the middle and margins of the laminectomy sites, and the numbers of fibroblasts and inflammatory cells were counted. Blinded histopathological evaluation revealed that adhesions and scar formation were reduced in the E8002 group compared with the control group. The E8002 group had significantly lower numbers of fibroblasts and inflammatory cells than the control group. The present results indicate that E8002 can prevent epidural scar adhesions after laminectomy.

Acquired Simple Bone Cyst Associated With Lumbar Spinal Canal Stenosis Progression: A Case Report.

A simple bone cyst (SBC) in the posterior lumbar bone structure is very rare. Here, we report a case of SBC at the L5 lumbar lamina with venous obstruction associated with ligamentum flavum thickening. A 59-year-old woman presented with intermittent claudication due to low back pain and bilateral sciatica. A lumbar MRI showed L4-5 lumbar spinal canal stenosis and a T2-weighted image hyperintense lesion in the L5 lamina. Imaging four years earlier showed no lesions in the L5 lamina. Her symptoms improved after lumbar decompression surgery. The L5 lamina lesion was SBC, leading to a diagnosis of venous infarction. The involvement of neovascularization in the mechanism of degenerative hypertrophy in the ligamentum flavum was suggested. In this case, increased venous perfusion and venous obstruction were involved in the formation of the bone cyst.

Intractable hiccup caused by syrinx in Chiari type I malformation. Two cases report.

Background: Intractable hiccups (IH) due to syringomyelia or syringomyelia/syringobulbia associated with Chiari type I malformations (CMI) are extremely rare. Here, we present two patients who presented with IH; one had a CMI with syringomyelia/syringobulbia, and the other, with CMI and syringomyelia. Case Description: The first patient was an 18-year-old female who presented with IH attributed to a holocord syrinx and syringobulbia involving the right dorsolateral medulla. The second patient was a 22-year-old female with a C3-5 syringomyelia. Both patients successfully underwent foramen magnum decompressions that improved their symptoms, while subsequent magnetic resonance studies confirmed shrinkage of their syringobulbia/syringomyelia cavities. Conclusion: IH was due to cervical syringomyelia/syringobulbia in one patient and cervical syringomyelia in the other; both were successfully managed with foramen magnum decompressions.

Intramedullary Schwannoma of the Spinal Cord: A Nationwide Analysis by the Neurospinal Society of Japan.

OBJECTIVE: This study was aimed to report the clinical characteristics of intramedullary schwannomas and discuss imaging findings and treatment strategies. METHODS: The inclusion criterion was consecutive patients with intramedullary schwannomas who were surgically treated at 8 centers between 2009 and 2020. Clinical characteristics included age, sex, clinical presentation, disease duration, and follow-up period. The modified McCormick scale was used to compare the preoperative and postoperative conditions. Pre- and postoperative magnetic resonance images (MRI) of each case were analyzed. RESULTS: The mean age of the total 11 patients at the operation was 50.2 years. The mean duration of the symptoms was 23 months, with limb paresthesia being the most common clinical presentation. The cervical spine was the most common localization level of the tumor in 6 cases. The mean follow-up duration was 49.4 months. Gross total resection (GTR) and subtotal resection (STR) was achieved in 9 and 2 cases, respectively. According to the modified McCormick scale at 6 months postoperatively, 7 cases (63.6%) had improved and 4 cases (36.3%) had unchanged grades. Typical MRI findings of the intramedullary schwannoma included ring-like enhancement, syringomyelia, cystic formation, intramedullary edema, and hemosiderin deposition. Gadolinium enhancement was homogenous in 8 cases (72.7%). The tumor margins were well demarcated in all cases. CONCLUSION: Intramedullary schwannoma should be considered when sharp margins and well-enhanced tumors are present at the cervical spine level and the initial symptoms are relatively mild, such as dysesthesia. When GTR cannot be achieved, STR for tumor decompression is recommended.

Clinical neuroprotective drugs for treatment and prevention of stroke.

Stroke is an enormous public health problem with an imperative need for more effective therapies. In therapies for ischemic stroke, tissue plasminogen activators, antiplatelet agents and anticoagulants are used mainly for their antithrombotic effects. However, free radical scavengers, minocycline and growth factors have shown neuroprotective effects in the treatment of stroke, while antihypertensive drugs, lipid-lowering drugs and hypoglycemic drugs have shown beneficial effects for the prevention of stroke. In the present review, we evaluate the treatment and prevention of stroke in light of clinical studies and discuss new anti-stroke effects other than the main effects of drugs, focusing on optimal pharmacotherapy.

Case of lumbar ligamentum flavum hematoma with epidural hematoma resulting in cauda equina compression.

Background: Lumbar ligamentum flavum hematomas (LFHs) are rare. However, when they occur and contribute to epidural cauda equina compression, timely surgical intervention is frequently warranted. Case Description: A 69-year-old female presented with the left lower extremity sciatica and gait disturbance of 2 weeks' duration that ultimately evolved into a paraparesis/cauda equina syndrome. When the lumbar MRI revealed left-sided L4-L5 epidural compression attributed to a hemorrhage into the hypertrophied ligamentum flavum (HLF), she successfully underwent a bilateral fenestration/decompressive procedure. Pathologically, neovascularization and rupture of the ventral layers of the degenerated and thickened HLF contributed to the LFH. Conclusion: Arterial neovascularization (i.e., arterial feeding vessels from paramuscular/prelaminar lumbar branches) contributed to a left-sided L4-L5 LFH that resulted in epidural cauda equina compression in a 69-year-old female. Following surgical focal fenestration/decompression, the patient's symptoms/signs resolved.

A case of mid-thoracic osteoporotic vertebral fracture with the inability to belch syndrome.

Background: Osteoporotic vertebral fractures (OVF) commonly occur at the thoracolumbar junction, but are less frequently encountered in the mid-thoracic region. Here, a 69-year-old female presented with back pain and the new onset of symptoms characterized by the inability to belch. Case Description: A 69-year-old female presented with back pain. 2 months later, she developed anorexia and difficulty belching. The thoracic magnetic resonance (MR) demonstrated a T7 OVF. As she ultimately underwent a balloon kyphoplasty (BKP), as conservative treatment was unsuccessful. Conclusion: OVF should be suspected in elderly females with the inability to belch accompanied by chest and back pain. The diagnosis is best established with a spinal MR imaging and should be followed by BKP.

A case of nonrheumatoid retro-odontoid pseudotumor in Klippel-Feil syndrome with C1 occipitalization.

Background: Patients with both nonrheumatoid retro-odontoid pseudotumors (ROPTs) and congenital craniocervical junction (CCJ) abnormalities are rare. Here, a 73-year-old female presented with neck pain and myelopathy due to MR-documented ROPT with intramedullary hyperintensity at the CCJ warranting an occipital-cervical fusion. Case Description: A 73-year-old female originally developed occipitalgia and became quadriparetic within the subsequent 7 months. The cervical MR showed a ROPT with intramedullary hyperintensity at the CCJ. Further, the CT demonstrated C1 occipitalization and a congenital C2-3 fusion without radiological instability. After she underwent an occipito-C2 fusion, her symptoms improved. Conclusion: For patients with C1 occipitalization and a Klippel-Feil syndrome, ROPT may occur due to loading of C1-2 complex. These patients typically favorably respond to occipito-C2 fusion.

Cerebrospinal fluid shunt for normal pressure hydrocephalus patient exacerbates cord symptoms due to spinal tumor.

Background: Normal-pressure hydrocephalus (NPH) and spinal intradural extramedullary benign tumors rarely exist together. Here, a 72-year-old female who presented with NPH symptoms (i.e., gait disturbance and dementia) newly developed symptoms of spinal cord compression attributed to a previously undiagnosed schwannoma. Case Description: A 72-year-old female was diagnosed with NPH without disproportionately enlarged subarachnoid space hydrocephalus. The lumbar puncture revealed an elevated cerebrospinal fluid (CSF) protein level of 0.141 g/dl, but with normal pressure. The patient's NPH symptoms improved after lumbar-peritoneal shunt placement. However, a year later, she subacutely developed a progressive Brown-Sequard syndrome. On the cervical magnetic resonance (MR), an intradural extramedullary lesion was found at the C5-C6 level which at surgery, proved to be a schwannoma. A review of this patient and three others with NPH and intradural extramedullary benign tumors revealed that 4.3 months following CSF shunting for NPH, they developed rapidly progressive cord deficits, attributed to their benign spinal tumors. Conclusion: Before the placement of shunts for NPH, patients should undergo holospinal MR imaging studies to rule out attendant spinal intradural extramedullary tumors.

Factors Associated with Rapidly Deteriorating Myelopathy in Patients with Spinal Arteriovenous Shunts.

Spinal arteriovenous (AV) shunts are rare conditions that sometimes present with myelopathy symptoms. The progression of the symptoms is usually gradual; however, some cases show rapid deterioration. We retrospectively investigated the factors that induced the rapid deterioration of myelopathy symptoms in patients with spinal AV shunts. We treated 33 patients with myelopathy with spinal AV shunts at our institutions, eight of whom experienced rapid deterioration (within 24 hours: 24.2%). Of these, three were related to the body movement or particular postures associated with playing golf, 30 minutes of Japanese straight sitting, and massage care. One patient showed deterioration after embolization for a tracheal aneurysm. The remaining four patients received steroid pulse therapy (high-dose steroid infusion) shortly before the rapid deterioration. These symptoms stopped progressing after cessation of steroid use. While positional or physical factors contributing to myelopathy deterioration might exist, we could not identify specific factors in this study. Nevertheless, rapid deterioration was frequently observed after high-dose steroid use. We must take care not to administer high-dose steroids for myelopathy caused by spinal AV shunt disease.

Guideline for management and treatment of fetal and congenital hydrocephalus: Center Of Excellence-Fetal and Congenital Hydrocephalus Top 10 Japan Guideline 2011.

INTRODUCTION: Hydrocephalus does not indicate a single clinical entity, but includes a variety of clinicopathological conditions caused by excessive cerebrospinal fluid (CSF) based on the disturbed circulation. Recent progress in prenatal neuroimagings such as MRI and ultrasound echoencephalography on fetus enables to understand clinicopathological conditions of CSF circulation disorder in conjunction with morphological changes in the central nervous system properly. It has been revealed that the CSF dynamics develop in the theory of evolution from the immature brain, as in the animals with the minor CSF pathway predominance, towards matured adult human brain together with the completion of the major CSF pathway: the "Evolution Theory in CSF Dynamics". Now, we can analyze CSF circulation dynamically and also analyze the flow velocity and direction of CSF movement. CENTER OF EXCELLENCE-FETAL HYDROCEPHALUS TOP 10 JAPAN: Along with this technical improvement, the standards of clinicopathological evaluation of hydrocephalus as well as the classification and concept of hydrocephalus shall undergo a major upgrade. Based on such remarkable improvement in the recent practical diagnostic evaluation of fetal hydrocephalus, it is now required to update the guideline for management and treatment of fetal and congenital hydrocephalus, and a nationwide study group; Center of Excellence-Fetal Hydrocephalus Top 10 Japan, was organized in 2008 in Japan. The retrospective analysis of 333 cases of congenital hydrocephalus indicated a fact that 43% of these cases were diagnosed prenatally, and the majority of cases were treated in these top 10 institutes in Japan. Now, congenital hydrocephalus diagnosed immediately after birth is regarded as to be based on embryonic stage; brain disorder in patients with congenital hydrocephalus should be considered in conjunction with neuronal mature process of embryonic stage. The fact is supported by the current trends in hydrocephalus research represented by "Perspective Classification of Congenital Hydrocephalus" and "Multi-categorical Hydrocephalus Classification". The ultimate goal of hydrocephalus treatment remains achieving arrested hydrocephalus by shunt surgeries. In the future, to achieve arrested hydrocephalus, minimum quantity of CSF to be drained should be elucidated. Consideration for accurate operative indication of ETV along with new neuroendoscopic device development and analysis of CSF circulation is expected in the future. The data in this prospective multicenter analysis in this guideline are credited in Oxford Evidence level 2b (Grade II).

Long-term outcomes of endoscopic third ventriculostomy for Blake's pouch cyst in adults.

OBJECTIVE: The optimal treatment method for persistent Blake's pouch cyst (BPC) remains unclear owing to its low prevalence. We aimed to characterize a patient population with adult BPC and to identify the risk factors associated with endoscopic third ventriculostomy (ETV) for BPC. This study reports the largest number of BPC cases in adults and is the first report to reveal the long-term outcomes of ETV in such patients. METHODS: We performed a retrospective analysis of data collected from seven adult patients with BPC between 2005 and 2019. They underwent ETV at the Kurume University Hospital and were followed up for five years or more. We extracted data regarding patient age, sex, clinical symptoms, radiological imaging, intraoperative findings and outcomes. RESULTS: The ages of the patients ranged between 30 and 60 years (45 ±â€¯12 years). The mean postoperative follow-up time was 92.1 ±â€¯13.5 months. The overall success rate was 71.4%. The most frequent symptom was headache (86%), followed by mild cognitive impairment (71%). The average cerebrospinal fluid pressure was slightly elevated (18.4 ±â€¯1.4 cmH2O). A decrease in ventricular size (Evans' index) detected early after ETV was associated with satisfactory clinical outcomes (p = 0.02). The incidence of prepontine scarring was observed in all cases of the ETV failure group. A significant risk factor for ETV was the to-and-fro movements of the third ventricle floor after ETV (p = 0.048). CONCLUSIONS: ETV could be a safe and effective treatment option for adult patients with BPC. It is important that prepontine scarring and the to-and-fro movements of the third ventricle after ETV should be confirmed carefully when performing ETV on adult patients with BPC.

"Motion-specific Headache": A Predictor for Diagnosis and Favorable Prognosis after Surgery in Young Patients with Chiari Malformation Type 1.

As headache is known as one of the most common symptoms in the patients with Chiari malformation type 1 (CM1), it is difficult to find out CM1-related headache among the symptoms because headache itself is commonly seen. Herein, we retrospectively review the cases of six CM1 patients complaining only of headache by which they complained of deterioration in daily life activities. The symptom of headache worsened during anteflexion (n = 2; 33%), retroflexion (n = 1; 17%), jumping (n = 3; 50%), going up the stairs (n = 1; 17%), and running (n = 1; 17%). Mean age at the onset was 15.7 years old (ranging 11-18) and four out of six were female. These inductive factors were clearly different from "Valsalva-like maneuvers," although the mechanism might originate from dynamic tonsil changes. We named these headaches as "motion-specific." These headaches radiated to the posterior side. MRI revealed that the extent of tonsillar ectopia was 11.3 mm, while syringomyelia was observed in three out of six patients (50%). All patients underwent surgical treatment, with the "motion-specific headache" completely disappearing 12.5 days thereafter. Although headaches are common, "motion-specific headache" may be a good candidate symptom to distinguish CM1 patients, especially among teenagers with headaches, and a good predictor for favorable outcomes after surgical treatment.

Endoscopic third ventriculostomy for myelomeningocele-related hydrocephalus after shunt failure: Long-term outcome in a series of 8 patients.

OBJECTIVE: Endoscopic third ventriculostomy (ETV) has now become an accepted mode of hydrocephalus treatment. However, the long-term effects of ETV for myelomeningocele-related hydrocephalus (MMC-rH) after shunt malfunction remains unclear. We aimed to assess the long-term outcome and the factors associated with the success of ETV for MMC-rH after shunt malfunction. METHODS: We performed a retrospective analysis of data collected between 2001 and 2018 from 8 patients with MMC-rH after shunt malfunction, who underwent ETV at the Kurume University Hospital and were followed up for at least 5 years. We extracted data regarding age, sex, clinical symptoms, radiological imaging, intraoperative findings, and outcomes. RESULTS: The overall success rate was 62.5% and their ETV success score is 67.5. The most frequent clinical symptom was intracranial hypertension symptoms (100 %), followed by Chiari type II symptoms (87.5 %). In preoperative MRI scans, we observed aqueduct stenosis in 6 cases, Chiari type II malformations in 7 cases, four patients had a narrow prepontine cistern, five patients had an absent septum pellucidum, and three presented with stenosis of the foramen of Monro. All cases in the failure group had the above 5 symptoms. Based on intraoperative findings, a thick third ventricle floor was found in 5 patients. Two patients had a thin hypothalamic adhesion in the third ventricle floor. They had no major complications. CONCLUSION: ETV for MMC-rH after shunt malfunction is an effective treatment option. However, we recommend that a neurosurgeon with extensive experience in neuroendoscopy perform ETV because MMC patients more often had intraventricular malformations than those with other hydrocephalus diseases.

Micro-anatomical structures of the lumbar intervertebral foramen for full-endoscopic spine surgery: review of the literatures.

Percutaneous endoscopic lumbar discectomy (PELD) is a minimally invasive spinal surgical technique. PELD can be performed via 2 routes, transforaminal (TF) or interlaminar. The TF approach is a well-established modality in the treatment of patients with herniated lumbar discs. This technique makes the most of the space within the intervertebral foramen where, as Kambin claimed, the safe approach to the lesion is possible. Knowledge of the lumbar artery with its branches and various ligaments of anatomies of the intervertebral foramen are needed to perform successful surgeries and to reduce complications.

Neurosurgical versus endovascular treatment of spinal dural arteriovenous fistulas: a multicenter study of 195 patients.

OBJECTIVE: The purpose of the present study was to compare the treatment success rates of primary neurosurgical and endovascular treatments in patients with spinal dural arteriovenous fistulas (dAVFs). METHODS: Data from 199 consecutive patients with thoracic and lumbosacral spinal dAVFs were collected from 18 centers. Angiographic and clinical findings, the rate of initial treatment failure or recurrence by procedures, risk factors for treatment failure, complications, and neurological outcomes were statistically analyzed. RESULTS: Spinal dAVFs were frequently detected in the thoracic region (81%), fed by a single feeder (86%), and shunted into an intradural vein via the dura mater. The fistulous connection between the feeder(s) and intradural vein was located at a single spinal level in 195 patients (98%) and at 2 independent levels in 4 patients (2%). Among the neurosurgical (n = 145), and endovascular (n = 50) treatment groups of single dAVFs (n = 195), the rate of initial treatment failure or recurrence was significantly higher in the index endovascular treatment group (0.68% and 36%). A multivariate analysis identified endovascular treatment as an independent risk factor with significantly higher odds of initial treatment failure or recurrence (OR 69; 95% CI 8.7-546). The rate of complications did not significantly differ between the two treatment groups (4.1% for neurosurgical vs 4.0% for endovascular treatment). With a median follow-up of 26 months, improvements of ≥ 1 point in the modified Rankin Scale (mRS) score and Aminoff-Logue gait and Aminoff-Logue micturition grades were observed in 111 (56%), 121 (61%), and 79 (40%) patients, respectively. Independent risk factors for lack of improvement in the Aminoff-Logue gait grades were multiple treatments due to initial treatment failure or recurrence (OR 3.1) and symptom duration (OR 1.02). CONCLUSIONS: Based on data obtained from the largest and most recently assessed multicenter cohort, the present study shows that primary neurosurgery is superior to endovascular treatment for the complete obliteration of spinal dAVFs by a single procedure.

Microsurgical versus endovascular treatment of spinal epidural arteriovenous fistulas with intradural venous drainage: a multicenter study of 81 patients.

OBJECTIVE: Spinal arteriovenous shunts are rare vascular lesions and are classified into 4 types (types I-IV). Due to rapid advances in neuroimaging, spinal epidural AVFs (edAVFs), which are similar to type I spinal dural AVFs (dAVFs), have recently been increasingly reported. These 2 entities have several important differences that influence the treatment strategy selected. The purposes of the present study were to compare angiographic and clinical differences between edAVFs and dAVFs and to provide treatment strategies for edAVFs based on a multicenter cohort. METHODS: A total of 280 consecutive patients with thoracic and lumbosacral spinal dural arteriovenous fistulas (dAVFs) and edAVFs with intradural venous drainage were collected from 19 centers. After angiographic and clinical comparisons, the treatment failure rate by procedure, risk factors for treatment failure, and neurological outcomes were statistically analyzed in edAVF cases. RESULTS: Final diagnoses after an angiographic review included 199 dAVFs and 81 edAVFs. At individual centers, 29 patients (36%) with edAVFs were misdiagnosed with dAVFs. Spinal edAVFs were commonly fed by multiple feeding arteries (54%) shunted into a single or multiple intradural vein(s) (91% and 9%) through a dilated epidural venous plexus. Preoperative modified Rankin Scale (mRS) and Aminoff-Logue gait and micturition grades were worse in patients with edAVFs than in those with dAVFs. Among the microsurgical (n = 42), endovascular (n = 36), and combined (n = 3) treatment groups of edAVFs, the treatment failure rate was significantly higher in the index endovascular treatment group (7.5%, 31%, and 0%, respectively). Endovascular treatment was found to be associated with significantly higher odds of initial treatment failure (OR 5.72, 95% CI 1.45-22.6). In edAVFs, the independent risk factor for treatment failure after microsurgery was the number of intradural draining veins (OR 17.9, 95% CI 1.56-207), while that for treatment failure after the endovascular treatment was the number of feeders (OR 4.11, 95% CI 1.23-13.8). Postoperatively, mRS score and Aminoff-Logue gait and micturition grades significantly improved in edAVFs with a median follow-up of 31 months. CONCLUSIONS: Spinal epidural AVFs with intradural venous drainage are a distinct entity and may be classified as type V spinal vascular malformations. Based on the largest multicenter cohort, this study showed that primary microsurgery was superior to endovascular treatment for initial treatment success in patients with spinal edAVFs.

Edaravone attenuates cerebral ischemic injury by suppressing aquaporin-4.

Aquaporin-4 (AQP4) plays a role in the generation of post-ischemic edema. Pharmacological modulation of AQP4 function may thus provide a novel therapeutic strategy for the treatment of stroke, tumor-associated edema, epilepsy, traumatic brain injury, and other disorders of the central nervous system (CNS) associated with altered brain water balance. Edaravone, a free radical scavenger, is used for the treatment of acute ischemic stroke (AIS) in Japan. In this study, edaravone significantly reduced the infarct area and improved the neurological deficit scores at 24h after reperfusion in a rat transient focal ischemia model. Furthermore, edaravone markedly reduced AQP4 immunoreactivity and protein levels in the cerebral infarct area. In light of observations that edaravone specifically inhibited AQP4 in a rat transient focal ischemia model, we propose that edaravone might reduce cerebral edema through the inhibition of AQP4 expression following cerebral infarction.