Imaging Features of Early Diffuse Idiopathic Skeletal Hyperostosis (pre-DISH): Analysis of Progression of Ligament Ossification over 5 Years by Computed Tomography.

Introduction: Some patients who have not been diagnosed with diffuse idiopathic skeletal hyperostosis (DISH) (patients in the preclinical stage of DISH [pre-DISH]) may develop DISH in the future. However, there are currently no clearly defined diagnostic criteria for pre-DISH. This study aims to define pre-DISH by analyzing the change in the ossification extent in each intervertebral space in the thoracic and lumbar spines over time using computed tomography (CT). Methods: Of the patients who underwent CT of the thoracic to pelvic region at least twice from 2009 to 2018, 188 who underwent CT at an interval of 5 years to 5 years and 2 months were enrolled. The prevalence of DISH during the first and second CT scans was investigated. The pre-DISH feature was defined, and the prevalence of pre-DISH on the first CT and the change after 5 years in patients with pre-DISH was investigated. Results: Of the 188 patients, 37 (19.7%) and 48 (25.5%) were diagnosed with DISH on the first and second CT scans, respectively. Pre-DISH was defined as the ossification characterized by the modified Mata score of three contiguous intervertebral spaces with a score of ≥2 points (222; 2 points, ligament ossification of half or more of the intervertebral disc height but incomplete fusion), and 52 patients were diagnosed with pre-DISH. Of the 52 patients with a score of ≥(222), 11 (21.2%) were diagnosed with DISH 5 years later. Conclusions: Patients who have three contiguous intervertebral spaces with a modified Mata score of 2 or 3 points should be considered pre-DISH.

A Scoring System for Anterior Longitudinal Ligament Ossification of the Lumbar Spine in Diffuse Idiopathic Skeletal Hyperostosis: Relationship Between the Extent of Ligament Ossification and the Range of Motion.

STUDY DESIGN: Retrospective observational study. OBJECTIVE: To investigate the relationship between the extent of ligament ossification and the range of motion (ROM) of the lumbar spine and develop a new scoring system. METHODS: Forty-three patients (30 men and 13 women) with lumbar spinal canal stenosis who underwent decompression from January to December 2018. Ligament ossification at L1/2 to L5/S was assessed on plain X-ray (Xp) and computed tomography (CT) using a modified Mata scoring system (0 point: no ossification, 1 point: ossification of less than half of the intervertebral disc height, 2 points: ossification of half or more of the intervertebral disc height, 3 points: complete bridging), and the intra-rater and inter-rater reliability of the scoring was assessed. The relationship of the scores with postoperative lumbar ROM was investigated. RESULT: Intra-rater reliability was high (Cronbach's α was 0.74 for L5/S on Xp but 0.8 or above for other sections), as was inter-rater reliability (Cronbach's α was 0.8 or above for all the segments). ROM significantly decreased as the score increased (scores 1 to 2, and 2 to 3). A significant moderate negative correlation was found between the sum of the scores at L1/2-L5/S and the ROM at L1-S (ρ = - 0.4493, P = 0.025). CONCLUSION: Our scoring system reflects lumbar mobility and is reproducible. It is effective for assessing DISH in fractures and spinal conditions, and monitoring effects on treatment outcomes and changes over time.

Examining the Association Between the Extent of Anterior Longitudinal Ligament Ossification Progression and Comorbidities in Diffuse Idiopathic Skeletal Hyperostosis.

BACKGROUND:  It has been documented that diffuse idiopathic skeletal hyperostosis (DISH) exhibits a higher prevalence among elderly, male, and obese individuals. Additionally, diabetes mellitus and other comorbidities are more frequently observed in this patient population. However, there is a lack of reports exploring the correlation between the extent of ossification and these demographic and clinical characteristics. OBJECTIVE: To examine the correlation between comorbidities and the severity of ossification of the anterior longitudinal ligament in patients with DISH. MATERIALS AND METHODS: The study included 468 patients who visited our hospital in 2018-2022. They were divided into DISH and non-DISH groups based on computed tomography image evaluation according to the Resnick criteria. The patients in the two groups were matched for age and sex. We compared comorbidity-related factors including body mass index (BMI), serum markers for metabolic syndrome and renal function, and hemoglobin A1c (HbA1c) levels between the matched groups. Moreover, we examined the correlation between the number of fused vertebral bodies and comorbidity-related factors, age, and sex within the DISH group. RESULTS: The DISH group included significantly more men and elderly patients than the non-DISH group. Furthermore, the average BMI and HbA1c levels were significantly higher in the matched-DISH group than in the matched-non-DISH group, whereas no differences were observed in other markers. In the DISH group, the number of fused vertebral bodies did not correlate with age, sex, BMI, or HbA1c levels. DISCUSSION: BMI and HbA1c levels were significantly higher in patients with DISH than those without; however, the number of fused vertebral bodies and the possibility of having coexisting obesity or diabetes mellitus showed no correlation with the age or sex of the patient. Therefore, each patient should be carefully assessed for ossification severity regardless of age, sex, and the comorbidities they possess.

Hemodynamic deterioration due to increased anterior and posterior cardiac compression during posterior spinal fusion for scoliosis with pectus excavatum.

Hemodynamics may deteriorate during the perioperative period when performing posterior spinal fusion in patients with pectus excavatum and scoliosis. A 13-year-old teenager diagnosed with Marfan syndrome had thoracic scoliosis and pectus excavatum. Thoracic scoliosis was convex to the right, and a right ventricular inflow tract stenosis was observed due to compression induced by the depressed sternum. The patient underwent T3-L4 posterior spinal fusion surgery for scoliosis. Deterioration of hemodynamics was observed when the patient was placed in the prone position or when the thoracic spine was corrected to the left front. Postoperative computed tomography examination showed that the mediastinal space was narrowed due to the corrected thoracic spine. Special attention should be paid in the following cases: (1) severe pectus excavatum, (2) right ventricular inflow tract compression due to depressed sternum on the left side, (3) correction of the thoracic spine on the left front, (4) long-term surgery, and (5) risk of massive bleeding. In some cases, pectus excavatum surgery should be prioritized.

Can Diffuse Idiopathic Skeletal Hyperostosis Be Diagnosed by Plain Lumbar Spine X-Ray Findings Alone?

STUDY DESIGN: Retrospective case-control study. OBJECTIVES: To determine whether diffuse idiopathic skeletal hyperostosis (DISH) can be diagnosed based on anterior longitudinal ligamental ossification in the lumbar spine using plain lumbar spine X-ray images. METHODS: This study included 100 patients (59 men and 41 women; mean age, 64.8 ± 13.8 years; range, 27-89 years) who underwent computed tomography (CT) of the chest to the pelvis in our hospital and plain lumbar spine radiography within 6 months before and after CT scanning. DISH was diagnosed based on the thoracolumbar spine CT findings using Resnick's diagnostic criteria. The patients were grouped according to DISH diagnosis into the DISH (+) and DISH (-) groups. On the frontal and lateral lumbar spine X-ray images, each spinal level from Th11/12 to L5/S was scored based on the Mata scoring system. The distribution of the Mata scores was compared between the 2 groups. RESULTS: Forty (40%) patients were diagnosed with DISH based on the CT findings. A cutoff value ≥8 provided a sensitivity of 75% and specificity of 100% for diagnosing DISH, thus, indicating the validity of the cutoff value. In the DISH (-) group, no patient had ≥3 consecutive spinal levels with a Mata score ≥2, suggesting that DISH can be diagnosed on the basis of at least 3 consecutive spinal levels with a Mata score ≥2. CONCLUSION: On lumbar spine X-ray images of the T11/12 to L5/S levels, a Mata score ≥2 for at least 3 consecutive levels or a total score ≥8 strongly indicates the presence of DISH.

Serum lactate dehydrogenase levels predict the prognosis of patients with soft tissue sarcoma.

Several studies have reported the prognostic factors for soft tissue sarcoma. Although serum lactate dehydrogenase (LDH) levels are associated with poor prognosis in several types of cancer, their role in soft tissue sarcomas remains unclear. Therefore, the present study evaluated the association between serum LDH levels and the clinical characteristics and prognosis of soft tissue sarcoma. A total of 103 patients diagnosed with primary soft tissue sarcoma between 2003 and 2019 were retrospectively examined, and the association between serum LDH levels at the first visit and clinical characteristics were analysed. In high-grade soft tissue sarcoma, the association between survival and clinical characteristics, including stratified LDH levels, was also analysed. Serum LDH levels were stratified (>253 and ≤253 IU/l) according to the standard values used at our institution. High serum LDH levels were significantly associated with the presence of metastasis and histological grade (P<0.001 and 0.040, respectively). In both the univariate and multivariate analyses, disease-specific survival (DSS) was significantly worse in patients with high-grade soft tissue sarcoma and high serum LDH levels than in patients with normal serum LDH levels (univariate analysis: P=0.025; multivariate analysis: Hazard ratio, 4.60; 95% confidence interval, 1.16-18.2; P=0.030). In conclusion, high serum LDH levels at the first visit predicted the presence of distant metastasis, high histological grade and worse DSS in patients with high-grade soft tissue sarcoma. Therefore, in patients with high serum LDH levels at the first visit, these risks should be considered during pretreatment examinations and post-treatment follow-up.

Thoracic spondylotic myelopathy presumably caused by diffuse idiopathic skeletal hyperostosis in a patient who underwent decompression and percutaneous pedicle screw fixation.

A 74-year-old man developed bilateral lower limb spastic paresis. He was diagnosed with thoracic spondylotic myelopathy presumably caused by mechanical stress that was generated in the intervertebral space (T1-T2) between a vertebral bone bridge (C5-T1) due to diffuse idiopathic skeletal hyperostosis after anterior fixation of the lower cervical spine and a vertebral bone bridge (T2-T7) due to diffuse idiopathic skeletal hyperostosis in the upper thoracic spine. Treatment included posterior decompression (T1-T2 laminectomy) and percutaneous pedicle screw fixation at the C7-T4 level. Six months after surgery, the patient could walk with a cane, and the vertebral bodies T1-T2 were bridged without bone grafting. For thoracic spondylotic myelopathy associated with diffuse idiopathic skeletal hyperostosis, decompression and percutaneous pedicle screw fixation are effective therapies.

Diffuse idiopathic skeletal hyperostosis: A potential factor in the induction of thoracic spondylotic myelopathy.

BACKGROUND: Thoracic spondylotic myelopathy (TSM) commonly occurs at the thoracolumbar junction, and mechanical stress is thought to be involved. In DISH, the anterior longitudinal ligament becomes ossified. Although DISH is suspected to be involved in TSM pathology, reports are limited. Aim of this study is to investigate the association between (TSM) and diffuse idiopathic skeletal hyperostosis (DISH). METHODS: Fifty-one patients with thoracic myelopathy underwent surgery between April 2008 and April 2017. Of these, 28 patients with TSM were included and examined. DISH was confirmed using computed tomography (CT). Subjects were divided into DISH and non-DISH sub-groups according to CT findings, and the DISH coexistence rate was calculated. Groups were analyzed for sex, age, postoperative Japanese Orthopedic Association (JOA) score, and reoperation status. In the DISH group, the positional relationship between the affected vertebral level of TSM and consecutive vertebral bone bridges was analyzed. Patients without spinal disease matched for sex and age were enrolled as controls (N = 56). The DISH coexistence rate was compared and analyzed between groups. RESULTS: Mean age at surgery was 67.8 years (43-82 years; 22 men, 6 women). DISH was detected in 17 of 28 patients (60.7%; 15 men, 2 women). No significant difference in the improvement rate of JOA score was observed between groups. TSM occurred at: lower border of a consecutive vertebral bone bridge, N = 4; upper border, N = 3; between consecutive vertebral bone bridges, N = 5; one vertebral body away from a consecutive vertebral bone bridge, N = 5. No patient had TSM occurring within a consecutive vertebral bone bridge. The DISH coexistence rate in patients with TSM (60.7%) was significantly higher than that in controls (20/56, 35.7%) (p = 0.03). CONCLUSION: Mechanical stress caused by consecutive vertebral bone bridges due to DISH may be involved in TSM pathogenesis. Therefore, in DISH patients, attention needs to be paid to TSM onset.

Progression of Ossification of the Anterior Longitudinal Ligament Associated With Diffuse Idiopathic Skeletal Hyperostosis by Age: A Study of Computed Tomography Findings Over 5 Years.

STUDY DESIGN: Observational study. OBJECTIVE: To investigate whether the progression of anterior longitudinal ligament ossification varies by age among patients with diffuse idiopathic skeletal hyperostosis (DISH). METHODS: Of the patients who underwent computed tomography (CT) of the thoracic to pelvic region at least twice from 2009 to 2018, 191 who underwent CT at an interval of 5 years and 0 months to 5 years and 2 months were enrolled (87 men and 104 women). Sex, age at the time of the first CT scan, the presence/absence of DISH, level of complete vertebral body fusion associated with DISH, and extent of ligament ossification using the modified Mata scoring system were investigated. RESULTS: DISHs were detected in 53 (27.7%) of 191 patients. The score of ligament ossification increased over time in 35 (66%) of 53 patients; 93 intervertebral spaces were affected. The percentage of completely fused intervertebral spaces increased by 6.7% from 31.3% to 38.0% over time. The increase in score for all intervertebral spaces in individual patients was significantly greater in the ≤70 years old group (2.7 ± 2.8 points, n = 28) than in the ≥71 years old group (1.2 ± 1.4 points; n = 25; P = .028). The mean age of patients with a recorded score that increased by ≥1 point was 67.4 years and that of patients without any change in the score was 73.3 years (P = .036). Thus, patients with recorded changes in the score were younger. CONCLUSION: During the approximately 5-year period, ossification progressed more in younger patients than in older patients.

Association Between Vertebral Fracture and Diffuse Idiopathic Skeletal Hyperostosis.

STUDY DESIGN: Retrospective case-control study. OBJECTIVE: To investigate the prevalence and characteristics of diffuse idiopathic skeletal hyperostosis (DISH) in vertebral fracture patients admitted to our hospital. SUMMARY OF BACKGROUND DATA: Although vertebral fracture is generally treated conservatively with rest and use of a corset, surgery with rigid internal fixation is recommended for vertebral fractures in patients with DISH. Thus, treatment strategies for vertebral fracture differ according to the presence or absence of DISH. However, only a few studies have investigated the prevalence of DISH in vertebral fracture patients. METHODS: A total of 159 patients (49 men and 110 women, with a mean age of 82.9 years) who were diagnosed with fresh vertebral fracture and required admission to HITO Hospital. The diagnosis of fresh vertebral fracture was made using x-ray imaging, computed tomography, and magnetic resonance imaging, and the presence or absence of DISH was assessed. In addition, age, sex, bone mineral density ( % young adult mean), blood test results, treatment, and length of hospital stay were compared between patients with and without DISH. RESULTS: The proportion of patients with DISH among the patients with vertebral fracture was 33.9% (54 of 159 patients). The proportions in men and women were 38.8% and 31.8%, respectively, with no significant difference between sexes (P = 0.39). The patients in the DISH group were older than those in the non-DISH group (83.6 vs. 79.4 years, P = 0.009), and the DISH group had higher glycated hemoglobin A1c (P = 0.005), higher bone mineral density (P = 0.042), and longer length of hospital stay (P = 0.0001) compared with those in the non-DISH group. CONCLUSION: The proportion of patients with DISH among the vertebral fracture patients was 33.9%. Given that patients with DISH may require different treatment approaches, careful observation is needed. LEVEL OF EVIDENCE: 3.

Risk Factors for Delirium after Spine Surgery: An Age-Matched Analysis.

STUDY DESIGN: A retrospective cohort study. PURPOSE: To investigate the risk factors for postoperative delirium after spine surgery, excluding older age, which has already been established as a strong risk factor. OVERVIEW OF LITERATURE: More than 30 risk factors have been reported for delirium after spine surgery, making it challenging to identify which factors should be prioritized. We hypothesized that risk factors could not be prioritized to date because the factor of older age is very strong and influenced other factors. To eliminate the influence of older age, we performed an age-matched group comparison analysis for the investigation of other risk factors. METHODS: This study involved 532 patients who underwent spine surgery. Two patients of the same age without delirium (delirium negative group) were matched to each patient with delirium (delirium positive group). Differences in suspected risk factors for postoperative delirium between the two groups identified from previous reports were analyzed using univariate analysis. Multivariate analysis was performed for factors that showed a significant difference between the two groups in the univariate analysis. RESULTS: Fifty-nine (11.1%) of 532 patients developed postoperative delirium after spine surgery. Large amounts of intraoperative bleeding, low preoperative concentration of serum Na, high postoperative (day after surgery) serum level of C-reactive protein, low hematocrit level, low concentration of albumin, and high body temperature were detected as significant risk factors in the univariate analysis. Large amounts of intraoperative bleeding remained a risk factor for postoperative delirium in the multivariate analysis. CONCLUSIONS: We should pay attention to and take precautions against the occurrence of postoperative delirium after spine surgery in patients of older age or those who experience severe intraoperative bleeding.

Altered Gene Expression of RNF34 and PACAP Possibly Involved in Mechanism of Exercise-Induced Analgesia for Neuropathic Pain in Rats.

Despite the availability of several modalities of treatment, including surgery, pharmacological agents, and nerve blocks, neuropathic pain is often unresponsive and sometimes progresses to intractable chronic pain. Although exercise therapy is a candidate for treatment of neuropathic pain, the mechanism underlying its efficacy has not been elucidated. To clarify the molecular mechanism for pain relief induced by exercise, we measured Rnf34 and Pacap mRNA levels in the spinal cord dorsal horn of SNL rats, a model of neuropathic pain. SNL model rats exhibited stable mechanical hyperalgesia for at least 6 weeks. When the rats were forced to exercise on a treadmill, mechanical and thermal hyperalgesia were significantly ameliorated compared with the non-exercise group. Accordingly, gene expression level of Rnf34 and Pacap were also significantly altered in the time course analysis after surgery. These results suggest that exercise therapy possibly involves pain relief in SNL rats by suppressing Rnf34 and Pacap expression in the spinal cord.

Spinal fusion in a patient with Fukuyama congenital muscular dystrophy.

Many studies have evaluated surgical treatments for spinal deformities in patients with neuromuscular disease. However, few reports have described patients with Fukuyama congenital muscular dystrophy (FCMD). A 13-year-old boy with FCMD was unable to sit for long periods or sleep in the supine position because of progressive scoliosis. His Cobb angle worsened from 27° to 41° in 5months. He underwent standard posterior spinal fusion and pedicle-screw-alone fixation from T5 to S1. Postoperatively, his Cobb angle improved from 41° to 25° without exacerbation for 2years. After the surgery, he was able to sit for longer periods without pain, and he and his family were satisfied with the efficacy of the spinal fusion. Some patients with mild FCMD can sit at the age of puberty, but progression to scoliosis is possible. Therefore, spinal fusion for progressive scoliosis in patients with FCMD should be considered.

Eight years of follow-up after laminectomy of calcium pyrophosphate crystal deposition in the cervical yellow ligament of patient with Coffin-Lowry syndrome: A case report.

BACKGROUND: We report 8 years of follow-up after decompression to treat cervical myelopathy in a patient with Coffin-Lowry syndrome (CLS). CLS is a rare X-linked semidominant syndrome associated with growth and psychomotor retardation, general hypotonia, and skeletal abnormalities. In this patient, the spinal cord was compressed by calcium pyrophosphate crystal deposition in the cervical yellow ligament (YL). To date, only 1 report has described clinical features after surgery for calcified cervical YL in CLS. METHODS: A 15-year-old male with tetraplegia secondary to compression of the cervical spinal cord induced by a hypoplastic posterior arch of C1 and calcification of the YL from C2 to C7 was treated surgically with laminectomy from C1 to C7. The patient's history, clinical examination, imaging findings, and treatment are reported. The patient was incapable of speech because of mental retardation, so he could not describe his symptoms. Gait disturbance worsened over the 2 months before admission to our hospital. At admission, the patient could not move his extremities, and tendon reflexes of the upper and lower extremities were significantly increased. Computed tomography of the cervical spine showed YL calcification from C2 to C7. Magnetic resonance imaging showed consecutive compression of the cervical spinal cord. We diagnosed quadriplegia secondary to cervical cord damage and performed emergency surgery. RESULTS: During C1-C7 laminectomy, YL calcification in C2-C7 was observed. The calcification was confirmed as calcium pyrophosphate by crystal analysis. Quadriplegia gradually resolved, and almost disappeared by 2 weeks after the operation. Cervical hyperlordosis was observed in radiographs starting from 1 month after the operation, but it has not progressed and is not associated with any symptoms. CONCLUSIONS: The efficacy of decompression continued, and no postoperative complications have occurred during at least 8 years of follow-up.

Evaluation of Injured Axons Using Two-Photon Excited Fluorescence Microscopy after Spinal Cord Contusion Injury in YFP-H Line Mice.

Elucidation of the process of degeneration of injured axons is important for the development of therapeutic modules for the treatment of spinal cord injuries. The aim of this study was to establish a method for time-lapse observation of injured axons in living animals after spinal cord contusion injury. YFP (yellow fluorescent protein)-H transgenic mice, which we used in this study, express fluorescence in their nerve fibers. Contusion damage to the spinal cord at the 11th vertebra was performed by IH (Infinite Horizon) impactor, which applied a pressure of 50 kdyn. The damaged spinal cords were re-exposed during the observation period under anesthesia, and then observed by two-photon excited fluorescence microscopy, which can observe deep regions of tissues including spinal cord axons. No significant morphological change of injured axons was observed immediately after injury. Three days after injury, the number of axons decreased, and residual axons were fragmented. Seven days after injury, only fragments were present in the damaged tissue. No hind-limb movement was observed during the observation period after injury. Despite the immediate paresis of hind-limbs following the contusion injury, the morphological degeneration of injured axons was delayed. This method may help clarification of pathophysiology of axon degeneration and development of therapeutic modules for the treatment of spinal cord injury.

Different analgesic effects of adenosine between postoperative and neuropathic pain.

BACKGROUND: Adenosine is an endogenous neuromodulator in both the peripheral and central nervous systems. Adenosine inhibits pain signals by hyperpolarizing neuronal membrane. METHODS: To clarify the effects of adenosine on pain signals, we tested intrathecal adenosine injection in two neuropathic pains (spinal cord compression and chronic constriction of sciatic nerve) and postoperative pain (plantar incision). RESULTS: In all three kinds of pain models, significant shortening of withdrawal latencies to thermal stimulation were detected from 24 h to 1 week after the surgery. Significant improvements of pain sensation were observed in all three models after intrathecal injection of Cl-adenosine 24 h after surgery. At 72 h after surgery, intrathecal Cl-adenosine injection inhibited hyperalgesia in the two neuropathic pain models but not in the postoperative pain model. Adenosine A1R messenger RNA (mRNA) expression significantly decreased in the plantar incision model. Adenosine A1R protein levels also decreased compared with the other two models and normal control. CONCLUSIONS: These results suggest that adenosine effectively inhibits pain signals in neuropathic pain but is less effective in postoperative pain because of the decrease in adenosine A1 receptors.

Cervical myelopathy caused by atlantoaxial instability in a patient with an os odontoideum and total aplasia of the posterior arch of the atlas: a case report.

INTRODUCTION: Congenital hypoplasia of the atlas has rarely been reported. Myelopathy caused by the complete absence of the posterior arch of the atlas has not been reported. This case report describes the diagnosis and successful treatment of a myelopathy due to the complete absence of the posterior arch of the atlas. CASE PRESENTATION: A 59-year-old Japanese man experienced pain in his nuchal region with progressive spasticity, numbness and hypesthesia in his upper and lower limbs. Deep tendon reflexes in his upper and lower limbs were increased. The complete absence of the posterior arch of the atlas and atlantoaxial instability were found in a roentgenogram. Magnetic resonance imaging detected high signal intensity on T2-weighted images in his spinal cord at the level of cervical vertebrae 1 to 2. Our patient underwent posterior occipito-C4 fixation with pedicle screws. After the operation, the pain in his nuchal region disappeared and his symptoms of myelopathy improved. Only slight numbness of his upper limbs remained. CONCLUSIONS: This is the first report of myelopathy due to the complete absence of the posterior arch of the atlas.

p38 mitogen-activated protein kinase inhibitor reduces neurocan production in cultured spinal cord astrocytes.

Chondroitin sulfate proteoglycans are formed in scar tissue after a spinal cord injury and inhibit axon regrowth. The production of neurocan, one of these chondroitin sulfate proteoglycans, in cultured spinal cord astrocytes increased after the addition of epidermal growth factor (EGF) in a dose-dependent manner (2-200 ng/ml). In astrocytes stimulated by 20 ng/ml of EGF, neurocan production was inhibited after the addition of the p38 mitogen-activated protein kinase (MAPK) inhibitor (SB203580: 3-10 µM) in a dose-dependent manner. These results suggest that the activation of p38 MAPK is one of the mechanisms of neurocan production in EGF-stimulated astrocytes. The p38 MAPK inhibitor may reduce neurocan production and accelerate axonal regrowth after a spinal cord injury.

A novel thermoelectric cooling device using Peltier modules for inducing local hypothermia of the spinal cord: the effect of local electrically controlled cooling for the treatment of spinal cord injuries in conscious rats.

We developed a novel thermoelectric cooling device using Peltier modules for the treatment of spinal cord injury in rats. The extracorporeal electrically cooling component was attached to the aluminum arched plate which was placed on the surface of the spinal cord after the contusion injury in the 11th thoracic spinal cord. During the hypothermic treatment, rats were awake and could move in the cage. Hind limb motor function, evaluated using a BBB scale, in the hypothermic animals (33°C for 48 h) was significantly higher than that in the normothermic animals from 2 weeks to 8 weeks after the injury.

Pharmacological shift of the ambiguous nitric oxide action from neurotoxicity to cyclic GMP-mediated protection.

OBJECTIVES: The effect of intracellular cyclic guanosine monophosphate (GMP) increase on neuronal damage was tested using a newly developed nitric oxide-related injury model of cultured spinal cord neurons. METHODS: Neuronal damage after 24-hour-exposure to sodium nitroprusside (SNP), a nitric oxide (NO) donor, was evaluated by measuring the activity of released lactate dehydrogenase from injured neurons. RESULTS: Oxygen radical scavengers had a protective effect, indicating that the neuronal damage, elicited by 10 µM SNP, was largely due to peroxynitrite formation. Alternatively, a strong inhibition of the NO-induced damage could also be achieved by an intracellular cyclic GMP increase resulting from the addition of 100 µM 8-bromo-cyclic GMP. Propentofylline (PPF, 1-100 µM), a xanthine derivative and rather selective phosphodiesterase (PDE) inhibitor, enhanced intracellular cyclic GMP elevation induced by SNP exposure. The neuronal damage induced by 10 µM SNP exposure for 24 hours was almost completely blocked in the presence of 1 µM PPF. DISCUSSION: These results suggest that NO has an ambiguous action, i.e. toxic by favoring the formation of, but protective by intracellular cyclic GMP elevation which can be reinforced by PDE inhibition. Therefore, PDE inhibitors, such as PPF, may be useful therapeutic drugs to limit oxidative neuronal damage in the central nervous system.