The effects of medroxy progesterone acetate on the pro-inflammatory cytokines, TNF-alpha and IL-1beta in the early phase of the spinal cord injury.

OBJECTIVES: Spinal cord injuries (SCIs) have high morbidity and mortality rates and currently the definitive treatment of complete SCIs are still not possible. We investigated the effects of the medroxy progesterone acetate on the pro-inflammatory cytokines, TNF-alpha and IL-1beta in the early phase of the SCI. METHODS: Forty-eight Wistar albino male rats were divided equally into four groups each consisting of 12 rats. All animals underwent T10-T12 laminectomy. We administered placebo, and 8 mg/kg medroxy progesterone acetate (MPA) intra-peritoneally into control and progesterone group at 30 minutes after the clip-compression trauma in spinal cord. We performed only T10-T12 laminectomy and clip-compression trauma in laminectomy and trauma group, respectively. Half of the rats from each group were killed at 1 hour and the other half were killed at 6 hours after the trauma. Spinal cord segments were then removed and stored at -80 °C in phosphate buffer. TNF-alpha and IL-1beta levels were determined using ELISA kit. RESULTS: We have found that there was an increase only in the TNF-alpha level at 6 hours after the trauma comparing to control group. MPA appeared to lower the TNF-alpha level significantly in the trauma group. DISCUSSION: This experimentally proven anti-inflammatory effect of MPA via acting upon TNF-alpha may offer new therapeutic options in human subjects with SCIs.

Neuroprotective effects of tamoxifen on experimental spinal cord injury in rats.

The aim of this study was to evaluate the effects of tamoxifen on tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) levels and ultrastructural changes in rats with spinal cord injury. Rats were divided into four groups: control group (laminectomy only), trauma group (laminectomy+spinal trauma), tamoxifen group (laminectomy+spinal trauma+tamoxifen), and vehicle group (laminectomy+spinal trauma+vehicle). Spinal cords were extirpated at the T(7)-T(12) level and tissue samples from the spinal cords were gathered for TNF-alpha and IL-1beta measurements at 1 and 6hours. Spinal cords harvested at 6 hours were evaluated for ultrastructural changes. TNF-alpha and IL-1beta levels at 6 hours were significantly lower in the tamoxifen group than in the trauma group. Electron microscopic examination of tissue from the trauma group revealed gross cell deformities with widespread edema of all structures as well as severe edema in the neuropil. At 6 hours after trauma, these ultrastructural changes were less marked in the tamoxifen group. Our findings support a neuroprotective and restorative role for tamoxifen in the context of secondary pathological biochemical events after SCI.

Doxorubicin for prevention of epineurial fibrosis in a rat sciatic nerve model: outcome based on gross postsurgical, histopathological, and ultrastructural findings.

OBJECT: Epineural fibrosis may complicate peripheral nerve surgeries and currently is considered as one of the main factors responsible for failed surgeries. The authors investigated the postoperative antiscarring effects of topically applied doxorubicin (DXR) on rat sciatic nerves. METHODS: The sciatic nerves were dissected from the surrounding tissue and exposed bilaterally in 20 Wistar albino adult male rats. Abrasion trauma was produced on the exposed surface of the biceps femoris muscle in the vicinity of the sciatic nerves and their main branches in all animals. In the DXR Group, cottonoid pads soaked with DXR (0.5 mg/ml) were placed around the nerves for 5 minutes, whereas cotton pads soaked with saline (0.9% NaCl) were applied to nerves of animals in the Control Group for the same duration. Twelve weeks after the procedure, all of the rats were killed and the sciatic nerves were examined. Epineural adhesions were evaluated histopathologically and ultrastructurally. Additionally, quantitative histological parameters, the scar tissue formation index and the scar density, were calculated in histological evaluation. RESULTS: Gross postsurgical evaluation as well as histopathological and electron microscopic examination of involved nerve segments showed significantly less epineurial adhesions in the DXR Group than in the Control Group. Quantitative analysis of the epineurium revealed a statistically significant reduction in the density and amount of epineural scarring in specimens from the DXR Group than in those from the Control Group. CONCLUSIONS: The results of gross postsurgical anatomical evaluation and histopathological and ultrastructural studies suggested that topical application of DXR effectively reduced epineural scar formation on rat sciatic nerves. These promising findings merit further experimental and clinical studies to determine the efficacy and safe applicability of DXR in human subjects.

Effects of memantine and MK-801 on ischemia in an experimental model of acute subdural hematoma.

OBJECTIVE: Cerebral ischemia due to secondary injuries plays an important role in the high mortality rate of acute subdural hematoma (SDH). Although promising results were obtained from experimental works with excitatory amino acid (EAA) antagonists which inhibit the excitotoxic mechanism in the development of cerebral ischemia, these agents could not be used clinically due to their psychomimetic side effects. Memantine, also an EAA antagonist, has been used for a long time in the treatment of different neurodegenerative diseases; however, it was not used in treatment of acute subdural hematoma before. This study has been designed to investigate the development of cerebral ischemia and ischemic edema under experimental acute subdural hematoma and the effect of memantine (Sigma M-9292) and MK-801 (Sigma M-107) in the treatment of ischemia. METHODS: Forty-two adult female Sprague-Dawley rats were divided into two groups: Group A for investigation of ischemia related to SDH and its treatment, and Group B for investigation of cerebral edema. Both groups were further divided into five subgroups, i.e. for sham operations, formation of SDH and treatment with saline, MK-801 and memantine. Treatment of cerebral edema could not be investigated because formation of cerebral edema could not be proven statistically. For evaluation of ischemia, the ratio of ischemic area/the total brain area was calculated as percentages in coronal slices of the rats' brains. RESULTS: In all of the evaluated slices, statistical analysis showed that treatment with MK-801 as well as memantine reduced ischemia caused by SDH. DISCUSSION: Our study showed that memantine, which is already considered as a safe treatment alternative for other central nervous system (CNS) diseases, can be useful in the treatment of acute SDH as well.

Spinal epidural abscess due to Brucella.

BACKGROUND: Brucellar spinal epidural abscess (SEA) is a rarely encountered clinical entity during the course of the systemic Brucella infection. METHODS: We reported 9 patients diagnosed with Brucellar SEA with a mean follow-up of 20 months. Spinal epidural abscess was detected by magnetic resonance imaging in all cases. Brucella diagnosis was established by specific blood tests. Patients were administered antibiotics for a duration of 6 to 12 weeks. RESULTS: Spinal epidural abscess was localized in lumbar region in 6 patients, dorsal in 2 patients, and cervical in 1 patient. Abscess mimicked disk herniation clinically in 3 patients. Although neurologic examination was normal in 6 patients, we detected motor deficit in 3 patients. Symptoms regressed in all patients but 1 after the institution of antibiotic regimens, and all recovered fully without any sequel. Surgical drainage of abscess was performed in 1 patient. CONCLUSIONS: Proper antibiotic regimens in required doses and duration should be the primary treatment in Brucellar SEA. The criteria for terminating antibiotic therapy are clinical recovery and dissolution of abscess images radiologically. Lastly, should any neurologic deterioration be detected during the course of medical treatment, surgical decompression is to be considered.

A case of intra-dural malignant peripheral nerve sheath tumor in thoracic spine associated with neurofibromatosis type 1.

We present a 25-year-old male patient with neurofibromatosis type 1 (NF1). Thoracic intra-dural extra-medullary tumoral mass was excised gross-totally and the patient was referred to oncology unit. Histopathological diagnosis was malignant peripheral nerve sheath tumor (MPNST), a rare sarcoma with a dismal prognosis. Tumor recurred in its previous site with an adjacent apical mass in the left lung 7 weeks following initial surgery and repeat surgery was performed with complete removal of intra-dural tumor. We report the first patient with intra-dural MPNST localized proximal to conus medullaris; in upper thoracic spine. It must always be considered the possibility of a rare but a devastating tumor, MPNST beside schwannomas and neurofibromas in patients with NF1 when an intra-spinal mass is diagnosed.

The effects of memantine on lipid peroxidation following closed-head trauma in rats.

Memantine is an uncompetitive N-methyl-D: -aspartate (NMDA) receptor antagonist. Unlike other NMDA antagonists, it has been used clinically for years for the treatment of Parkinson's disease, spasticity, and dementia without serious side effects. We aimed to investigate the therapeutic efficacy of memantine on a closed head trauma model. A total of 132 adult male Sprague-Dawley rats were randomly divided into four groups: sham-operated, control (closed head trauma), sham-vehicle (closed head trauma + saline), treatment (closed head trauma + memantine, 10 mg/kg, i.p.). A cranial impact was delivered to the skull, just in front of the coronal suture, over the left hemisphere, from the height of 7 cm. Saline or memantine were applied 15 min after trauma. Rats were euthanased 0.5, 1, 2, 6, 24, 48 h after trauma. Brain tissue samples were taken 5 mm away from the left frontal pole and also from the corresponding point of the contralateral hemispheres. Malondialdehyde activity (MDA) was considered to reflect the degree of lipid peroxidation. The MDA levels continued to increase for the first 2 h after the injury, then started to decrease gradually. Memantine treatment significantly reduced lipid peroxidation levels in the treatment group compared with other groups (P<0.01). The findings of the present study indicate that memantine provides beneficial effects after closed head trauma in rats.

The effect of epidural free fat graft on the outcome of lumbar disc surgery.

Numerous materials have been used to prevent epidural scar tissue after lumbar disc surgery. Free fat grafts are common both experimentally and clinically, but there is some doubt about their protection against fibrosis, and some complications have been reported. In this prospective study, the usefulness of free fat grafts during lumbar disc surgery was evaluated. Ninety-nine patients who had undergone operation due to lumbar disc herniation were divided in two groups: those with implantation of free fat grafts (group A) and those without (group B). Outcome was evaluated at a mean of 2.6 years postoperatively according to the following criteria: visual analog scale for back and leg pain, Hannover Questionnaire on activities of daily living, reflex findings, sensory and motor deficits, consumption of analgesics, walking distance, straight leg raising test, and clinical examination. The outcome variables showed no significant differences between the two groups ( P>0.05). This study suggests that the use of free fat grafts during lumbar disc surgery was clinically ineffective.

The effect of low-dose external beam radiation on extraneural scarring after peripheral nerve surgery in rats.

OBJECTIVE: Scar tissue is an inevitable result of peripheral nerve surgery. A variety of substances have been used to prevent epineurial scarring. In this study, the effect of low-dose radiation therapy on epineurial scarring was investigated. METHODS: Seventy-eight male Sprague-Dawley rats were studied. A total of 60 rats were subjected to one of three types of surgical procedure on the sciatic nerve, as follows: Procedure 1, external neurolysis (n = 20); Procedure 2, abrasive injury (n = 20); and Procedure 3, anastomosis (n = 20). On the left sciatic nerves, 700 cGy external beam radiation was administered 24 hours after surgery, and the right sciatic nerves served as a control group (surgery only). Eighteen animals without surgical intervention were used to establish the fibrotic effect of radiotherapy on normal nerves. A neurological examination was performed weekly. Six weeks after surgery, the extent of extraneural scarring was examined by gross microdissection by means of a numerical grading scheme and histological analysis. Cellular density and surface measurements of scar tissue were also evaluated. RESULTS: The dissection around the nerve was easier in rats treated with low-dose radiation compared with the control group. Furthermore, grading scores in both nerve adherence and nerve separability were significantly lower in treated nerves than in the control group (P < or = 0.05). Low-dose radiotherapy decreased the scores of cellular density and surface measurement of scar tissue (P < or = 0.05). In normal nerves, radiotherapy did not produce any fibrotic effects and the density of fibroblasts/fibrocytes was also very low. CONCLUSION: In the case of surgery or local trauma to peripheral nerve, the use of low-dose radiation therapy may be a safe method of limiting postoperative epineurial scar formation.