Erkan Kaptanoglu

Effect of magnesium sulphate in experimental spinal cord injury: evaluation with ultrastructural findings and early clinical results.

Excitotoxic mechanisms have been implicated in the pathophysiology of spinal cord injury (SCI). The authors have studied the protection against secondary damage to rat spinal cord with magnesium sulphate, a well-known N-methyl-D-aspartate antagonist. Rats were randomly allocated into 5 groups. Group 1 rats were controls and normal spinal cord samples were obtained after clinical examination. 50 g-cm contusion injury was introduced to Group 2. Group 3 was vehicle, 1 cc of physiologic saline was injected post-trauma. Group 4 and 5 were treatment groups and 100 mg/kg and 600 mg/kg of Magnesium sulphate was given immediately after trauma, intraperitoneally. Animals were evaluated with inclined plane, Tarlov motor scale and Basso-Beattie-Bresnahan scale 24h after SCI. Spinal cord samples for ultrastructural evaluations were obtained following clinical examinations. Magnesium treatment improved neurological outcome. Electron microscopic results showed obvious neuroprotection in the treatment groups. Application of 600 mg/kg of magnesium revealed better ultrastructural findings and clinical results than 100 mg/kg. These findings demonstrated that magnesium sulphate possesses neuroprotection on spinal cord ultrastructure and on functional scores after acute contusion injury to the rat spinal cord.

Ultrastructural evaluation of pulsed radiofrequency and conventional radiofrequency lesions in rat sciatic nerve

BACKGROUND PRF treatment has recently been described as minimally neurodestructive alternative to radiofrequency heat lesions. Patients with some pain syndromes in whom the pain could not be controlled by alternative techniques may be treated using PRF. In the present study, our main goal was to evaluate and compare the ultrastructure of peripheral nerve tissue that was heated by PRF, CRF with 42 degrees C, and CRF with 70 degrees C. METHODS Forty-five male rats were divided into 5 groups. In PRF group and CRF with 42 degrees C group, the sciatic nerve was heated at a temperature of 42 degrees C for 120 seconds. As a positive control, some rat sciatic nerves were treated with CRF lesions at 70 degrees C. The rats were kept alive for 21 days and then killed. Tissue was evaluated with transmission electron microscope, and grading was done to the groups. RESULTS The unmyelinated nerve fibers were ultrastructurally normal in all groups. The results of myelinated axons indicated that PRF group had better grades, and CRF with 70 degrees C group had the worst grade. Especially, comparison of the group of PRF and CRF with 42 degrees C revealed significant difference. In PRF group, none of the myelinated axons showed severe degeneration findings, and most of the damaged myelinated axons showed only separation in myelin configuration. CONCLUSIONS PRF treatment may cause separation in myelinated axons. However, it seems that all changes were reversible. The present study supports the hypothesis that pulsed RF treatment does not rely on thermal injury of neurologic tissue to achieve its effect.

Prognostic value of serum neuron-specific enolase levels after head injury

Neuron-specific enolase (NSE) is a dimeric cytoplasmic enzyme detected in high levels in neurons and acts in the glycolytic pathway. It is known that there is a quantitative relationship between the concentration of serum NSE and the degree of cell damage in the central nervous system. We examined serum levels of NSE by enzyme immunoassay in 89 patients with head injury and aimed to evaluate its relationship with neurological status and prognosis of the patients.

Use of pimecrolimus to prevent epidural fibrosis in a postlaminectomy rat model

OBJECT Epidural fibrosis is the scar tissue formed over the dura mater after a laminectomy. Extensive epidural fibrosis may be an important underlying cause of failed back syndrome. Pimecrolimus, an ascomycin derivative, is one of the new classes of immunomodulating macrolactams and was specifically developed for the treatment of inflammatory diseases. This study examined the preventive effects of the local application of pimecrolimus in minimizing spinal epidural fibrosis in a rat laminectomy model. METHODS Thirty Wistar rats were divided into 3 equal groups: control, mitomycin C (MMC), and pimecrolimus groups. Each rat underwent a laminectomy at the L-3 lumbar level. In the experimental groups, a cotton pad soaked with MMC (0.5 mg/ml) or 5 mg pimecrolimus was placed on the exposed dura mater. No treatment was performed in the control group rats. Thirty days after surgery, the rats were killed and the dura mater thickness, epidural fibrosis, and arachnoidal involvement were quantified. RESULTS The mean dura thickness was measured at 9.28 +/- 3.39 microm in the MMC group and at 8.69 +/- 2.32 microm in the pimecrolimus group, compared with 14.70 +/- 4.14 microm in the control group. In addition, the epidural fibrosis and arachnoidal involvement were reduced significantly in the treatment groups compared with the control group. CONCLUSIONS In this animal model, it was shown that locally applied pimecrolimus effectively reduces epidural fibrosis and dural adherence in rats that underwent lumbar laminectomy. Mitomycin C was equally effective as pimecrolimus in reducing epidural fibrosis and dural adherence in this study.

Antioxidant actions and early ultrastructural findings of thiopental and propofol in experimental spinal cord injury.

Thiopental and propofol are effective antioxidant agents. The current study was undertaken to examine the neuroprotective effects of a single intraperitoneal dose of thiopental and propofol. Effects of the drugs were evaluated by lipid peroxidation and ultrastructural findings. Fifty male Wistar rats were divided into five groups. Group 1 was the control group. Rats underwent laminectomy only, and nontraumatized spinal cord samples were obtained 1 hour after surgical intervention. All other rats sustained a 50-g/cm contusion injury by the weight drop technique. Group 2 rats underwent spinal cord injury alone, group 3 rats received 1 mL intralipid solution intraperitoneally immediately after trauma as the vehicle group, group 4 rats received a 15-mg/kg single dose of thiopental, and group 5 rats received a 40-mg/kg single dose of propofol intraperitoneally following the trauma. Samples from groups 2, 3, 4, and 5 were obtained 1 hour after injury. Lipid peroxidation was determined by measuring the concentration of malondialdehyde in the spinal cord tissue. The ultrastructure of the spinal cord was determined by electron microscopy. The contusion injury was associated with a rise in lipid peroxidation. Compared with the trauma group there was significant attenuation in lipid peroxidation of groups 4 and 5. Ultrastructural findings showed that the rats of group 4 sustained minor damage after spinal cord injury, but there was more evident damage in group 5 rats. These results indicate that thiopental decreases lipid peroxidation and improves ultrastructure, whereas propofol decreases lipid peroxidation without improving ultrastructure 1 hour after spinal cord injury in rats.

Increased xanthine oxidase activity after traumatic brain injury in rats.

Oxidative stress may contribute to many of the pathophysiologic changes that occur after traumatic brain injury (TBI). There are a number of potential sources and mechanisms for oxygen free radical (OFR) production and lipid peroxidation after TBI. In this study, we investigate the time-dependent changes in xanthine oxidase (XO) activity and lipid peroxidation using a focal TBI animal model. We demonstrate that there is an immediate increase in lipid peroxidation by-products and in XO enzyme activity after TBI.

An attempt to treat patients who have injured spinal cords with intralesional implantation of concentrated autologous bone marrow cells

BACKGROUND AIMS Spinal cord injury is common among young subjects involved in motor vehicle accidents. Mechanisms and attempts to reverse post-traumatic pathophysiologic consequences are still being investigated. Unfortunately no effective and well-established treatment modality has been developed so far. The regeneration capability of the human nervous system following an injury is highly limited. METHODS The study involved four patients (two male, two female) who had suffered spinal cord injury as a result of various types of trauma. On neurologic examination, all the patients were determined to be in American Spinal Injury Association (ASIA) grade A. All patients were treated with decompression, stabilization and fusion for vertebral trauma anteriorly, as well as intralesional implantation of cellular bone marrow concentrates using a posterior approach 1 month after the first operation. The patients were then treated and followed-up in the physical rehabilitation clinic. RESULTS At the end of the post-operative 1-year follow-up, two of the patients were classified as ASIA C while one was classified as ASIA B. One patient showed no neurologic change; none of the patients suffered from any complications or adverse effects as a result of intralesional application of bone marrow cells. CONCLUSIONS The results of this experimental study show the potential contribution of intralesional implantation of bone marrow to neuronal regeneration in the injured spinal cord, with neuronal changes. In light of the results of this experimental study, the potential for regenerative treatment in injuries of the human spinal cord is no longer a speculation but an observation.

Metoprolol treatment decreases tissue myeloperoxidase activity after spinal cord injury in rats.

Neutrophil infiltration has been reported to play an important role in spinal cord injury (SCI). In addition to their cardioprotective effects, beta-blockers have been found to have neuroprotective effects on the central nervous system, but their effect on SCI has not yet been studied. In the current study, we investigated the effect of metoprolol on myeloperoxidase (MPO) activity, a marker of neutrophil activation, in the spinal cord after experimental SCI in rats. Rats were divided into six groups: controls received only laminectomy and spinal cord samples were taken immediately; the sham operated group received laminectomy, and spinal cord samples were taken 4h after laminectomy; the trauma only group underwent a 50g/cm contusion injury but received no medication; and three other groups underwent trauma as for the trauma group, and received 30mg/kg methylprednisolone, 1mg/kg metoprolol, or 1mL saline, respectively. All the medications were given intraperitoneally as single doses, immediately after trauma. Spinal cord samples were taken 4h after trauma and studied for MPO activity. The results showed that tissue MPO activity increased after injury. Both metoprolol and methylprednisolone treatments decreased MPO activity, indicating a reduction in neutrophil infiltration in damaged tissue. The effect of metoprolol on MPO activity was found to be similar to methylprednisolone. In view of these data, we conclude that metoprolol may be effective in protecting rat spinal cord from secondary injury.

Effect of granulocyte-colony stimulating factor on spinal cord tissue after experimental contusion injury

The purpose of this study was to investigate the early effects of granulocyte-colony stimulating factor (G-CSF) on myeloperoxidase (MPO) activity, lipid peroxidation (LPO) and ultrastructural findings in rats after spinal cord injury (SCI). We also compared the effects of G-CSF and methylprednisolone sodium succinate (MPSS). Wistar rats were divided into four groups: control, SCI alone (50 g/cm weight drop trauma), SCI+MPSS (30 mg/kg), and SCI+G-CSF (50 μg/kg). Administration of G-CSF and MPSS significantly decreased LPO (p < 0.05) and MPO activity (p < 0.05) in the first 24 hours. MPSS was more effective than G-CSF in reducing LPO (p < 0.05) and in minimizing ultrastructure changes. The results of this study indicate that G-CSF exerts a beneficial effect by decreasing MPO activity and LPO and may reduce tissue damage in the first 24 hours after SCI. Our findings do not exclude the possibility that G-CSF has a protective effect on spinal cord ultrastructure after the first 24 hours following SCI.

Blockade of sodium channels by phenytoin protects ultrastructure and attenuates lipid peroxidation in experimental spinal cord injury

SummarySpinal cord injury (SCI) involves a series of pathological events. Abnormal sodium influx has been implicated as one of the key events in the pathophysiology of the SCI. Pharmacological blockade of sodium channels can reduce secondary injury and increase recovery from trauma. The aim of the present study was to show the neuroprotective effect of phenytoin, a sodium channel blocker, after experimental SCI.Control and laminectomy-only groups were not injured. 50 g-cm weight drop injury was produced in the trauma group. In the treatment groups, methylprednisolone (30 mg/kg) and phenytoin (1 mg/kg, 10 mg/kg, or 30 mg/kg) were given intraperitoneally immediately after injury. Malondialdehyde (MDA) levels in the spinal cord samples were examined for lipid peroxidation. Spinal cord ultrastructure was evaluated and grading system was used for quantitative evaluation.Trauma increased tissue MDA levels. Treatment with methylprednisolone and phenytoin decreased MDA levels compared to trauma in all doses. Significant ultrastructural neuroprotection was observed with 30 mg/kg of phenytoin treatment according to general neural score. This ultrastructural neuroprotection of phenytoin was not different from methylprednisolone. Phenytoin appears to protect spinal cord against injury by decreasing lipid peroxidation and lessening neuronal damage associated with SCI in rats.