Omer Besalti

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.

Lamotrigine attenuates cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits.

BACKGROUND Increasing evidence implicates voltage-dependent sodium and potassium channels, in addition to calcium channels of various types, in the pathophysiological development of cerebral vasospasm. This study investigated the ability of LTG, an antiepileptic drug with multi-ion channel inhibition properties, to prevent cerebral vasospasm and subsequent neural ischemia in a rabbit model of SAH. METHODS Thirty-five New Zealand white rabbits were assigned to 1 of 3 groups: (1) control (no SAH, saline injection); (2) SAH alone; (3) SAH + LTG, 20 mg/kg daily. Animals were killed 72 hours after SAH, then basilar artery lumen areas and arterial wall thickness were measured in all groups. The histological sections of the CA1 and CA3 regions and dentate gyri of the hippocampi were evaluated semiquantitatively for neural tissue degeneration. RESULTS In the SAH group, the mean luminal cross-sectional area of the basilar artery was reduced by 62% after SAH as compared with the non-SAH controls (P < .0001). After SAH, the vasospastic response was attenuated by 36% in animals treated with 20 mg/kg of LTG compared with the SAH group (P < .005). The mean luminal cross-sectional areas of the basilar artery were 279000 +/- 27000 microm(2) in the control group, 173000 +/- 17600 microm(2) in the SAH group, and 236000 +/- 10000 microm(2) in the SAH + LTG group. The differences between the SAH group and the LTG-treated group were statistically significant (P < .0001). Histological examination was done in 12 control, 12 SAH, and 9 SAH + LTG-treated animals. The mean degeneration score for the control group and SAH + LTG group was statistically significant (P = .012). The difference between the SAH group and SAH+ LTG group was also statistically significant (P = .006). CONCLUSIONS These findings demonstrate that oral administration of LTG has marked neuroprotective effect and significantly attenuates cerebral vasospasm after SAH, thus providing additional support for the role of non-L-type calcium channels and voltage-dependent sodium channels in vasospasm.

Leflunomide prevents vasospasm secondary to subarachnoid haemorrhage

SummaryBackground. Though cerebral vasospasm is one of the most serious complications of subarachnoid haemorrhage (SAH), its complex pathogenesis is poorly understood and available clinical treatment options are unsatisfactory. This study was designed to examine the efficacy of leflunomide, an immunomodulatory agent with inhibitory properties, on vascular smooth muscle cell proliferation and inflammation in a rabbit cerebral vasospasm model. Methods. Twenty-two adult New-Zealand rabbits were assigned to 4 groups: control, SAH, SAH plus vehicle, SAH plus leflunomide. Subarachnoid haemorrhage was induced by administration of 1 ml of fresh unheparinised autologous arterial blood into the cisterna magna. Oral leflunomide (2 mg/kg) or vehicle treatment was started 12 h after the induction of subarachnoid haemorrhage and administered once a day. Three days later, the animals were sacrificed and the basilar artery was examined histologically for the lumen area and the thickness of the vessel wall. Inflammatory reaction was also examined by counting white blood cells within the vessel wall by means of light microscopic examination using haematoxylin and eosin staining. Findings. Severe and moderate vasospasms were detected in the basilar artery of the SAH and SAH plus vehicle treated groups, respectively. Leflunomide effectively reduced the vasospasm of the basilar artery. Compared to the vehicle treated group, leflunomide significantly reduced the lumen area (p < 0.01) and hyperplasia of the vessel wall (p < 0.01). Although inflammatory response within the vessel wall was reduced in the leflunomide treated group, no statistical significance was found between groups (p = 0.07). Conclusion. This study demonstrates for the first time that leflunomide treatment attenuates cerebral vasospasm in a rabbit SAH model while inflammatory reaction in the vessel wall is not affected. Although further studies are needed to reveal its molecular mechanisms in relieving vasospasm, leflunomide may provide a therapeutic potential for human cerebral vasospasm induced by SAH.

Effect of curcumin on lipid peroxidation, early ultrastructural findings and neurological recovery after experimental spinal cord contusion injury in rats.

AIM After acute spinal cord injury (SCI), a large number of axons are lost by a cascade of pathophysiological events known as a secondary injury. The main aim of the current study was to investigate the potential neuroprotective effects of curcumin on lipid peroxidation (LPO), neurological function, and ultrastructural findings after SCI. MATERIAL AND METHODS Forty adult Wistar albino rats were randomized into five groups: control, SCI alone (50 g/cm weight drop), methylprednisolone sodium succinate (MPSS) (30 mg/kg), curcumin + dimethyl sulfoxide (DMSO) (300 mg/kg), and DMSO alone (0.1 mg/kg). RESULTS Administration of curcumin significantly decreased LPO in first 24 hours. However, there were no differences in the neurological scores of injured rats between the medication groups and the control group. Curcumin was more effective than DMSO and MPSS in reducing LPO, whereas DMSO was more effective than curcumin and MPSS in minimizing ultrastuctural changes. The results of this study indicate that curcumin exerts a beneficial effect by decreasing LPO and may reduce tissue damage. CONCLUSION Since ultrastructural and neurological findings does not support biochemical finding, our findings do not exclude the possibility that curcumin has a protective effect on the spinal cord ultrastructure and neurological recovery after SCI. A combination of curcumin with other vehicle may also have a considerable synergy in protecting spinal cord.

Effect of local use of L-carnitine after myringotomy on myringosclerosis development in rats.

OBJECTIVES This study aimed to investigate the effect of local and intraperitoneal administration of L-carnitine on the prevention of experimentally induced myringosclerosis, and to compare treatment efficiency. METHODS Twenty-four Albino-Wistar rats (48 ears) were bilaterally myringotomised and divided randomly into four groups: group one received no treatment, group two received intraperitoneal L-carnitine, group three received local L-carnitine, and group four received both intraperitoneal and local L-carnitine. On the 15th day after treatment, tympanic membranes were harvested and evaluated histopathologically for myringosclerotic plaque formation, fibroblastic proliferation, tympanic membrane thickness and new vessel formation. RESULTS The group one tympanic membranes showed extensive thickness, and the incidence of myringosclerosis and fibroblast proliferation were greater than in groups two and four. There were statistically significant differences in tympanic membrane thickness between groups three and four, and in myringosclerosis incidence and fibroblast proliferation, comparing groups two, three and four. CONCLUSION Myringosclerosis development was significantly reduced in rats receiving myringotomy plus intraperitoneal L-carnitine. Intraperitoneal L-carnitine administration prevented fibroblastic proliferation and tympanic membrane thickening (both of which cause further tympanic membrane destruction), thus reducing myringotomy-associated morbidity. Local L-carnitine administration had limited effectiveness in this experimental setting.

Topiramate attenuates hippocampal injury after experimental subarachnoid hemorrhage in rabbits

Abstract Objective: The aim of this study was to investigate the ability of topiramate (TPM) to prevent neural injury in a rabbit model of subarachnoid hemorrhage (SAH). The effect of TPM on cerebral vasospasm was also evaluated. Methods: Fifty-three New Zealand white rabbits were allocated into three groups randomly. SAH was induced by injecting autologous blood into the cisterna magna. The treatment groups were as follows: (1) sham operated (no SAH (n=18); (2) SAH only (n=17); (3) SAH + TPM (n=18). Hippocampal sections were evaluated for neural tissue degeneration, using the previously described neural degeneration scoring system. The ApopTag peroxidase in situ apoptosis detection kit (Serologicals Corp., former Intergen) was used to assess apoptosis in the hippocampal sections and the effect of TPM on the apoptotic response. Basilar artery lumen areas and arterial wall thickness were also measured in all groups. Results: There was a statistically significant difference between the mean degeneration scores of the control and SAH only groups (p<0.05). The level of neural degeneration in TPM treated group was significantly lower compared with SAH only group (p<0.05), but not significantly higher than the control group (p>0.05). There were no statistically significant differences between arterial cross-sectional area and arterial wall thickness measurements of the SAH group and SAH + TPM group. Conclusion: These findings demonstrate that TPM has marked neuroprotective effect in an experimental model of SAH in rabbits. This observation may have clinical implications suggesting that this antiepileptic drug could be used as a possible neuroprotective agent in patients without major adverse effects.

Imaging and surgical outcomes of spinal tumors in 18 dogs and one cat

Clinical and magnetic resonance imaging (MRI) findings, histological appearances and surgical outcomes of 18 dogs and one cat with spinal tumors are presented. Medical records of the cases admitted for spinal disorders were reviewed, and cases of spinal tumors that were diagnosed by MRI and confirmed by histological examination were included in this study. T1 weighted, T2 weighted and contrast enhanced T1 weighted images were taken and interpreted to evaluate the spinal tumors. The tumors were diagnosed as: meningioma (n = 6), ependymoma (n = 1), nerve sheath tumor (n = 4), metastatic spinal tumor (n = 3), osteosarcoma (n = 2), osteoma (n = 1), rhabdomyosarcoma (n = 1), and nephroblastoma (n = 1). Thirteen cases underwent surgical operation and the remaining six cases were euthanized at the request of the owners. The neurological status of the surgical cases did not deteriorate, except for one dog that showed ependymoma in the early period after the operation. These results indicate the potential for surgical gross total tumor removal of vertebral tumors to provide better quality of life and surgical collection of histological specimens for definitive diagnosis. For effective case management, dedicated MRI examination is important to accurate evaluation of the spinal tumors, and surgical treatment is useful for extradural and intradural-extramedullary spinal tumors.

Intraspinal Transplantation of Autologous neurogenically-Induced Bone Marrow-Derived Mesenchymal Stem Cells in the Treatment of Paraplegic Dogs without Deep Pain Perception Secondary to Intervertebral Disk Disease

AIM To investigate the effects of neurogenically-induced autologous bone marrow-derived mesenchymal stem cells (NIBM-MSCs) in paraplegic dogs without deep pain perception (DPP) secondary to intervertebral disk disease (IVDD). MATERIAL AND METHODS Seven dogs which could not be improved neurologically with conventional treatment modalities were included in the study. All dogs were diagnosed by magnetic resonance imaging and surgically treated. Each dog received two times a suspension of autologous 5.0x106 NIBM-MSCs, which were positive to CNPase and MAP-2, as well as to GFAP and beta III tubulin into the spinal cord through the hemilaminectomy defect percutaneously, with a 21-day interval. RESULTS Two months after cell transplantation, there were no changes except for 1 gait score improvement for 1 of the cases. At the 4th month, gait score had improved 1 score in 5 cases, and one score progress was recorded in proprioception and nociception in 1 case. In eight months-followed up 4 cases were evaluated by the same parameter; gait score had improved in 3 cases, and propriception improved in 2 cases, and nociception improved in 3 cases. CONCLUSION Our findings suggest that utility of autologous NIBM-MSCs for cases with poor prognosis after IVDD can be a promising approach.

Nasca classification of hemivertebra in five dogs

Five dogs, four small mixed breed and a Doberman Pinscher, presented in our clinic with hemivertebra. Complete physical, radiological and neurological examinations were done and the spinal deformities were characterized in accord with the Nasca classification used in human medicine. Two dogs had multiple hemivertebrae (round, oval or wedge-shaped: Type 3) in the thoracic region; one dog had an individual surplus half vertebral body (Type 1) plus a wedge-shaped hemivertebra (Type 2b) in the lumbar region; one dog had multiple hemivertebrae which were fused on one side (Type 4a) in the thoracic region; and one dog had a wedge-shaped hemivertebra (Type 2a) in the cervical region.

Effects of carbamazepine on spinal cord ischemia

BACKGROUND Prophylactic treatment with carbamazepine has been shown to reduce the cerebral damage and neurologic deficit in ischemic conditions. A randomized controlled study based on a rabbit model was designed to study the effect of carbamazepine on a spinal cord ischemic reperfusion injury. METHODS Thirty New Zealand rabbits were randomly assigned to 1 of the 2 groups (n = 15 per group): group I (control group) and group II (carbamazepine group). Spinal cord ischemia was induced by infrarenal aortic crossclamp for 25 minutes in both groups. Functional evaluation with the Tarlov score during a 2-day observation period and histopathologic assessment of the lumbar spinal cord were performed. Changes in spinal cord morphology were observed with hematoxylin-eosin staining and electron microscopy. Gray matter damage was assessed on the basis of the number of normal neurons in the ventral horn. RESULTS Diffuse destruction of gray matter with moderate to severe vacuolization and essentially no normal ganglion cells was observed in the spinal cord of rabbits in the control group, whereas specimens of rabbits assigned to the carbamazepine group showed ganglion cells with normal nuclei and cytoplasm (P < .0001). Neurologic impairment was significantly attenuated in the carbamazepine group compared with the Tarlov scores of the control group (P < .0001 at day 2). CONCLUSION Carbamazepine may protect the spinal cord from ischemic reperfusion injury that is associated with ameliorated neurologic and histopathologic results.