Effects of 4% Icodextrin on Experimental Spinal Epidural Fibrosis.

AIM: The aim of this experimental study was to investigate whether spinal epidural 4% glucose polymer solution is effective in the prevention of postoperative fibrosis. MATERIAL AND METHODS: Twenty eight adult Wistar albino rats were randomly divided into two equal groups, including treatment and control. Both groups underwent L1 vertebral total laminectomy to expose the dura. Topical treatment group received 4% icodextrin. Four weeks later, epidural fibrosis was examined in both groups histologically, biochemically and macroscopically. RESULTS: Topical use of 4% icodextrin prevented significantly epidural fibrosis following the laminectomy operation. CONCLUSION: Topical 4% icodextrin application inhibits postoperative epidural fibrosis with various mechanisms and prevents adhesions by playing barrier role between tissue surfaces through flotation. Our study is first to present evidence of experimental epidural fibrosis prevention with 4% icodextrin.

Hemostasis vs. epidural fibrosis?: A comparative study on an experimental rat model of laminectomy.

AIM: The aim of this study was to evaluate the histopathological and biochemical impact and effectiveness of two hemostatic agents, Ankaferd blood stopper (ABS) and Microporous Polysaccharide Hemospheres (MPH), on epidural fibrosis in an experimental rat laminectomy model. MATERIAL AND METHODS: Twenty adult Wistar albino rats were divided into MPH-treated (n=6), ABS-treated (n=6) and control (n=8) groups. Laminectomy of the lumbar spine was performed in all animals and treatment groups were exposed to MPH and ABS while closure was applied in control group as per usual. Epidural fibrosis was evaluated in all groups macroscopically, histopathologically, biochemically and with electron microscopy four weeks later. RESULTS: Statistically, it was found that MPH-treated group had significantly less epidural fibrosis compared to ABS-treated and control groups. CONCLUSION: We compared two hemostatic agents for their propensity to cause adhesions in the present study. Our results show that MPH significantly reduces epidural scar formation and dural adhesion in a rat model of laminectomy while ABS increases postoperative fibrosis.

Pentoxifylline Inhibits Epidural Fibrosis in Post-Laminectomy Rats.

BACKGROUND: The aim of this experimental study was to investigate the effectiveness of intramuscular pentoxifylline in the prevention of postoperative fibrosis. MATERIAL/METHODS: We divided 16 adult Wistar albino rats into 2 equal groups: treatment and control. Both groups underwent L1 vertebral total laminectomy to expose the dura. The intramuscular treatment group received pentoxifylline. Four weeks later, epidural fibrosis was studied in both groups using electron microscopy, light microscopy, histology, biochemistry, and macroscopy. RESULTS: The evaluation of epidural fibrosis in the 2 groups according to macroscopic (p<0.01) assessment and light microscopy revealed that epidural scar tissue formation was lower in the treatment group compared to the control group (p<0.001) and the number of fibroblasts was also decreased significantly in the pentoxifylline-treated group (p<0.05). More immature fibers were demonstrated in the treatment group by electron microscopy in comparison with the control group. In biochemical analysis, a statistically significant decrease was detected in hydroxyproline, which indicates fibrosis and myeloperoxidase activity, and shows an inflammatory response (P<0.001). CONCLUSIONS: Systemic pentoxifylline application prevents postoperative epidural fibrosis and adhesions with various mechanisms. Our study is the first to present evidence of experimental epidural fibrosis prevention with pentoxifylline.

The Effects of Difumarate Salt S-15176 after Spinal Cord Injury in Rats.

OBJECTIVE: In the present study we analyzed neuroprotective and antiapoptotic effect of the difumarate salt S-15176, as an anti-ischemic, an antioxidant and a stabilizer of mitochondrial membrane in secondary damage following spinal cord injury (SCI) in a rat model. METHODS: Three groups were performed with 30 Wistar rats; control (1), trauma (2), and a trauma+S-15176 (10 mg/kg i.p., dimethyl sulfoxide) treatment (3). SCI was performed at the thoracic level using the weight-drop technique. Spinal cord tissues were collected following intracardiac perfusion in 3rd and 7th days of posttrauma. Hematoxylin and eosin staining for histopatology, terminal deoxynucleotidyl transferase dUTP nick end labeling assay for apoptotic cells and immunohistochemistry for proapoptotic cytochrome-c, Bax and caspase 9 were performed to all groups. Functional recovery test were applied to each group in 3rd and 7th days following SCI. RESULTS: In trauma group, edematous regions, diffuse hemorrhage, necrosis, leukocyte infiltration and severe degeneration in motor neurons were observed prominently in gray matter. The number of apoptotic cells was significantly higher (p<0.05) than control group. In the S-15176-treated groups, apoptotic cell number in 3rd and 7th days (p<0.001), also cytochrome-c (p<0.001), Bax (p<0.001) and caspase 9 immunoreactive cells (p<0.001) were significantly decreased in number compared to trauma groups. Hemorrhage and edema in the focal areas were also noticed in gray matter of treatment groups. Results of the locomotor test were significantly increased in treatment group (p<0.05) when compared to trauma groups. CONCLUSION: We suggest that difumarate salt S-15176 prevents mitochondrial pathways of apoptosis and protects spinal cord from secondary injury and helps to preserve motor function following SCI in rats.

[Bilateral epidural hematoma in a patient with human immunodeficiency virus infection: a case report]. / Human immunodeficiency virus ile enfekte bir hastada gelisen iki tarafli epidural hematom: Olgu sunumu.

Intracranial epidural haematomas are almost always secondary to head traumas and usually occur unilaterally. Bilateral intracranial epidural haematomas are rare, but the mortality is very high. In our case, we report a bilateral epidural haematoma in a 32 year old, HIV infected male patient who came to the emergency service with a head trauma because of a motor vehicle-pedestrian accident. The occurrence of bilateral epidural haematoma in an HIV infected patient is a rare condition as a result of head trauma in a lateral direction on one side. As a result of the vasculopathy and coagulopathy, which are complications of HIV infection, the cerebral vessels have a fragile structure that leads to complications that facilitate the development of contralateral intracranial epidural haematoma together.

AR-A014418 as a glycogen synthase kinase-3 inhibitor: anti-apoptotic and therapeutic potential in experimental spinal cord injury.

OBJECTIVES: We aimed to investigate the effects of AR-A014418, a strong inhibitor specific to GSK-3beta, on neuronal apoptosis and neuroprotection in the traumatic SCI model. MATERIALS AND METHODS: In this study, three groups were generated from 36 Wistar rats; (1) control, (2) spinal cord trauma group created by clip compression technique after laminectomy, and (3) AR-A014418 (4mg/kg, i.p., DMSO) treatment group after laminectomy and spinal cord trauma. The TUNEL assay for apoptosis detection, immunohistochemical staining for bax and TGF-beta were applied in spinal cord tissues. For light microscopic examination, necrotic, and apoptotic cells were counted, and PMNL counting was applied to detect inflammation. Functional recovery was tested by field locomotor test in the 3rd and 7th days following surgery. RESULTS: In the trauma group, diffuse hemorrhage, cavitation, necrosis and edematous regions, degeneration in motor neurons and leukocyte infiltration were observed in gray matter. In the AR-A014418-treated groups, healthy cells were observed in more places compared to the trauma groups, however, cavitation, hemorrhagic, and edematous areas were seen in gray matter. In the AR-A014418-treatment groups, the number of apoptotic cells in the 3rd and 7th days (respectively; p<0.05, p<0.01), were significantly decreased compared to the trauma groups, as were the levels of bax (p<0.01) and TGF-beta 1 immunoreactivity. Results of the locomotor test were significantly increased in the treatment group (p<0.001) as compared to the trauma group. CONCLUSIONS: In this experimental spinal cord trauma model study neural apoptosis was significantly triggered in secondary damage developed after trauma, however, neurological healing was expedited by preventing mitochondrial apoptosis and reducing the inflammation by the potent inhibitor AR-A014418, which is GSK-3beta selective.

Pneumorrhachis associated with bronchial asthma, subcutaneous emphysema and pneumomediastinum.

Pneumorrhachis is defined as the presence of air in the epidural space or subarachnoid space. The air may migrate along fascial planes from the posterior mediastinum, through the neural foramina, and into the epidural space. Pneumorrhachis is rare, and even more so in the paediatric population. Pneumorrhachis in itself usually is asymptomatic, does not tend to migrate and reabsorbs spontaneously. The combination of pneumomediastinum with epidural pneumorrhachis without thoracic trauma has rarely been reported in the literature. The present case report describes the presence of pneumomediastinum, subcutaneous emphysema, and pneumorrhachis in a child asthmatic patient who had a history of fever, violent cough.

Correlation between leptin and pro-inflammatory cytokines in cortical contusion injury model.

BACKGROUND: The present study aimed to investigate time-dependent changes in leptin concentrations in brain tissue following experimental traumatic brain injury and to examine the relationship with cytokines. METHODS: After circular craniectomy, 33 male Wistar-albino rats were positioned on a stereotaxic frame and subjected to cortical contusion injury and then divided into 3 groups based on the depth of deformation as: 0 mm (sham controls, n=3), 1.5 mm (moderate injury, n=15) and 2.7 mm (severe injury, n=15). Animals were sacrificed on the 1st, 3rd and 5th days post-injury. RESULTS: One day after moderate injury, interleukin-1 beta (IL-1ß), IL-6, tumor necrosis factor-alpha (TNF-?), and leptin levels were found to be markedly increased in the brain tissue. On the 3rd and 5th days, the levels returned to the shamcontrol levels. Following severe injury, IL-1ß, IL-6 and TNF-? levels increased in correlation after the 1st day and reached the sham-control levels on the same days. However, leptin tissue levels decreased on the 1st and 3rd days and normalized to the sham-control levels on the 5th day. CONCLUSION: Our results showed that the release of leptin is decreased in the early stage of severe injury. Thus, leptin replacement may play an important role in therapy in cases with severe traumatic brain injury.

A rare emergency condition in neurosurgery: foot drop due to Paget's disease.

Paget's disease is a chronic, focal skeletal disorder that usually affects the pelvis and spine. Spinal cases are generally asymptomatic; in the symptomatic cases, the neurological dysfunctions are related to non-compressive vascular defects, hemorrhage, sarcomatoid degeneration, spinal stenosis, or pathological fractures, primarily in the lumbar region. The Neurosurgeon should have a fundamental understanding of the complications of Paget's disease and should be familiar with the indications for treatment, as well as available medical and surgical therapies. In the present paper, we report a case of Paget's disease that presented with an isolated foot drop due to a pathological fracture of L5 vertebra, and then discuss the therapeutic strategies presented in the literature.

Therapeutic efficacy of SJA6017, a calpain inhibitor, in rat spinal cord injury.

Apoptosis is an important element of the secondary processes that occur after spinal cord injury. Calpain and caspases are key proteases in apoptotic cell death. We evaluated the neuroprotective effects of SJA6017 (a calpain inhibitor) and measured functional recovery in a rat spinal cord injury model. Thirty Wistar albino rats were divided into three groups of 10 animals each: sham-operated (group 1), trauma control (group 2) and trauma-plus-SJA6017 treatment (group 3). Spinal cord trauma was produced in the thoracic region of the animals. Rats in group 3 received SJA6017 1 min after trauma. Treatment efficacy was evaluated after injury using light microscopy and TUNEL staining. Neurological performance was assessed using an inclined plane and a modified version of the Tarlov's grading scale. Group 2 rats showed moderate trauma with widespread edema, hemorrhage, vascular thrombi and necrosis 24 h after injury. Group 3 rats had significantly reduced tissue injury and apoptosis. Tarlov scores revealed that group 3 rats also had ameliorated recovery of limb function. Our results demonstrate that treatment with SJA6017 reduces apoptotic cell death, preserves spinal cord tissue and improves functional outcome. Treating calpain-induced apoptosis with this agent may be a feasible therapeutic strategy for patients with spinal cord injury.

Therapeutic efficacy of Ac-DMQD-CHO, a caspase 3 inhibitor, for rat spinal cord injury.

We investigated the therapeutic efficacy of Ac-DMQD-CHO, a caspase-3 inhibitor, and functional recovery in spinal cord injury in a rat model. Thirty rats were randomized into three groups of 10 each. In groups 2 and 3, spinal cord trauma was produced in the thoracic region. Group 3 rats were treated with Ac-DMQD-CHO. Treatment responses were evaluated based on histopathological and TUNEL staining findings at 24 h and 5 days post-injury. Neurologic performance was assessed during and following treatment. Twenty-four hours after injury, light microscopy examination revealed diffuse hemorrhagic necrosis, edema, vascular thrombi, and polymorphonuclear leukocyte infiltration in group 2 and 3 rats, but cavitation and demyelinization were less prominent in group 3. At this time point, treatment of the rats with Ac-DMQD-CHO significantly reduced the number of apoptotic cells. Traumatic injury to the spinal cord causes apoptosis and administration of Ac-DMQD-CHO decreases apoptosis and improves functional outcome.

Tauroursodeoxycholic acid and secondary damage after spinal cord injury in rats.

Greater clinical understanding of the pivotal role of apoptosis in spinal cord injury (SCI) has led to new and innovative apoptosis-based therapies for patients with an SCI. Tauroursodeoxycholic acid (TUDCA) is a biliary acid with antiapoptotic properties. To our knowledge, this is the first study in the English language to evaluate the therapeutic efficacy of TUDCA in an experimental model of SCI. Thirty rats were randomized into three groups (sham-operated, trauma only, and trauma plus TUDCA treatment) of 10 each. In groups 2 and 3, spinal cord trauma was produced at the T8-T10 level via the Allen weight drop technique. Rats in group 3 were treated with TUDCA (200 mg/kg intraperitoneal) 1 min after trauma. The rats were killed either 24 h or 5 days after injury. The neuroprotective effect of TUDCA on injured spinal cord tissue and the effects of that agent on the recovery of hind-limb function were assessed. The efficacy of treatment was evaluated with histopathologic examination and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) analysis. Histopathologic characteristics were analyzed by comparison of hematoxylin-and-eosin stained specimens. Neurologic evaluations were performed 24 h, 3 days, and 5 days after trauma. Hind-limb function was assessed with the inclined plane technique of Rivlin and Tator and the modified version of Tarlov's grading scale. Twenty-four hours after injury, there was a significantly higher number of apoptotic cells in the lesioned spinal cord group than in the sham-operated control group. Treatment of the rats with TUDCA significantly reduced the number of apoptotic cells (4.52+/-0.30 vs. 2.31+/-0.24 in group 2) and the degree of tissue injury. Histopathologic examination showed that group 3 rats had better spinal cord architecture compared with group 2 rats. Five days after injury, the mean inclined plane angles in groups 1, 2, and 3 were 65.50 degrees +/- 2.09, 42.00 degrees +/- 2.74, and 53.50 degrees +/- 1.36. Motor grading of the rats revealed a similar trend. These differences were statistically significant (p<0.05). The mechanism of neuroprotection in the treated rats, although not yet elucidated, may be related to the marked antiapoptotic properties of TUDCA. A therapeutic strategy using TUDCA may eventually lead to effective treatment of SCI without toxic effects in humans.

Neuroprotective effects of Ac.YVAD.cmk on experimental spinal cord injury in rats.

BACKGROUND: Apoptosis as a cell death mechanism is important in numerous diseases, including traumatic SCI. We evaluated the neuroprotective effects of Ac.YVAD.cmk and functional outcomes in a rat SCI model. METHODS: Thirty rats were randomized into 3 groups of 10: sham-operated, trauma only, and trauma plus Ac.YVAD.cmk treatment. Trauma was produced in the thoracic region by a weight-drop technique. Group 3 rats received Ac.YVAD.cmk (1 mg/kg, ip) 1 minute after trauma. The rats were killed at 24 hours and 5 days after injury. Efficacy was evaluated with light microscopy and TUNEL staining. Functional outcomes were assessed with the inclined plane technique and a modified version of the Tarlov grading system. RESULTS: At 24 hours postinjury, the respective mean number of apoptotic cells in groups 1, 2, and 3 were 0, 5.26 +/- 0.19, and 0.97 +/- 0.15. Microscopic examination of group 2 tissues showed widespread hemorrhage, edema, necrosis, and polymorphic nuclear leukocyte infiltration and vascular thrombi. Group 3 tissues revealed similar features, but cavitation and demyelination were less prominent than those in group 2 samples at this period. At 5 days postinjury, the respective mean inclined plane angles in groups 1, 2, and 3 were 65.5 +/- 2.09, 42.00 +/- 2.74, and 52.5 +/- 1.77. Motor grading of animals revealed a similar trend. These differences were statistically significant (P < .05). CONCLUSIONS: Ac.YVAD.cmk inhibited posttraumatic apoptosis in a rat SCI model. This may provide the basis for development of new therapeutic strategies for the treatment of SCI.

The effects of resveratrol on vasospasm after experimental subarachnoidal hemorrhage in rats.

BACKGROUND: Cerebral vasospasm remains a major cause of morbidity and mortality in patients with SAH. Although many pharmacologic agents and chemicals have been used to prevent and treat CV, the pathogenesis of that condition has not been established. We investigated the efficacy of resveratrol, a stilbene polyphenol and tyrosine kinase inhibitor that occurs naturally in grapes and red wine, in a murine basilar artery vasospasm model. METHODS: Forty-two Wistar albino rats were used in this study. The rats were divided into 3 groups of 14 animals each: the sham-operated control group (group 1), the vasospasm group (group 2), and the treatment group (group 3). In groups 2 and 3, autologous blood (0.3 mL) was injected into the cisterna magna. After that injection, the rats in group 3 received an intravenous injection of resveratrol (10 mg/kg) for 72 hours. The evaluation of the response to both the injection of autologous blood and treatment was based on biochemical markers in tissue and serum and on light microscopic findings from the basilar artery, which were collected at different intervals after experimental SAH. RESULTS: Endothelin-1 levels in brain tissue and serum were higher in the vasospasm group than in the control group (P < .05). In group 3 rats, the administration of resveratrol resulted in significantly lower ET-1 values than those in group 2. Brain and serum lipid peroxidation levels were markedly elevated in group 2 rats but decreased significantly after resveratrol treatment in group 3 rats (P < .05). Superoxide dismutase expression in brain tissue and serum was lower in group 2 rats than in sham-operated controls, and a significant increase in the SOD level was associated with resveratrol treatment. On examination via light microscopy 72 hours after SAH, the mean perimeters of the arterial lumen in groups 1, 2, and 3 were 719 +/- 16, 411.6 +/- 9, and 590.1 +/- 5.6 microm, respectively. The mean thickness of the arterial wall was as follows: in group 1, 11.1 +/- 0.8 microm; in group 2, 16.1 +/- 1.2 microm; and (after resveratrol treatment) in group 3, 13.4 +/- 0.6 microm. CONCLUSIONS: The results of our study showed that resveratrol induced the relaxation of smooth muscle in the wall of the basilar artery and may be provided with neuroprotection against cerebral ischemia in a rat model. These effects may be associated with the antioxidant and vasodilatory effects of resveratrol, which could prove to be an agent prophylactic against CV and to be therapeutic for individuals who experience that event.

The neuroprotective effects of z-DEVD.fmk, a caspase-3 inhibitor, on traumatic spinal cord injury in rats.

BACKGROUND: Apoptosis is one of the most important forms of cell death seen in a variety of physiological and pathological conditions, including traumatic injuries. This type of cell death occurs via mediators known as caspases. Previous studies have investigated the roles that apoptosis and different caspases play in the pathogenesis of secondary damage after spinal cord injury (SCI). The aim of this research was to assess the neuroprotective effect of z-DEVD.fmk, a caspase-3 inhibitor, in a rat model of SCI. METHODS: Forty-five Wistar albino rats were studied in 3 groups of 15 animals: sham-operated control animals (group 1); trauma-only control animals (group 2); and rats subjected to trauma + z-DEVD.fmk treatment (group 3). Spinal cord injury was produced at the thoracic level using the weight-drop technique. Responses to injury and the efficacy of z-DEVD.fmk were assessed by light microscopy and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining in cord tissues collected at 4 and 24 hours posttrauma. Five rats from each group were used to assess functional recovery at 7 days after SCI. The functional evaluations were done using the inclined-plane technique and a modified Tarlov motor grading scale. RESULTS: At 4 hours postinjury, the mean apoptotic index in groups 1, 2, and 3 was 0, 33.01+/-6.62, and 16.40+/-4.91, respectively. The group 3 count was significantly lower than the group 2 count (P<.01). At 24 hours postinjury, light microscopic examination of group 2 tissues showed widespread hemorrhage, necrosis, polymorphonuclear leukocyte infiltration, and vascular thrombi. The group 3 tissues showed similar features. The prominent findings in group 2 were hemorrhage and necrosis, whereas the prominent findings in group 3 were focal hemorrhage and leukocyte infiltration. The mean inclined-plane angles in groups 1, 2, and 3 were 64.5 degrees+/-1.0 degrees, 41.5 degrees+/-1.3 degrees, and 47 degrees+/-2.0 degrees, respectively. Motor scale results in all groups showed a similar trend. CONCLUSION: Local application of z-DEVD.fmk after SCI in rats reduces secondary tissue injury and helps preserve motor function. These effects can be explained by inhibition of apoptotic death in all cell types in the spinal cord.

Neuroprotection and functional recovery after application of the caspase-9 inhibitor z-LEHD-fmk in a rat model of traumatic spinal cord injury.

OBJECT: Apoptosis is considered one of the most significant mechanisms in the pathogenesis of neuronal damage after spinal cord injury (SCI). This form of cell death occurs via mediators known as caspases. The aim of this study was to evaluate the neuroprotective effect of the caspase-9 inhibitor, z-LEHD-fmk, in a rat model of spinal cord trauma. METHODS: Fifty-four Wistar albino rats were studied in the following three groups of 18 animals each: sham-operated controls (Group 1); trauma-only controls (Group 2); and trauma combined with z-LEHD-fmk-treated animals (0.8 microM/kg; Group 3). Spinal cord injury was produced at the thoracic level by using the weight-drop technique. Responses to SCI and the efficacy of z-LEHD-fmk treatment were determined on the basis of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining and light and electron microscopy findings in cord tissue at 24 hours and 7 days posttrauma. Six rats from each group were also assessed for functional recovery at 3 and 7 days after SCI. This was conducted using the inclined-plane technique and a modified version of the Tarlov motor grading scale. At 24 hours postinjury, light microscopic examination of Group 2 tissue samples showed hemorrhage, edema, necrosis, polymorphonuclear leukocyte infiltration, and vascular thrombi. Those obtained in Group 3 rats at this stage showed similar features. At 24 hours postinjury, the mean apoptotic cell count in Group 2 was significantly higher than that in Group 3 (90.25 +/- 2.6 and 50.5 +/- 1.9, respectively; p < 0.05). At 7 days postinjury, the corresponding mean apoptotic cell counts were 49 +/- 2.1 and 17.7 +/- 2.6, also a significant difference (p < 0.05). Electron microscopy findings confirmed the occurrence of programmed cell death in different cell types in the spinal cord and showed that z-LEHD-fmk treatment protected neurons, glia, myelin, axons, and intracellular organelles. CONCLUSIONS: Examination of the findings in this rat model of SCI revealed that apoptosis occurs not only in neurons and astrocytes but also in oligodendrocytes and microglia. Furthermore, immediate treatment with the caspase-9 inhibitor z-LEHD-fmk blocked apoptosis effectively and was associated with better functional outcome. More in-depth research of the role of programmed cell death in spinal cord trauma and further study of the ways in which caspases are involved in this process may lead to new strategies for treating SCI.