Neuroprotective Effects of Milrinone on Experimental Acute Spinal Cord Injury: Rat Model.

OBJECTIVE: Spinal cord injury (SCI) disrupts nerve axons with devastating neurological consequences, but there is no effective clinical treatment. The secondary damage mechanism is a mainstay process, and it starts within a few minutes after trauma. We aim to investigate the neuroprotective effects of milrinone on the SCI model. MATERIALS AND METHODS: A total of 36 Wistar albino rats, each weighing 300-400 g, were randomly split into 4 groups that received different treatments: in group 1 (sham) (n = 9) control, only a laminectomy was performed; in group 2 (SCI) (n = 9), SCI was imitated after laminectomy; in group 3 (SCI + saline) (n = 9), physiological saline solution was injected intraperitoneally immediately after the SCI; and in group 4 (SCI + milrinone), milrinone was administered intraperitoneally on lateral decubitus position immediately after the SCI. Spinal cord contusion was established by the weight-drop technique after laminectomy. Neurological examination scores were recorded, and rats were killed 72 hours later. Serum and spinal cord tissue glutathione peroxidase, total antioxidant status, total oxidant status, 8-hydroxiguanosine, interleukin-6 and interleukin-10 levels, histopathological spinal cord damage score, and apoptotic index were examined and compared between groups. RESULTS: Neurological examination scores were significantly better in the milrinone-treated group compared with groups 2 and 3. SCI significantly increased serum and spinal cord tissue glutathione peroxidase, total oxidant status, 8-hydroxiguanosine, and interleukin-6 levels that were successfully reduced with milrinone treatment. Interleukin-10 and total antioxidant status levels decreased as a result of SCI increased with milrinone treatment. Increased histopathological spinal cord damage score and apoptotic index in groups 2 and 3 significantly decreased in group 4. CONCLUSIONS: Milrinone could reduce apoptosis and increase anti-inflammatory and antioxidative mediators, thus playing a protective role in secondary nerve injury after SCI in rats.

Ameliorating the effects of Adalimumab on rabbits with experimental cerebral vasospasm after subarachnoid hemorrhage.

BACKGROUND: Adalimumab (ADA), which is a new-generation recombinant human monoclonal antibody for tumor necrosis factor α (TNFα), has strong anti-inflammatory effects. The role of enhanced inflammation is well established for the development and progression of cerebral vasospasm. Investigated in the present study is the probable ameliorating and neuroprotective effects of ADA in rabbits using a cerebral vasospasm model with biochemical and histopathological methods. METHODS: Thirty male New-Zealand white rabbits were randomly divided into control, subarachnoid hemorrhage (SAH) only and SAH plus ADA treatment groups. SAH was established as a single cisterna magna autologous arterial blood injection. ADA treatment was started just after intracisternal blood injection and continued for 72 hours once a day. The animals were sacrificed 72 hours after the induction of SAH, serum and brainstem tissue obtained for investigations. RESULTS: Brainstem tissue and plasma levels of tumor necrosis factor-alpha and Interleukin-1ß, brainstem tissue Matrix metalloproteinase-9 levels increased after SAH and partly decreased after treatment. Plasma levels of brain-derived neurotrophic factor decreased after SAH and partly restored after treatment. ADA treatment significantly increased the mean cross-sectional area of the vasospastic basilar arteries, reduced the basilar artery wall thickness and also ameliorates enhanced endothelial apoptosis. CONCLUSION: Findings obtained in this study suggest that ADA is an effective neuroprotective agent for ameliorating cerebral vasospasm in experimental rabbit vasospasm.

The effects of steroids in traumatic thoracolumbar junction patients on neurological outcome.

BACKGROUND: In this study, we aim to evaluate the potential effects of methylprednisolone on the neurological outcome of spinal cord injury (SCI) patients with thoracolumbar junction (T10-L1) spine fractures. METHODS: The data from 182 SCI patients who sustained a thoracolumbar junction spine fracture were operated by us between September 2008 to January 2015 were analysed retrospectively. The patients were divided into two groups: Group 1 underwent methylprednisolone treatment in conjunction with early surgical intervention, while group 2 underwent only early surgical intervention without methylprednisolone treatment. American Spinal Injury Association (ASIA) motor index scores of the patients were evaluated and compared with statistical methods at admission and at the first-year follow-up. RESULTS: The main follow-up period was 14.4±1.4 months in group 1 and 13.6±1.7 months in group 2. Initial and last follow-up ASIA scores of the patients were similar between groups (p>0.05), but the complication rate was significantly high in group 1 (p<0.05). CONCLUSION: The findings showed that steroids have no significant beneficial effects on the neurological outcome but have significant side effects and leads to increased complication rate in SCI patients.

Neuroprotective Effects of Tocilizumab on Experimentally-Induced Spinal Cord Ischemia-Reperfusion Injury.

OBJECTIVES: We aimed to evaluate neuroprotective effects of tocilizumab on spinal cord ischemia-reperfusion (I/R) injury. Our study design was an experimental rabbit spinal cord I/R injury model, and the setting was at the Animal Research Laboratory, Necmettin Erbakan University, Meram School of Medicine, Konya, Turkey. METHODS: Twenty-four adult New Zealand rabbits were randomly divided into 3 groups: Group 1, control group (n = 8); Group 2, I/R group, and Group 3 (n = 8) I/R injury + tocilizumab (4 mg/kg, ip) treatment group. Spinal cord I/R injury repair was performed by infrarenal aortic cross clamping. On neurologic evaluation, spinal cord tissue plasma tumor necrosis factor alpha (TNFα), total antioxidant status (TAS), total oxidant status (TOS), thiobarbituric acid reactive substances (TBARS), interleukin 6 (IL-6), interleukin 10 (IL-10) levels were analyzed. Spinal cord neuronal damage score and apoptotic cell count were also investigated. RESULTS: I/R injury significantly increases the plasma and spinal cord tissue TNFα, TOS, TBARS, and IL-6 levels and decreases the plasma and spinal cord tissue TAS and IL-10 levels. Tocilizumab treatment significantly reduces the plasma and spinal cord tissue TNFα, TOS, TBARS, IL-6 levels and increases plasma and tissue TAS and IL-10 levels. I/R injury significantly increases spinal cord neuronal damage score and apoptotic cell count. Tocilizumab treatment significantly reduces spinal cord neuronal damage score and apoptotic cell count. Neurologic examination scores at 24, 48, and 72 hours were significantly better in the treatment group when compared with the I/R group. CONCLUSIONS: This study shows significant neuroprotective effects of tocilizumab on rabbit spinal cord I/R injury.

Morphometric Analysis of the Sacral Canal and Hiatus Using Multidetector Computed Tomography for Interventional Procedures.

AIM: The sacral canal has been frequently used as "a passage" for minimally invasive diagnostic and therapeutic procedures for spinal diseases. The aim of the present study was to investigate morphometric analyses of the sacral canal, hiatus, and surrounding structures according to different age groups and gender by using the "multidetector computed tomography" method. MATERIAL AND METHODS: Multiplanar-reconstructed images from 300 adult (150 females and 150 males, between 20 and 80 years old) were divided into three groups according to age and retrospectively examined. Various anatomic measurements of the sacral hiatus, surrounding structures, and sacral canal were performed. Sacral curvature angle and lumbosacral lordotic angle were noted. RESULTS: Bony anatomic abnormalities such as absent hiatus (0.3%), complete agenesis (1%), and bony septum (2.6%) were detected in some cases. The anteroposterior (AP) diameter of the hiatus was less than 2 mm in 5% of cases. In all groups, the mean values of the hiatus AP diameter and area, and the shortest distance of the sacral canal AP diameter were shorter in the 60-80 years age group when compared with those in 20-39 years age group (p=0.01). The shortest sacral canal AP diameter was commonly located at the S2 and S3 levels in 59.2% and 33.9% of cases, respectively. The levels of maximum curvature were at S3 and S2 in 63.3% and 26.7% of cases, respectively. Median sacral curvature angles and lumbosacral lordotic angles were measured as 164° and 134°, respectively. CONCLUSION: Sacral structures have morphometric variations. Understanding of the detailed anatomy may improve the reliability of interventional procedures.

The effects of alpha lipoic acid on cerebral vasospasm following experimental subarachnoid hemorrhage in the rabbit.

AIM: The aim of this study is to determine the effects of a strong dithiol antioxidant, alpha lipoic acid (ALA) on cerebral vasospasm following subarachnoid hemorrhage in a rabbit model. MATERIAL AND METHODS: Twenty-one New Zealand white rabbits were assigned to one of three groups: group 1 (control), group 2 (SAH only), group 3 (SAH+ALA). ALA was administered (100 mg/kg/day, single dose, intraperitoneally). The rabbits were sacrificed 72 hours after SAH. The basilar artery lumen areas, arterial wall thickness and endothelial apoptosis in a cross section of basilar artery were measured in all groups. The tissue MDA, SOD, GSH-Px levels were also determined. RESULTS: The elevated tissue MDA levels after SAH were significantly reduced by ALA treatment. The reduced tissue SOD and GSH-Px levels after SAH were also elevated by ALA treatment. In the treatment group the average wall thickness and the mean percentages of apoptotic cells (apoptotic index) were reduced and the average cross-sectional areas of the basilar artery were increased statistically significantly. CONCLUSION: ALA treatment attenuates the severity of cerebral vasospasm by its strong antioxidant, antivasospastic and antiapoptotic properties. ALA may potentially serve as agents in the prevention of cerebral vasospasm after SAH.

The role of intravenous immunoglobulin in the treatment of cerebral vasospasm induced by subarachnoid haemorrhage: an experimental study.

OBJECTIVES: The aim of this study was to determine whether intravenous immunoglobulin (IVIG) prevents cerebral vasospasm in rabbits with induced subarachnoid haemorrhage (SAH). The effect of IVIG on apoptosis in the endothelial cells of the basilar artery was also evaluated. METHODS: Eighteen New Zealand white rabbits were allocated randomly into three groups. SAH was induced by injecting autologous blood into the cisterna magna. Group 1, the control group, was subjected to sham surgery (no induction of SAH). Group 2 had SAH alone and Group 3 had SAH plus IVIG. Three days after treatment, the animals were sacrificed. The basilar artery tissues were analysed histologically and the malondialdehyde levels in the brain stem tissues were evaluated biochemically. RESULTS: Differences in the histopathological luminal areas and full wall thicknesses in the SAH plus IVIG group and the SAH group were statically insignificant (p > 0.005). The malondialdehyde level was also found to be lower in the IVIG group than in the SAH group, although this difference was not significant (p > 0.005). CONCLUSION: Although the IVIG treatment was revealed to have no vasodilator effect on the SAH-induced spastic basilar artery, it was shown to have a beneficial effect on the apoptosis of endothelial cells, probably via anti-inflammatory mechanisms.

Beneficial effects of levosimendan on cerebral vasospasm induced by subarachnoid haemorrhage: an experimental study.

BACKGROUND: The aim of this study was to investigate the ability of levosimendan to prevent cerebral vasospasm in a rabbit model of subarachnoid haemorrhage (SAH). ANIMALS AND METHODS: Eighteen New Zealand white rabbits were allocated into three groups randomly. SAH was induced by injecting autologous blood into the cisterna magna. (Group 1 = control:sham surgery group, Group 2 = SAH alone group, Group 3 = SAH plus levosimendan group). Histopathological examination was performed on day 3 as described. Intravenous levosimendan dose (initially 12 microg kg(-1) infusion, continuously for at least 10 minutes and then continued with a dose of 0.2 microg kg(-1) min(-1)) treatment was started after the induction of SAH. Three days later, the animals were sacrificed. RESULTS: In pathological investigation; there was statistically significant difference in luminal area and muscular wall thickness of the basilar artery between all groups (p < 0.005). Malondialdehyde level was also found significantly low in the levosimendan group compared with the SAH group. CONCLUSION: Intravenous levosimendan treatment was found effective by increasing the pathological luminal area and reducing muscular wall thickness measurements. This is the first study to show that intravenous administration of levosimendan is effective in preventing cerebral vasospasm induced by SAH in rabbits.