Ayhan Kocak

Central nervous system protection by resveratrol in streptozotocin-induced diabetic rats

The objective of the present study was to investigate the possible neuroprotective effect of resveratrol against streptozotocin-induced hyperglycaemia in the rat brain and medulla spinalis. Thirty adult male Wistar rats were divided into three groups as follows: control group, streptozotocin-induced diabetic-untreated group, and streptozotocin-induced diabetic resveratrol-treated group. Diabetes was induced by a single injection of streptozotocin (STZ) (60 mg/kg body weight). Three days after streptozotocin injection, resveratrol (10 mg/kg) was injected intraperiteonally daily over 6 weeks to the rats in the treatment group. Six weeks later, seven rats from each group were killed and the brain stem and cervical spinal cord were removed. The hippocampus, cortex, cerebellum, brain stem and spinal cord were dissected for biochemical studies (lipid peroxidation measuring malondialdehyde [MDA], xanthine oxidase [XO], nitric oxide [NO] and glutathione). MDA, XO and NO levels in hippocampus, cortex, cerebellum, brain stem and spinal cord in the streptozotocin-induced diabetic-untreated group increased significantly. Treatment with resveratrol significantly reduced MDA, XO and NO production and increased glutathione levels when compared to the streptozotocin-induced diabetic-untreated group. This study demonstrates that resveratrol is a potent neuroprotective agent against diabetic oxidative damage.

Comparative neuroprotective effect of sodium channel blockers after experimental spinal cord injury.

Spinal cord injury (SCI) results in loss of function below the lesion. Secondary injury following the primary impact includes a number of biochemical and cellular alterations leading to tissue necrosis and cell death. Influx of Na(+) ions into cells has been postulated to be a key early event in the pathogenesis of secondary traumatic and ischemic central nervous system injury. Previous studies have shown that some voltage-sensitive sodium channel blockers provide powerful neuroprotection. The purpose of the present study was to compare the neuroprotective effect of three sodium channel blockers-mexiletine, phenytoin and riluzole--after SCI. Ninety rats were randomly and blindly divided into five groups of 18 rats each: sham-operated group, trauma group (bolus injection of 1 mL physiological saline intraperiteonally [i.p.]), mexiletine treatment group (80 mg/kg, i.p.), phenytoin treatment group (200 mg/kg, i.p.) and riluzole treatment group (8 mg/kg, i.p.). Twenty-four hours after injury, the rats were killed for determination of spinal cord water content and malondialdehyde (MDA) levels. Motor function scores of six rats from each group were evaluated weekly for six weeks. Then the rats were killed for histopathological assessment. Although all the treatment groups revealed significantly lower MDA levels and spinal cord edema than the trauma group (p<0.05), the riluzole and mexiletine treatment groups were better than the phenytoin treatment group. In the chronic stage, riluzole and mexiletine treatment achieved better results for neurobehavioral and histopathological recovery than phenytoin treatment. In conclusion, all the tested Na(+) blockers had a neuroprotective effect after SCI; riluzole and mexiletine were superior to phenytoin.

Effects of resveratrol and methylprednisolone on biochemical, neurobehavioral and histopathological recovery after experimental spinal cord injury

AbstractAim:To investigate the neuroprotective effect of resveratrol in an experimental spinal cord injury (SCI) model in rats.Methods:Male Wistar albino rats weighing 200–250 g were randomized into six groups. Weight-drop trauma was performed for SCI. Group 1 underwent laminectomy alone. Group 2 underwent laminectomy followed by SCI. Groups 3, 4, 5, and 6 underwent laminectomy followed by SCI and received resveratrol (100 mg/kg), methylprednisolone (MP) (30 mg/kg), resveratrol (100 mg/kg) plus MP (30 mg/kg), and ethanol (2%), respectively. The rats were divided into two subgroups for biochemical analysis (killed at 24 h after surgery) and for neurobehavioral and histopathological evaluation (killed at 6 weeks after surgery). Posttraumatic neurological recovery after surgery was recorded weekly.Results:Groups 3 and 5 revealed significantly lower malondialdehyde, nitric oxide, xanthine oxidase, and higher glutathione levels than group 4 (P<0.05). Neurological recovery rates were significantly better in groups 3 and 5 than group 4 (P<0.05). When spinal trauma size ratios were compared, there was no significant difference between treatment groups.Conclusion:Resveratrol treatment revealed better biochemical recovery in the acute stage of trauma than MP treatment. Although resveratrol and combined treatment revealed better neurobehavioral recovery than MP treatment; resveratrol, MP, and combined treatment modalities improved histopathological recovery at the same level in the final stage of the experiment. Future studies involving different doses of resveratrol and different doses combinations with MP could promise better results as each drug has a different anti-oxidative mechanism of action.

Intraventricular solitary fibrous tumor: an unusual tumor with radiological, ultrastructural, and immunohistochemical evaluation: case report.

OBJECTIVE AND IMPORTANCEIntracranial solitary fibrous tumors have been described previously, but intraventricular solitary fibrous tumors are extremely rare. We present what is, to our knowledge, the first reported case of solitary fibrous tumor in the third ventricle. CLINICAL PRESENTATIONA 63-year-old man presented with weakness of his lower extremities and headaches. Computed tomography and magnetic resonance imaging of the brain revealed an enhancing mass in the posterior part of the third ventricle. INTERVENTIONThe tumor originated from the wall of the left internal cerebral vein and extended to the posterior part of the third ventricle. Nearly total excision was performed via an infratentorial-supracerebellar approach. CONCLUSIONThe differential diagnosis of intracranial solitary fibrous tumors includes fibroblastic meningioma, meningeal hemangiopericytoma, neurofibroma, and schwannoma. The differential diagnosis in the present case was greatly helped by the immunohistochemical and ultrastructural findings, along with a disease-free 3.5-year follow-up. These findings are presented with reference to previous reports.

Effect of combined treatment with melatonin and methylprednisolone on neurological recovery after experimental spinal cord injury

Spinal cord injury (SCI) results in the loss of function below the lesion. Secondary injury following the primary impact includes a number of biochemical and cellular alterations leading to tissue necrosis and cell death. Methylprednisolone (MP), by reducing edema and protecting the cell membrane against peroxidation, is the only pharmacological agent with a proven clinically beneficial effect on SCI. Melatonin, known as a free radical scavenger, has been shown to have an effect on lipid peroxidation following experimental SCI. The purpose of this study was to examine the effect of MP and melatonin on neurological, ultrastructural, and electrophysiological recovery. Female albino rats weighing 200–250 g were randomized into five groups of 18 rats each and six rats for the control group. Weight-drop trauma was performed for each group and a 30-mg/kg single dose of MP for rats in group 1, a 10-mg/kg single dose of melatonin for rats in group 2, and MP and melatonin in the same doses for rats in group 3 were administered immediately after trauma. The rats in group 4 were the vehicle group (treated with ethanol) and group 5 was the trauma group. The motor and somatosensory evoked potentials were recorded at the 4th hour, the 24th hour, and on the 10th day of the study for six rats in each group. Posttraumatic neurological recovery was recorded for 10 days using “motor function score” and inclined plane test. After electrophysiological study the rats were terminated for an analysis of lipid peroxidation level of the injured site of the spinal cord. Electron microscopic studies were performed to determine the effects of melatonin, MP, and the combined treatment with MP and melatonin on axons, neurons, myelin, nucleus, and intracytoplasmic edema. The groups treated with MP, melatonin, and a combination of both had significantly enhanced electrophysiological, biochemical, and neurological recovery and also showed better ultrastructural findings than the trauma and vehicle groups. Although combined treatment was significantly more effective on lipid peroxidation than melatonin or MP treatments alone, at the 10th day, neurobehavioral, electrophysiological, and ultrastructural recovery were at the same level. In conclusion, MP, melatonin, and MP and melatonin combined treatment modalities improved functional recovery at the same level. Future studies involving different doses of melatonin and different dose combinations with MP could promise better results since each drug has a different antioxidative mechanism of action.

A New Model for Tethered Cord Syndrome: A Biochemical, Electrophysiological, and Electron Microscopic Study

In order to investigate the pathophysiology of the tethered cord syndrome, a few experimental models have been developed and used previously. In this study, the authors present a new experimental model to investigate the biochemical, electrophysiological, and histopathological changes in the tethered spinal cord syndrome. A model was produced in guinea pigs using an application of cyanoacrylate to fixate the filum terminale and the surrounding tissue to the dorsal aspect of the sacrum following 5-gram stretching of the spinal cord. The experiments were performed on 40 animals divided into two groups. The responses to tethering were evaluated with hypoxanthine and lipid peroxidation, somatosensory and motor evoked potentials, and transmission electron microscope examination. The hypoxanthine and lipid peroxidation levels significantly increased, indicating an ischemic injury (p < 0.01). The average hypoxanthine level in the control group was 478.8 +/- 68.8 nmol/g wet tissue, while it was 651.2 +/- 71.5 nmol/g in the tethered cord group. The lipid peroxidation level in group I was 64.0 +/- 5.7 nmol/g wet tissue, whereas it was 84.0 +/- 4.7 nmol/g in group II. In the tethered cord group, the latencies of the somatosensory and motor evoked potentials significantly increased, and the amplitudes decreased. These changes indicated a defective conduction in the motor and sensorial nerve fibers. In the transmission electron microscopic examinations, besides the reversible changes like edema and destruction in the gray-white matter junction, irreversible changes like scarcity of neurofilaments and destruction in axons and damage in myelin sheaths were observed. We consider that this work can be used as an experimental model for tethered cord syndrome.

Effect of pinealectomy and melatonin replacement on morphological and biochemical recovery after traumatic brain injury

Numerous studies showed that melatonin, a free radical scavenger, is neuroprotective. In this study, we investigated the effect of pinealectomy and administration of exogenous melatonin on oxidative stress and morphological changes after experimental brain injury.

Microanatomical architecture of dorello's canal and its clinical implications

OBJECTIVE We investigated the membranous architecture of the abducens nerve at the petroclival region and describe the characteristics of this area in cadaveric specimen and two children with hydrocephalus and sixth nerve palsy using magnetic resonance imaging (MRI). MATERIALS AND METHODS Five adult cadaver heads were used to investigate the petroclival part of the abducens nerve. The heads were injected with colored latex for microsurgical dissection, and the length of the dural sleeve of the abducens nerve and its width at the apex were measured. In one cadaver head, the area between the petroclival entrance porus of the abducens nerve and the cavernous sinus was histologically studied under light microscopy. In two patients with hydrocephalus and abducens nerve palsy, the petroclival area was screened by using the MRI fat suppression technique. RESULTS In the cadavers, the arachnoid membrane on the clivus extended within the dural sleeve as far as the petrous apex, as an extension of the subarachnoid space. The average length of the dural sleeve was 9.5 mm and the average width was 1.5 mm at the apex, where the nerve entered the cavernous sinus. MRI scans showed that the cerebrospinal fluid distance of the petroclival region was 5 mm in the first patient and 7 mm in the second. CONCLUSION The subarachnoid space inside the dural sleeve of the abducens nerve can be defined by using thin-slice MRI scans. Enlargement of the dural sleeve at the petroclival region may coexist with the abducens nerve palsy. It has been documented in this study that the arachnoid membrane forms a membraneous barrier between the subarachnoid and subdural spaces within Dorellos canal.

Melatonin as a free radical scavenger in experimental head trauma

Head trauma causes two kinds of injury in the neural tissue. One is the primary injury which occurs at the time of impact. The other one is a secondary injury and is a progressive process. Free radicals are produced during oxidative reactions formed after trauma. They have been thought to be responsible in the mechanism of the secondary injury. Some studies have been conducted to demonstrate the role of free oxygen radicals in neuronal injury. The alterations in the free radical level during the early posttraumatic period and the effect of a free radical scavenger on these alterations have not been studied as a whole. We aimed to demonstrate the free oxygen radical level changes in the early posttraumatic period and the effect of melatonin, which is a potent free radical scavenger, on the early posttraumatic free radical level. A two-staged experimental head trauma study was designed. In stage one, posttraumatic free radical level changes were determined. In the second stage, the effect of melatonin on the free radical level changes in the posttraumatic period was studied. Two main groups of rats each divided into four subgroups were studied. Rats in one of the main groups underwent severe head trauma, and malondealdehyde (MDA) levels were measured in the contused cerebral tissue at different time points. Rats in the other main group also underwent the same type of trauma, and melatonin was injected intraperitoneally at different time points after trauma. The MDA level alteration in the tissue was determined after the injection of melatonin. The MDA level increased rapidly in the early posttraumatic period. But in time, it decreased in the groups with only trauma. In the melatonin-treated group, the MDA level decreased after the injection of melatonin, when injected in the early posttraumatic period, compared to the control and trauma groups. However, melatonin increased MDA to a higher level than in the groups with only trauma and the control group when injected later than 2 h after trauma. The MDA level increases in the very early posttraumatic period of cerebral trauma and decreases in time. Melatonin, which is the most potent endogenous free radical scavenger, when injected intraperitoneally to the cerebral traumatized rats in the very early posttraumatic period, causes a significant decrease in the MDA level. But, melatonin, when injected more than 2 h after trauma, increases the MDA level in experimental cerebral trauma in rats.

Post-traumatic early epilepsy in pediatric age group with emphasis on influential factors

ObjectivePosttraumatic epilepsy in the pediatric age group is mostly seen within the first week. An acute posttraumatic epileptic fit, which may induce secondary insults, should be hindered. The aim of the study is to define the risk factors for posttraumatic early epilepsy (PTEE) and the indications for prophylactic therapy.MethodsIn this survey, a total of 1,785 pediatric patients—under the age of 16—are studied. The majority of the patients (1,655) were treated in Haydarpaşa Numune Hospital within the years 1993–1999. The rest, which consists of 130 patients, were treated in Inönü University Turgut Özal Medical Center between the years 2001 and 2003. The patients were categorized according to age, gender, neurological manifestations, type of trauma, cranial pathology, number and type of epileptic fits, the interval between trauma and convulsion, electroencephalogram findings, and antiepileptic therapy. All these factors were challenged due to their effect on the evolution of PTEE.ResultsOnly 149 cases had PTEE (8.4%). There was no correlation between gender and the incidence of PTEE. The data showed that 11.7% of the patients at or under the age of 3 (p=0.00072), 30.8% of the patients with severe head injury (Glasgow Coma Scale=3–8; Children’s Coma Scale = 3–8; p=0.00000), 19.3% of the patients with depressed skull fractures (p=0.00038), 13.7% of the patients with intraparenchymal hemorrhage (p=0.0000072), and 21.6% of the patients with cerebral edema (p=0.000008) had PTEE. Only 20% of the patients with PTEE had a Glasgow Outcome Scale (GOS) of 3 or less (p=0.0000075).ConclusionThose patients at or under the age of 3, with severe head injury, cerebral edema, intraparenchymal hemorrhage, or depressed skull fracture, have a higher incidence of PTEE. Moreover, because the GOS of these patients are prone to be worse, antiepileptic therapy in acute stage may be effective in preventing the secondary brain damage.