Ismail Akdemir

Melatonin reduces glial reactivity in the hippocampus, cortex, and cerebellum of streptozotocin-induced diabetic rats

Hyperglycemia plays a critical role in the development and progression of diabetic neuropathy. One of the mechanisms by which hyperglycemia causes neural degeneration is via the increased oxidative stress that accompanies diabetes. Metabolic and oxidative insults often cause rapid changes in glial cells. Key indicators of this response are increased synthesis of glial fibrillary acidic protein (GFAP) and S100B, both astrocytic markers. In the present study, we examined glial reactivity in hippocampus, cortex, and cerebellum of streptozotocin (STZ)-induced diabetic rats by determining the expression of GFAP and S-100B and we evaluated the effect of melatonin on the glial response. Western blot measurement of contents in brain regions after 6 weeks of STZ-induced diabetes indicated significant increases in these constituents compared with those in nondiabetic controls. Administration of melatonin prevented the upregulation of GFAP in all brain regions of diabetic rats. Using GFAP immunohistochemistry, we observed an increase in GFAP immunostaining in the hippocampus of STZ-diabetic rats relative to levels in the control brains. Treatment with melatonin resulted in an obvious reduction of GFAP-immunoreactive astrocytes in hippocampus. Like GFAP, S100B levels also were increased in all three brain areas of diabetic rats, an effect also reduced by melatonin treatment. Finally, the levels of lipid peroxidation products were elevated as a consequence of diabetes, with this change also being prevented by melatonin. These results suggest that diabetes causes increased glial reactivity possibly due to elevated oxidative stress, and administration of melatonin represents an achievable adjunct therapy for preventing gliosis.

Learning and memory deficits in rats induced by chronic thinner exposure are reversed by melatonin.

Abstract:  Thinner is a neurotoxic mixture which is widely used as an aromatic industrial solvent. This product has been shown to cause functional and structural changes in the central nervous system. We investigated the effect of exposure to high concentrations (3000 p.p.m.) of thinner for 45 days (1 hr/day) on cognitive functions and the levels of neural cell adhesion molecules (NCAM) and lipid peroxidation products (LPO) in the hippocampus, cortex and cerebellum of rats. The actions of melatonin on the effects produced by thinner exposure were also tested. Thinner exposure caused a significant increase in LPO (malondialdehyde and 4‐hydroxyalkenals) in all brain regions. Melatonin administration significantly reduced LPO and elevated glutathione levels in the brain regions. NCAM (180 kDa) was significantly decreased in hippocampus and cortex of thinner‐exposed rats. Furthermore, thinner‐exposed rats showed cognitive deficits in passive avoidance and Morris water maze tasks, whereas in the rats chronically treated with melatonin these effects were reversed. This study indicates that treatment with melatonin prevents learning and memory deficits caused by thinner exposure possibly by reducing oxidative stress and regulating neural plasticity.

Duplication of the abducens nerve at the petroclival region. An anatomic study

OBJECTIVEDuring its course between the brainstem and the lateral rectus muscle, the abducens nerve usually travels forward as a single trunk, but it is not uncommon for the nerve to split into two branches. The objective of this study was to establish the incidence and the clinical importance of the duplication of the nerve. METHODSThe study was performed on 100 sides of 50 autopsy materials. In 10 of 11 cases of duplicated abducens nerve, colored latex was injected into the common carotid arteries and the internal jugular veins. The remaining case was used for histological examination. RESULTSFour of 50 cases had duplicated abducens nerve bilaterally. In seven cases, the duplicated abducens nerve was unilateral. In 9 of these 15 specimens, the abducens nerve emerged from the brainstem as a single trunk, entered the subarachnoid space, split into two branches, merged again in the cavernous sinus, and innervated the lateral rectus muscle as a single trunk. In six specimens, conversely, the abducens nerve exited the pontomedullary sulcus as two separate radices but joined in the cavernous sinus to innervate the lateral rectus muscle. In 13 specimens, both branches of the nerve passed beneath the petrosphenoidal ligament. In two specimens, one of the branches passed under the ligament and the other passed over it. In one of these last two specimens, one branch passed over the petrosphenoidal ligament and the other through a bony canal formed by the petrous apex and the superolateral border of the clivus. In all of the specimens, both branches were wrapped by two layers: an inner layer made up of the arachnoid membrane and an outer layer composed of the dura during its course between their dural openings and the lateral wall of the cavernous segment of the internal carotid artery. This finding was also confirmed by histological examination in one specimen. CONCLUSIONDouble abducens nerve is not a rare variation. Keeping such variations in mind could spare us from injuring the VIth cranial nerve during cranial base operations and transvenous endovascular interventions.

Effects of Prostaglandin E1, Melatonin, and Oxytetracycline on Lipid Peroxidation, Antioxidant Defense System, Paraoxonase (PON1) Activities, and Homocysteine Levels in an Animal Model of Spinal Cord Injury

Study Design. Investigation of the effects of prostaglandin E1, melatonin, and oxytetracycline on lipid peroxidation, antioxidant and paraoxonase activities, and homocysteine levels in an experimental model of spinal cord injury. Objectives. To determine the antioxidant efficacy of prostaglandin E1, melatonin, and oxytetracycline and whether paraoxonase and homocysteine can be used as monitoring parameters in the acute oxidative stress of spinal cord injury. Summary of Background Data. Melatonin has been found useful in spinal cord injury in previous studies. No study exists investigating the effects of melatonin, prostaglandin E1, and oxytetracycline as well as the response type of paraoxonase enzyme and homocysteine levels in the acute oxidative stress of spinal cord injury. Methods. Sixty-three male albino Wistar rats were anesthetized with 400 mg/kg chloral hydrate and divided into 5 groups. The G1 (n = 7) control group provided the baseline levels. G2–G5 underwent T3–T6 total laminectomies and spinal cord injuries by clip compression at the T4–T5 levels. Medications were applied to G3–G5 right after clip compression. Hence, G2 constituted laminectomy + injury, G3 laminectomy + injury + prostaglandin E1; G4 laminectomy + injury + melatonin, and G5 laminectomy + injury + oxytetracycline groups. Animals were decapitated either the first or fourth hour after injury. Spinal cord tissue and blood malonyldialdehyde and plasma homocysteine levels, plasma glutathione peroxidase, superoxide dismutase, paraoxonase activities were assayed. The SPSS 9.0 program was used for statistical analysis and graphics. Intergroup comparisons were made by Bonferroni corrected Mann Whitney U test (P < 0.025) and intragroups comparisons by Wilcoxon Rank test (P < 0.03). Results. In injury groups, plasma homocysteine levels decreased and paraoxonase activities increased as erythrocyte superoxide dismutase levels and plasma glutathione peroxidase activities decreased in parallel to increases of tissue and blood malonyldialdehyde levels. These alterations were relatively suppressed by prostaglandin E1, melatonin, and oxytetracycline administrations in varying degrees. Melatonin was the most powerful agent, particularly at the fourth hour. Oxytetracycline was also effective, both at the first and fourth hour. Prostaglandin E1 was effective in comparison to injury group, but not as much as melatonin and oxytetracycline. Conclusions. Melatonin and oxytetracycline are effective in preventing lipid peroxidation in spinal cord injury. Paraoxonase and homocysteine can be used in monitoring the antioxidant defense system as well as superoxide dismutase and plasma glutathione peroxidase, both in injury and medicated groups.

Medroxyprogesterone acetate, enoxaparin and pentoxyfylline cause alterations in lipid peroxidation, paraoxonase (PON1) activities and homocysteine levels in the acute oxidative stress in an experimental model of spinal cord injury.

Summary. Background: Effects of medroxyprogesterone acetate, enoxaparin and pentoxyfylline on lipid peroxidation, antioxidant defence system, paraoxonase activities, and homocysteine levels in an experimental model of spinal cord injury were investigated. Method: Sixty-three male albino Wistar rats were anaesthetized by 400 mg/kg chloral hydrate and divided into 5 groups. G1 (n 7) = control group provided the baseline levels. G2–G5 underwent T3–6 total laminectomies and spinal cord injuries by clip compression at T4–5 levels. Medications were applied to G3–G5 right after the injury. Hence, G2 constituted laminectomy + injury (lam+I); G3 = lam + I + medroxyprogesterone acetate (MPA), G4 = lam + I + enoxaparin (E), and G5 = lam+I+pentoxyfylline (P) groups. Animals were decapitated either at the 1st or 4th hour after injury. Tissue and blood malonyldialdehyde (MDA) and plasma homocysteine and erythrocyte superoxide dismutase (SOD) levels, and erythrocyte glutathione peroxidase (GSH-Px) and plasma paraoxonase (PON1) activities were assayed. SPSS 9.0 program was used for statistical analysis and graphics. Intergroup comparisons were made by Bonferroni corrected Mann Whitney U test (P<0.025), and intragroups comparisons by Wilcoxon Rank test (P<0.03). Findings: In intergroup comparison, G1–G2, G1–G3, G1–G5, G2–G3, G2–G4, and G4–5 groups differed from each other for all parameters (P<0.025, MWU) except for G4–G5 4th hour MDA levels. G1–G4 was similar for all 1st hour parameters (P>0.025, MWU), but different for 4th hour (P<0.025, MWU) except for GSH-Px and SOD levels. For G2–G5, all parameters for 1st and 4th hour were similar except for 4th PON1, Hcy and SOD levels. For G3–G4, all 1st hour parameters were different from each other (P<0.025, MWU); whereas all 4th hour parameters were similar except for SOD level. For G3–G5, all parameters at 1st and 4th hour were similar except for 4th hour GSH-Px, PON1, and Hcy. In intragroup comparison, all parameters differed from each other at all times (P<0.03, WRT) except for 1st hour G4 MDA, Hcy and SOD levels compared to basal levels. Interpretation: In injury groups, plasma Hcy levels decreased and PON1 activities increased as erythrocyte SOD level and GSH-Px activities decreased in parallel to increases of tissue and blood MDA levels. These changes were relatively suppressed by MPA, enoxaparin and pentoxyfylline administrations at varying degrees. Enoxaparin was the most powerful agent, particularly at 1st hour. MPA was also effective, particularly at 4th hour. Pentoxyfylline despite having slight effect at 4th hour, was not effective according to both control and injury groups. Enoxaparin and MPA can be used in the treatment of spinal cord injuries. PON1 and Hcy are helpful in monitoring the antioxidant defence system as well as SOD and GSH-Px, both in injury and medically treated groups.

The significance of the percentage of the defect size in spina bifida cystica in determination of the surgical technique.

Abstract Aim. Our aim was to classify meningoceles and meningomyeloceles in terms of defect area as a percentage of the thoracolumbar region to make it possible to select the surgical technique accordingly. Materials and methods. Thirty-two cases were included in the study program. Any defect smaller than 8% of the thoracolumbar region was primarily sutured and classed as grade 1. Results. The defects that it was not possible to handle with primary suture because of the broad base and thereby closed with muscle–skin flaps were those occupying more than 8% of the thoracolumbar region and these were classed as grade 2. It was not possible to perform primary repair of any defect occupying more than 8% of the thoracolumbar area. Conclusion. The use of combined latissimus dorsi+gluteus maximus muscle–skin flaps was found to be safe in broad-based meningomyelocele defects, as they provide wider closures and permanent bolstering of the meningomyelocele defect, thus protecting the region against multiple trauma.

Asymptomatic interval in delayed traumatic intracerebral hemorrhage: report of two cases

Delayed traumatic intracranial hemorrhage (DTICH) is seen mostly in trauma to the occipitoparietal region by countercoup mechanism. It is most encountered within the first posttraumatic 10 days, particularly in the first 3. Herein, two cases of delayed traumatic intracerebral hemorrhage were discussed, first one presented with headache and vomiting who had been asymptomatic for 168 days after head trauma and the other presented with dysarthria and hyperkynesias after 92 days of asymptomatic interval, either being longer than that of the previous cases reported in the literature. Despite a long time elapse, DTICH should be considered in the differential diagnosis in the patients with history of head trauma that manifests at later stages with intracranial pressure elevation symptoms such as headache, vomiting.