Faik Ozveren

Melatonin protects the central nervous system of rats against toluene-containing thinner intoxication by reducing reactive gliosis

Neuroprotective effects of melatonin against free radical damage have been studied extensively. Thinner containing 60-70% toluene 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. Toluene generates reactive oxygen species (ROS) and the toxic effects relating to these reactants. In the present study we investigated glial reactivity in hippocampus, cortex and cerebellum and the expression of glial fibrillary acidic protein (GFAP) after exposure of rats to toluene vapor (3000 ppm) for 45 days. We also examined the protective effects of melatonin against gliosis. Western blots demonstrated a marked elevation in total GFAP, a specific marker for astrocytes, by thinner fume inhalation in the hippocampus (P<0.001), cortex (P<0.01) and cerebellum (P<0.05) of rats. Melatonin administration prevented the increase of total GFAP induced by thinner fume inhalation. Thinner exposure caused a significant increase of lipid peroxidation products (malondialdehyde and 4-hydroxyalkenals) in all brain regions (P<0.01 for each region), and this elevation was also was inhibited by melatonin. Furthermore, melatonin augmented glutathione levels in all brain regions (P<0.05 for each region) investigated. In conclusion, melatonin treatment may provide neuroprotection against toluene neurotoxicity by increasing the survival of glial cells possibly by directly scavenging ROS and by indirectly augmenting their antioxidant capacity.

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.

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.

Is indomethacin harmful in spinal cord injury treatment? An experimental study

This study was designed to analyze the effect of early indomethacin on the lipid peroxidation after spinal cord injury in rats. The use of anti-inflammatory drugs to affect delayed and secondary injury after trauma to the spinal cord has now become a matter of standard clinical practice. However, spinal cord injury remains an enormous clinical problem and research that may lead to improved treatment is to be encouraged and commended. Three experimental groups consisting of 40 rats each were formed. Using microsurgical technique, total laminectomy between T5 and T10 was performed. Spinal cord injury was achieved with an epidural aneurysm clip, and pharmacological treatment immediate after the injury was performed by injecting indomethacin intraperitoneally (i.p.) at a dose of 3 mg/kg to indomethacin-treated group. The three main groups were divided into subgroups of 8 rats each. It was planned to stop the biochemical reactions at a different time in each of these subgroups, by the application of liquid nitrogen to the spinal cord and paravertebral structures at the end of the 1st, 15th, 30th, 60th, and 90th minutes. All the spinal cords were removed and protected from further reactions by immersing in the liquid nitrogen tank. The lipid peroxidation levels were assessed by determining thiobarbituric acid reactive substances formation. The results of the study showed that the administration of 3 mg/kg indomethacin immediately after spinal cord injury induces lipid peroxidation to a significant degree (p < 0.05 one-way ANOVA and Tukey HSD tests) when compared to the saline-treated group. This result suggests that early posttraumatic indomethacin treatment may be harmful in spinal cord injury.

Transverse sinus air after cranial trauma.

Air in vascular compartments has been rarely reported. We report a case in whom air within transverse sinus and sinus confluence through ruptured superior sagittal sinus (SSS) due to fractures of parietal and frontal bones was disclosed by computed tomography (CT). Although air in transverse sinus has been reported rarely this could be the first case with air in transverse sinus through the SSS after cranial trauma.