8-hydroxy-2--deoxyguanosine and Brain-Edema

This study aims to determine if erythromycin provides neuroprotective effects against ischemic injury following permanent focal cerebral ischemia.. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO). Each animal received a single subcutaneous injection of erythromycin lactobionate (EM, 50 mg/kg) or vehicle immediately after ischemia. The infarct volume, edema index and neurological performance were evaluated at 24 and 72 h after MCAO. The cerebral blood flow (CBF) was measured with an MRI system at 30 min after MCAO. TUNEL staining and immunohistochemical analyses for oxidative stress (4-HNE, 8-OHdG) and inflammation (Iba-1, TNF-α) in the cortex were conducted at 24 and 72 h after MCAO.. The CBF did not differ between the EM-treated and vehicle-treated groups. The EM treatment significantly reduced the infarct volume (p < 0.01) at 24 and 72 h after MCAO and significantly reduced the edema index (p < 0.01) at 24 h. The EM treatment significantly improved the neurological deficit scores (p < 0.05) at 24 and 72 h. EM also significantly suppressed the accumulation of 4-HNE (p < 0.01) and 8-OHdG (p < 0.01) and markedly reduced Iba-1 (p < 0.01) and TNF-α expression (p < 0.05) at both time points. The EM treatment significantly reduced TUNEL-positive cells (p < 0.01) at both time points.. These findings suggest that EM can protect against the neuronal damage caused by cerebral ischemia by alleviating inflammation and reducing oxidant stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aldehydes; Animals; Blood Pressure; Body Temperature; Brain Edema; Brain Infarction; Brain Injuries; Calcium-Binding Proteins; Cerebrovascular Circulation; Deoxyguanosine; Disease Models, Animal; Erythromycin; In Situ Nick-End Labeling; Infarction, Middle Cerebral Artery; Magnetic Resonance Imaging; Microfilament Proteins; Neuroprotective Agents; Rats; Statistics, Nonparametric; Time Factors; Tumor Necrosis Factor-alpha

A previous study in our laboratory showed the neuroprotective effects of COA-Cl, a novel synthesized adenosine analog, in a rat cerebral ischemia model. The purpose of the present study was to evaluate the neuroprotective effects of COA-Cl in intracerebral hemorrhage (ICH), another common type of stroke, and investigate potential mechanisms of action.. Adult Sprague-Dawley rats received an injection of 100 µl autologous whole blood into the right basal ganglia. COA-Cl (30 µg/kg) was injected intracerebroventricularly 10 minutes after ICH. A battery of motor deficit tests were performed at 1 day, 3 days, 5 days, and 7 days after ICH. To investigate the mechanism of action, brain water content, TUNEL staining and 8-OHdG immunostaining, and ELISA (to assess oxidative stress) were used.. COA-Cl treatment significantly attenuated sensorimotor deficits and reduced brain edema 1 day after ICH. Furthermore, the numbers of perihematomal TUNEL- and 8-OHdG-positive cells were significantly decreased in COA-Cl treated ICH rats.. These results indicate that COA-Cl has neuroprotective effects in ICH. Furthermore, our study provides evidence that COA-Cl may reduce oxidative stress, which may be one mechanism underlying its neuroprotective effects.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adenosine; Animals; Antioxidants; Apoptosis; Behavior, Animal; Biomarkers; Body Water; Brain; Brain Edema; Cerebral Hemorrhage; Deoxyguanosine; Disease Models, Animal; Injections, Intraventricular; Male; Motor Activity; Neuroprotective Agents; Oxidative Stress; Rats, Sprague-Dawley; Time Factors

In recent studies, molecular hydrogen selectively reduced the levels of hydroxyl radicals in vitro and exerted a therapeutic anti-oxidant activity in a rat middle cerebral artery occlusion model. The aim of this study was to investigate the effect of hydrogen gas on a mouse bilateral common carotid artery occlusion (BCCAO) model. Male C57BL/6J mice were subjected to transient BCCAO with a nontraumatic aneurysm clip. The mice were divided into three groups: sham, BCCAO, and BCCAO treated with 1.3 % hydrogen gas. Cerebral blood flow (CBF) in the cortex was measured sequentially for both hemispheres with a non--invasive and noncontact laser Doppler blood perfusion imager during the procedure. Vital signs were also recorded. Oxidative stress evaluated by measuring the level of 8-hydroxy-2'-deoxyguanosine (8-OHdG), neuronal injury in the hippocampal CA1 sector, and brain water content were assessed 24 h after ischemia. The hydrogen gas treatment had no significant effect on vital signs or CBF values. However, the reduction of the expression of 8-OHdG, the decrease in the neuronal injury in the hippocampal CA1 sector, and the attenuation in brain water content were observed in hydrogen-treated mice. In conclusion, hydrogen gas might be effective in a mouse BCCAO model.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Analysis of Variance; Animals; Arterial Occlusive Diseases; Brain Edema; Carotid Artery, Common; Cerebrovascular Circulation; Deoxyguanosine; Disease Models, Animal; Hippocampus; Hydrogen; Laser-Doppler Flowmetry; Male; Mice; Mice, Inbred C57BL; Reperfusion; Ultrasonography

To elucidate the pathogenic roles of oxidative stress on blood-brain-barrier (BBB) dysfunction, we compared the chronological changes of oxidative stress in blood and cerebral tissue between stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). Plasma and tissue oxidative stress was assayed by the diacron-reactive oxygen metabolite (d-ROM) test using 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a reference oxidative stress marker. The plasma and cerebral cortex d-ROM levels increased in SHRSP after 16weeks of age, but not in WKY. There were no significant differences in 8-OHdG or lipid peroxidation markers between SHRSP and WKY. Antioxidant capacity, as estimated by the biological antioxidant potential test, was similar between SHRSP and WKY at all ages examined. The changes in plasma and tissue d-ROM levels coincided with changes in glucose transporter-1 and aquaporin-4 expression, as functional constituents of the BBB. These results indicate that plasma oxidative stress increases before the onset of tissue damage, and plays an important role in BBB dysfunction rather than decreases in antioxidant capacity. The plasma d-ROM test appears to be useful for predicting vasogenic cerebral edema in severe hypertension.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Aquaporin 4; Biomarkers; Blood Pressure; Blood-Brain Barrier; Body Weight; Brain Edema; Capillary Permeability; Deoxyguanosine; Disease Models, Animal; Glucose Transporter Type 1; Hypertension; Lipid Peroxidation; Male; Oxidative Stress; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Stroke; Time Factors

Our previous study indicated that consuming (-)-epigallocatechin gallate (EGCG) before or after traumatic brain injury (TBI) eliminated free radical generation in rats, resulting in inhibition of neuronal degeneration and apoptotic death, and improvement of cognitive impairment. Here we investigated the effects of administering EGCG at various times pre- and post-TBI on cerebral function and morphology. Wistar rats were divided into five groups and were allowed access to (1) normal drinking water, (2) EGCG pre-TBI, (3) EGCG pre- and post-TBI, (4) EGCG post-TBI, and (5) sham-operated group with access to normal drinking water. TBI was induced with a pneumatic controlled injury device at 10 weeks of age. Immunohistochemistry and lipid peroxidation studies revealed that at 1, 3, and 7 days post-TBI, the number of 8-Hydroxy-2'-deoxyguanosine-, 4-Hydroxy-2-nonenal- and single-stranded DNA (ssDNA)-positive cells, and levels of malondialdehyde around the damaged area were significantly decreased in all EGCG treatment groups compared with the water group (P < 0.05). Although there was a significant increase in the number of surviving neurons after TBI in each EGCG treatment group compared with the water group (P < 0.05), significant improvement of cognitive impairment after TBI was only observed in the groups with continuous and post-TBI access to EGCG (P < 0.05). These results indicate that EGCG inhibits free radical-induced neuronal degeneration and apoptotic death around the area damaged by TBI. Importantly, continuous and post-TBI access to EGCG improved cerebral function following TBI. In summary, consumption of green tea may be an effective therapy for TBI patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aldehydes; Animals; Brain Edema; Brain Injuries; Catechin; Deoxyguanosine; Disease Models, Animal; DNA, Single-Stranded; Drug Administration Schedule; Glial Fibrillary Acidic Protein; Lipid Peroxidation; Male; Maze Learning; Neurons; Neuroprotective Agents; Phosphopyruvate Hydratase; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Wistar; Time Factors

Paraquat (PQ) is a common herbicide and PQ poisoning is a major medical problem in Asia. However, few studies have focused on the acute neurotoxic changes caused by PQ. Here we report the acute neurotoxicological findings of rats treated with lethal dose of PQ. In substantia nigra (SN) and striatum we found obvious microglia (labeled by Iba-1) activation within one week. In SN and hippocampus, we detected increased oxidative stress in the neurons based on NeuN/8-OHdG immunofluorescence double labeling and laser cofocal microscopy. Moreover, we provided ultrastructural evidences of astrocyte edema and neurons apoptosis in rat brain by electron microscopy. Further studies will be needed with non-lethal dose of PQ to confirm these results and demonstrate the direct CNS toxicity of PQ.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antigens, Nuclear; Apoptosis; Astrocytes; Biomarkers; Brain; Brain Edema; Deoxyguanosine; Disease Models, Animal; Fluorescent Antibody Technique; Herbicides; Lipid Peroxidation; Microglia; Microscopy, Confocal; Microscopy, Electron, Transmission; Nerve Tissue Proteins; Neurons; Neurotoxicity Syndromes; Oxidative Stress; Paraquat; Rats; Rats, Sprague-Dawley; Time Factors

Our previous studies have demonstrated that thrombin plays an important role in intracerebral hemorrhage (ICH)-induced brain injury and edema formation. We, therefore, examined whether nafamostat mesilate (FUT), a serine protease inhibitor, can reduce ICH-induced brain injury. Anesthetized male Sprague-Dawley rats received an infusion of autologous whole blood (100 microL), thrombin (5U/50 microL) or type VII collagenase (0.4 U/2 microL) into the right basal ganglia, the three ICH models used in the present study. FUT (10 mg/kg) or vehicle was administered intraperitoneally 6 h after ICH (or immediately after thrombin infusion) and then at 12-h intervals (six treatments in total, n = 5 in each group). All rats were sacrificed 72 h later. We also examined whether FUT promotes rebleeding in a model in which ICH was induced by intracerebral injection of collagenase. Systemic administration of FUT starting 6 h after ICH reduced brain water content in the ipsilateral basal ganglia 72 h after ICH compared with vehicle. FUT attenuated ICH-induced changes in 8-OHdG and thrombin-reduced brain edema. FUT did not increase collagenase-induced hematoma volume. FUT attenuates ICH-induced brain edema and DNA injury suggesting that serine protease inhibitor may be potential therapeutic agent for ICH.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Basal Ganglia; Benzamidines; Brain Edema; Brain Injuries; Cerebral Hemorrhage; Collagenases; Deoxyguanosine; Enzyme-Linked Immunosorbent Assay; Functional Laterality; Guanidines; Male; Rats; Rats, Sprague-Dawley; Serine Proteinase Inhibitors; Thrombin