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101.
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We examined the mechanism of 17beta-estradiol (estrogen)-mediated inhibition of apoptosis in C6 (rat glioma) cells following exposure to hydrogen peroxide (H(2)O(2)). Cells were preincubated with 4 microM estrogen for 2 h and then exposed to 100 microM H(2)O(2) for 24 h. Exposure to H(2)O(2) caused significant increases in intracellular calcium (Ca(2+)), as determined by fura-2, which was attenuated by preincubation with estrogen. H(2)O(2) and ionomycin caused cell death in a dose-dependent manner, as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Preincubation with estrogen restored viability in cells exposed to H(2)O(2) but not in cells exposed to ionomycin. Western blot analysis showed an increase in Bax/Bcl-2 ratio, calpain activity, and caspase-3 activity following treatment with H(2)O(2), and estrogen pretreatment decreased levels of all three. Cell morphology, as evaluated by Wright staining, indicated apoptosis in cells treated with H(2)O(2), and pretreatment with estrogen reduced apoptosis. Results from MTT and Wright staining were further supported by the terminal deoxyribonucleotidyl transferase (TdT)-mediated dUTP Nick End Labeling (TUNEL) assay. These results indicate a role for estrogen in preventing apoptosis in C6 glial cells exposed to H(2)O(2). Our results suggest that estrogen may have a protective role in minimizing glial cell apoptosis in neurological diseases such as demyelinating disease or central nervous system trauma. 相似文献
103.
Estrogen attenuated markers of inflammation and decreased lesion volume in acute spinal cord injury in rats 总被引:3,自引:0,他引:3
Sribnick EA Wingrave JM Matzelle DD Wilford GG Ray SK Banik NL 《Journal of neuroscience research》2005,82(2):283-293
Spinal cord injury (SCI) is a devastating neurologic injury with functional deficits for which the only currently recommended pharmacotherapy is high-dose methylprednisolone, which has limited efficacy. Estrogen is a multi-active steroid that has shown antiinflammatory and antioxidant effects, and estrogen may modulate intracellular Ca(2+) and attenuate apoptosis. For this study, male rats were divided into three groups. Sham group animals received a laminectomy at T12. Injured rats received both laminectomy and 40 g x cm force SCI. Estrogen-group rats received 4 mg/kg 17beta-estradiol (estrogen) at 15 min and 24 hr post-injury, and vehicle-group rats received equal volumes of dimethyl sulfoxide (vehicle). Animals were sacrificed at 48 hr post-injury, and 1-cm-long segments of the lesion, rostral penumbra, and caudal penumbra were excised. Inflammation was assessed by examining tissue edema, infiltration of macrophages/microglia, and levels of cytosolic and nuclear NFkappaB and inhibitor of kappa B (IkappaBalpha). Myelin integrity was examined using Luxol fast blue staining. When compared to sham, vehicle-treated animals revealed increased tissue edema, increased infiltration of inflammatory cells, decreased cytosolic levels of NFkappaB and IkappaBalpha, increased levels of nuclear NFkappaB, and increased myelin loss. Treatment of SCI rats with estrogen reduced edema and decreased inflammation and myelin loss in the lesion and penumbral areas, suggesting its potential as a therapeutic agent. Further work needs to be done, however, to elucidate the neuroprotective mechanism of estrogen. 相似文献
104.
Supriti Samantaray Arabinda Das Nakul P. Thakore Denise D. Matzelle Russel J. Reiter Swapan K. Ray Naren L. Banik 《Journal of pineal research》2009,47(2):134-142
Abstract: A vast literature extolling the benefits of melatonin has accumulated during the past four decades. Melatonin was previously considered of importance to seasonal reproduction and circadian rhythmicity. Currently, it appears to be a versatile anti-oxidative and anti-nitrosative agent, a molecule with immunomodulatory actions and profound oncostatic activity, and also to play a role as a potent neuroprotectant. Nowadays, melatonin is sold as a dietary supplement with differential availability as an over-the-counter aid in different countries. There is a widespread agreement that melatonin is nontoxic and safe considering its frequent, long-term usage by humans at both physiological and pharmacological doses with no reported side effects. Endeavors toward a designated drug status for melatonin may be enormously rewarding in clinics for treatment of several forms of neurotrauma where effective pharmacological intervention has not yet been attained. This mini review consolidates the data regarding the efficacy of melatonin as an unique neuroprotective agent in traumatic central nervous system (CNS) injuries. Well-documented actions of melatonin in combating traumatic CNS damage are compiled from various clinical and experimental studies. Research on traumatic brain injury and ischemia/reperfusion are briefly outlined here as they have been recently reviewed elsewhere, whereas the studies on different animal models of the experimental spinal cord injury have been extensively covered in this mini review for the first time. 相似文献
105.
Calpain in the pathophysiology of spinal cord injury: neuroprotection with calpain inhibitors 总被引:10,自引:0,他引:10
Spinal cord injury (SCI) evokes an increase in intracellular free Ca2+ level resulting in activation of calpain, a Ca2+-dependent cysteine protease, which cleaves many cytoskeletal and myelin proteins. Calpain is widely expressed in the central nervous system (CNS) and regulated by calpastatin, an endogenous calpain-specific inhibitor. Calpastatin degraded by overactivation of calpain after SCI may lose its regulatory efficiency. Evidence accumulated over the years indicates that uncontrolled calpain activity mediates the degradation of many cytoskeletal and membrane proteins in the course of neuronal death and contributes to the pathophysiology of SCI. Cleavage of the key cytoskeletal and membrane proteins by calpain is an irreversible process that perturbs the integrity and stability of CNS cells leading to cell death. Calpain in conjunction with caspases, most notably caspase-3, can cause apoptosis of the CNS cells following trauma. Aberrant Ca2+ homeostasis following SCI inevitably activates calpain, which has been shown to play a crucial role in the pathophysiology of SCI. Therefore, calpain appears to be a potential therapeutic target in SCI. Substantial research effort has been focused upon the development of highly specific inhibitors of calpain and caspase-3 for therapeutic applications. Administration of cell permeable and specific inhibitors of calpain and caspase-3 in experimental animal models of SCI has provided significant neuroprotection, raising the hope that humans suffering from SCI may be treated with these inhibitors in the near future. 相似文献
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Hayashi R Iwasaki M Otani T Wang N Miyazaki H Yoshiaki S Aoki S Koyama H Suzuki S 《Journal of epidemiology / Japan Epidemiological Association》2005,15(3):70-77
BACKGROUND: The relative risk of mortality in low and high body mass index (BMI) categories in various ethnic groups remains a controversial subject. METHODS: To examine the relationship between BMI and mortality, a population-based prospective cohort study was conducted in two areas of Gunma Prefecture, Japan, in 1993. A total of 5,554 men and 5,827 women aged 40-69 years completed a self-administered questionnaire and were followed up until the year 2000. The hazard ratios (HRs) were estimated by the Cox proportional hazards model for different BMI classes. RESULTS: During the seven year follow-up period, 329 men and 147 women died. As compared with those in the reference BMI category (22.0-24.9 kg/m(2)), men and women in the lowest BMI category (<18.5 kg/m(2)) had a HR (95% confidence interval [CI]) of death from all-causes of 2.66 (1.59-4.46) and 3.14 (1.38-7.13), respectively, and women in the highest BMI category (28.0+ kg/m(2)) had a HR of death of 3.25 (1.48-7.15), after adjusting for all possible confounding factors including smoking and after excluding deaths occurring during the first three years of follow-up. CONCLUSION: In this prospective study of a Japanese cohort consisting of subjects ranging in age from 40 to 69 years, the curve depicting the relationship between BMI and all-cause mortality was L-shaped in men and U-shaped in women. 相似文献
109.
Elastin stabilization in cardiovascular implants: improved resistance to enzymatic degradation by treatment with tannic acid 总被引:2,自引:0,他引:2
The long-term performance of tissue-derived, glutaraldehyde (Glut)-treated cardiovascular implants such as prosthetic heart valves and vascular grafts is limited by the bio-degeneration of tissue components. While collagen is satisfactorily preserved by Glut, elastin is not stabilized and is highly vulnerable to degradation. The aim of our studies was to develop methods for efficient stabilization of elastin and subsequently reduce its vulnerability towards enzymatic degradation. More specifically, we investigated the use of tannic acid (TA)1 as a novel agent that specifically targets elastin stabilization. Basic investigations on in vitro interactions between Glut, TA and pure aortic elastin provided clear evidence that Glut treatment does not protect elastin from enzymatic degradation. TA bound to elastin in a time-dependent pattern and this binding increased the resistance of elastin to enzymatic degradation. In addition, when TA was used in mixture with Glut, the kinetic of TA binding to elastin was enhanced and this was translated into improved elastin stabilization. Our results clearly documented the superiority of TA as an elastin-stabilizing agent by comparison with the commonly utilized Glut-based tissue crosslinking techniques. 相似文献
110.