Razi Journal of Medical Sciences

fa اثر حفاظتی تمرینات مقاومتی و ویتامین D بر تغییرات هیستوپاتولوژی بافت نخاع در رت‌های ماده مبتلا به آنسفالومیلیت خود ایمن تجربی The Protective Effect of Resistance Training and Vitamin D on the Histopathological Changes of Spinal Cord Tissue in Female Rats with Experimental Autoimmune Encephalomyelitis فیزیولوژی ورزش Exercise Physiology پژوهشي Research <div style="text-align: justify;">زمینه و هدف: آسیبشناسی طناب نخاعی یک عامل تعیین کننده اصلی ناتوانی غیرقابل برگشت در مولتیپل اسکلروزیس پیشرونده است. هدف از این مطالعه بررسی اثر حفاظتی تمرینات مقاومتی و ویتامین D بر تغییرات هیستوپاتولوژی بافت نخاع در رت های ماده مبتلا به آنسفالومیلیت خود ایمن تجربی بود. روش کار: در این پژوهش تجربی، 48 سر موش ماده نژاد لوئیز 4 هفتهای بهطور تصادفی به 8 گروه کنترل سالم، کنترل MS، ویتامین D سالم، ویتامین D+MS، تمرین مقاومتی سالم، تمرین مقاومتی+MS، ویتامین D+مقاومتی سالم، MS+تمرین مقاومتی+ویتامینD تقسیم شدند. رتها با نخاع خوکچه هندی و ادجوانت کامل ایمونیزه شدند. مدل EAE در انتهای هفته ششم تمرینات القاء شد. رتها به ازای هر کیلوگرم وزن بدن 5میکروگرم ویتامین  D3در 150 میکرولیتر روغن کنجد هر دو روز یک بار به مدت 2 هفته بهصورت داخل صفاقی دریافت کردند. پروتکل تمرین مقاومتی به مدت 6 هفته و 5 روز در هفته انجام شد. مقاطع میکروسکوپی انتخابشده بافت نخاع، پس از رنگآمیزی هماتوکسیلین و آئوزین با میکروسکوپ نوری مطالعه شدند. یافته‌ها: یافتههای هیستوپاتولوژی بافت نخاع نشان داد گروههای کنترل سالم، D کنترل سالم و D مقاومتی سالم دارای بافت نخاع کاملا طبیعی بودند. در گروه کنترل MS علاوهبر تخریب شدید میلین، التهاب مشاهده شد. در گروههای تمرین مقاومتی سالم و مقاومتی MS پرخونی عروق مشاهده شد. در گروه D کنترل MS التهاب و تخریب میلین مشاهده شد و در گروه D مقاومتی MS التهاب و تخریب میلین بهصورت جزیی وجود داشت. نتیجه گیری: بهنظر میرسد تمرینات مقاومتی به همراه مصرف ویتامین D میتواند از تخریب میلین و التهاب بافت نخاع جلوگیری کند. </div> <div style="text-align: justify;">Background & Aims: Multiple sclerosis is defined as a chronic inflammatory disease of the central nervous system that results in large focal lesions in the white matter of the brain and spinal cord, characterized by primary demyelination of variable axonal extent (1-4). Recently, the spinal cord tissue has received a lot of attention, so that the disorder in the spinal cord tissue leads to the disability of the affected patients (5-7). Spinal cord pathology is a major determinant of irreversible disability in progressive multiple sclerosis. Demyelinated lesion is the main characteristic of multiple sclerosis pathology (8-10). Considering the defined anatomy of the spinal cord, the study of the topography of the lesion may provide important clues about the pathogenesis of the disease. Therefore, examination of the spinal cord tissue and its possible histopathology results can be useful. There is a need for better use of existing treatments and the need for new alternative treatment options to stop the progression of multiple sclerosis and improve the mechanisms (12). In this regard, vitamin D is known as an important immunomodulatory factor, and as a result, poor vitamin D status is associated with a large number of diseases, including multiple sclerosis (14-16). On the other hand, today it is known that exercise is beneficial for the whole body and even the brain. Exercise increases the blood flow in the whole body and of course the blood flow in the brain increases as well. Studies conducted on humans and animals show that exercise increases brain function (including increasing synaptic plasticity and increasing learning and memory) and helps to recover from neurological diseases (20). In animal models of multiple sclerosis, it has been shown that exercise improves spinal cord demyelination, reduces the permeability of the blood brain barrier, and reduces the infiltration of leukocytes (21). So far, research has not investigated the effect of exercise along with vitamin D supplementation on brain tissue structure in MS. Aerobic exercises can improve the walking speed and balance of people with MS (22, 23) and are very effective in reducing the fatigue of these patients (24). However, patients with MS may not be able to use endurance exercises due to severe weakness; because they cannot perform endurance exercises with intensity and in sufficient time. Therefore, a period of resistance training can be more effective than endurance training. Resistance exercises can improve motor performance and muscle strength in patients with MS. Also, performing resistance training causes movement units to be called and increase the frequency of electric discharge of motor neurons, following these changes, the amount of fatigue decreases and the energy to perform the activity increases. In addition, the beneficial effects of resistance training on the nervous system have been reported (25). The strategy of preventive effects of regular resistance exercises along with vitamin D consumption with the aim of synergizing these two factors in dealing with MS disease is a new perspective, whose effects on the histopathology of the spinal cord tissue in the experimental autoimmune encephalomyelitis model have not been investigated so far. Therefore, in the present study, the researcher intends to evaluate the protective effect of Resistance Training and Vitamin D on the histopathological changes of spinal cord tissue in Female Rats with Experimental Autoimmune Encephalomyelitis. Methods: In this experimental study, In this experimental research, 48 male Louise 4-week-old female rats were randomly divided into 8 groups: healthy control, MS control, healthy vitamin D, vitamin D+MS, healthy resistance training, resistance training+MS, vitamin D+healthy resistance, MS+resistance training+vitamin D. The rats were immunized with the guinea pig's spit and complete adjuvant. The EAE model was induced at the end of the sixth week of exercise. Rats received 5 μg of body weight per kilogram of vitamin D3 in 150 μl of sesame oil every two days once for 2 weeks’ intraperitoneal injection. Resistance training protocol was performed for 6 weeks and 5 days a week. Starting a training program with a load equal to 50% of the body weight of the rat. Animals in the first two sessions performed 8 to 10 repetitions (climbing the ladder) at 2-minute breaks. Selected microscopic sections of spinal cord tissue, then stained with hematoxylin and eosin were studied with optical microscope. Results: Histopathological findings of the spinal cord showed that healthy control, D healthy control and healthy D resistance group were spinal cord tissue completely normal. In the MS control group, in addition to severe myelin degradation, inflammation was observed. In the healthy resistance training and MS resistance groups was observed vascular Hyperemia. In the D MS control group was found inflammation and myelin degradation, and in the D MS resistance group, inflammation and myelin degradation were partially. Conclusion: The histopathology results of the spinal cord tissue in the present study showed that severe myelin destruction and inflammatory cells were observed in the MS control groups. In addition to the destruction of the spinal cord, the size of the spinal cord has increased and there is also an accumulation of inflammatory cells. In the healthy and multiple sclerosis resistance training groups, vascular hyperemia was observed, but there was no myelin destruction and inflammation. These findings are consistent with the results of previous studies that have shown that multiple sclerosis is associated with the destruction of myelin and inflammatory cells in the spinal cord tissue (8-10). Consistent with the results of the present study, Luzinski et al. (2021) reported that exercise in animal models of multiple sclerosis improves spinal cord demyelination and inflammation (21). In animal studies, the results of exercise in healthy mice or modeling neurological conditions include reduced neuroinflammation or breakdown of the blood-brain barrier, neurogenesis, oligodendrogenesis, neuroprotection, and remyelination. The mechanisms by which exercise improves CNS health appear to be brain-derived neurotrophic factor production, reduction of pro-inflammatory responses, and modulation of microglia activity (29-32). Also, the histopathology findings of the spinal cord tissue showed that inflammation and myelin destruction were observed in the vitamin D control experimental autoimmune encephalomyelitis group, however, myelin destruction was less than the experimental autoimmune encephalomyelitis group. Therefore, vitamin D3 consumption has an effect on the histopathology of the spinal cord tissue of female rats suffering from experimental autoimmune encephalomyelitis (EAE). According to the results, vitamin D3 consumption can prevent myelin destruction and inflammation of the spinal cord tissue. Vitamin D can help regulate immunity and inflammation in multiple sclerosis (14, 15). Since the spinal cord tissue of the multiple sclerosis vitamin D group had less myelin destruction than the multiple sclerosis control group, it can be concluded that vitamin D had a positive protective role in preventing EAE complications. On the other hand, in the present research, the findings of the histopathology of the spinal cord tissue showed that in the combined group of resistance training with vitamin D consumption in the MS group, inflammation and myelin destruction were present in a small way, in fact, the myelin destruction was less compared to multiple sclerosis. Therefore, according to the results of resistance training and vitamin D consumption alone, the combination of resistance training and vitamin D consumption can prevent the destruction of myelin and inflammation of the spinal cord tissue. There were some limitations in the present research, including the lack of measurement of functional indicators of spinal cord tissue. Also, by changing the dose of vitamin D, clearer results may be achieved. However, more research is needed in this field. According to the results, it seems that resistance exercises along with vitamin D intake can prevent myelin destruction and inflammation of spinal cord tissue. Since there was less myelin destruction in the spinal cord tissue following resistance training and vitamin D consumption than in the MS group, it can be concluded that resistance training and vitamin D consumption had a positive protective role in preventing EAE complications. </div> تمرین مقاومتی, ویتامین D, بافت نخاع, مولتیپل اسکلروزیس Resistance Training, Vitamin D, Spinal Cord Tissue, Multiple Sclerosis 1 11 http://rjms.iums.ac.ir/browse.php?a_code=A-10-7165-2&slc_lang=fa&sid=1 Smatalsadat Mousavi عصمت السادات موسوی 3900319475328460090442 0009-0004-8452-2742 No PhD in Sports Physiology, Farhangian University, Nasibah Campus, Tehran, Iran دکتری فیزیولوژی ورزشی، دانشگاه فرهنگیان، پردیس نسیبه، تهران، ایران Zia Falahmohammadi ضیاء فلاح محمدی mousavi2753@gmail.com 3900319475328460090443 3900319475328460090443 Yes Associate Professor, Department of Exercise Physiology, Faculty of Sport Sciences, University of Mazandaran, Babolsar, Mazandaran, Iran دانشیار، گروه فیزیولوژی ورزش، دانشکده علوم ورزشی، دانشگاه مازندران، بابلسر، ایران Farideh Feizi فریده فیضی 3900319475328460090444 3900319475328460090444 No Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran مرکز تحقیقات زیست شناسی سلولی و مولکولی، پژوهشکده بهداشت، دانشگاه علوم پزشکی بابل، بابل، ایران