دانلود رایگان ترجمه مقاله مسمومیت بر انگیختگی در مدل مزمن مالتیپل اسکلروزیس با حفاظت عصبی کانابینوئید – الزویر 2007
دانلود رایگان مقاله انگلیسی اثرات حفاظت عصبی کانابینوئید در مسمومیت بر انگیختگی در مدل مزمن مالتیپل اسکلروزیس به همراه ترجمه فارسی
عنوان فارسی مقاله: | مسمومیت بر انگیختگی در مدل مزمن مالتیپل اسکلروزیس: اثرات حفاظت عصبی کانابینوئید ها از طریق فعال سازی گیرنده CB1 و CB2 |
عنوان انگلیسی مقاله: | Excitotoxicity in a chronic model of multiple sclerosis: Neuroprotective effects of cannabinoids through CB1 and CB2 receptor activation |
رشته های مرتبط: | پزشکی، مغز و اعصاب |
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توضیحات | ترجمه صفحات پایانی موجود نیست |
نشریه | الزویر (Elsevier) |
کد محصول | F99 |
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جستجوی ترجمه مقالات | جستجوی ترجمه مقالات پزشکی |
بخشی از ترجمه فارسی: التهاب، پاسخ ایمنی، دمیلینه شدن و آسیب آکسونی تصور می شود که نقش مهمی در پاتوژنز مالتیپل اسکلروز (MS) ایفا می کنند. درک و دانش این که آیا آسیب آکسونی عامل یا نتیجه دمینله شدن است یا نه، یک مسئله بسیار مهم است. فرایند های مسمومیت برانگیختگی می توانند عامل آسیب به ماده سفید و آکسون باشند. مطالعات بالینی و آزمایشی نشان می دهند که کانابینوئید ها می توانند در درمان MS کارامد و موثر باشند. با استفاده از مدل مزمن MS در موش، ما در این جا نشان می دهیم که علایم بالینی و آسیب آکسونی در ستون فقرات توسط آنتاگونیست AMPA،NBQX. کاهش یافت. اصلاح علایم شناسی توسط HU210 کانابینویید سنتتیک با کاهش آسیب آکسونی در این مدل همراه بود. به علاوه،HU210 با کاهش آسیب آکسونی در این مدل همراه بود. به علاوه، HU210 موجب کاهش مسمومیت بر انگیختکی ناشی از AMPA هم به صورت درون تنی و هم برون تنی از طریق فعال سازی اجباری هر دو گیرنده کانابینویید CB1 وCB2 می شود. به طور کلی این داده ها بیان گر اهمیت فرایند های مسمومیت برانگیختکی در پاتوژنز دمینیله شدن نظیر MS و خواص درمانی بالقوه کانابینویید می باشند. |
بخشی از مقاله انگلیسی: Inflammation, autoimmune response, demyelination and axonal damage are thought to participate in the pathogenesis of multiple sclerosis (MS). Understanding whether axonal damage causes or originates from demyelination is a crucial issue. Excitotoxic processes may be responsible for white matter and axonal damage. Experimental and clinical studies indicate that cannabinoids could prove efficient in the treatment of MS. Using a chronic model of MS in mice, we show here that clinical signs and axonal damage in the spinal cord were reduced by the AMPA antagonist, NBQX. Amelioration of symptomatology by the synthetic cannabinoid HU210 was also accompanied by a reduction of axonal damage in this model. Moreover, HU210 reduced AMPA-induced excitotoxicity both in vivo and in vitro through the obligatory activation of both CB1 and CB2 cannabinoid receptors. Together, these data underline the implication of excitotoxic processes in demyelinating pathologies such as MS and the potential therapeutic properties of cannabinoids. © 2006 Elsevier Inc. All rights reserved. Keywords: Multiple sclerosis; TMEV; Axonal damage; Excitotoxicity; Cannabinoids Introduction Multiple sclerosis (MS) is the most common chronic demyelinating disease of the central nervous system (CNS) in humans and leads to motor and sensory deficits, tremor and ataxia. While demyelination is considered as the main element in the pathology of MS, the deleterious processes leading to neurological decline include chronic inflammation, infiltration of T cells and macrophages, axonal damage, and autoimmune response against myelin. However, the way these different processes articulate with each other remains controversial. As demyelination does not necessarily correlate with the severity of neurological decline, an important issue to understand is the timing of axonal damage in this pathology, to characterize it as a cause or as a consequence of demyelination. In the Theiler’s murine encephalomyelitis virusinduced demyelinating disease (TMEV-IDD)-model of MS, Tsunoda et al. (2003) suggested that demyelination could be secondary to axonal damage. Moreover, pioneer studies using experimental allergic encephalomyelitis (EAE) as a model of MS suggested that excitotoxic processes could induce axonal damage and may represent a key element in the pathogenesis of MS (Smith et al., 2000; Pitt et al., 2000). Finally, antagonising α-amino-3- hydroxy-5-methyl-4-isoxazolepropionate (AMPA) glutamatergic receptors led to lesser axonal damage and to better neurological score in EAE (Smith et al., 2000; Pitt et al., 2000). Cannabinoids form a class of molecules that include active components of marijuana, endogenous ligands (endocannabinoids), and a variety of synthetic compounds. They induce their effects through activation of two G-protein-coupled receptors termed CB1 and CB2, and several yet-to-be-cloned receptors (Howlett et al., 2002) which might mediate some of the effects of cannabinoids. Therapeutic properties have been attributed to cannabinoids in various SNC pathologies including Parkinson’s disease (Lastres-Becker et al., 2005), Alzheimer’s disease (Ramirez et al., 2005), head trauma (Panikashvili et al., 2001) and MS. (Pryce et al., 2003) Arévalo-Martín and collaborators showed in 2003 that cannabinoids could exert therapeutic actions in the TMEV-IDD model of MS, reducing motor impairment and inflammation, and eventually promoting remyelination. However, the precise mechanisms promoting these beneficial effects of cannabinoids remain to be more clearly elucidated. Several studies described neuroprotective actions of cannabinoids in different in vitro and in vivo models (Sarne and www.elsevier.com/locate/ymcne Mol. Cell. Neurosci. 34 (2007) 551–561 ⁎ Corresponding author. Fax: +34 91 585 47 54. E-mail address: docagne@cajal.csic.es (F. Docagne). Available online on ScienceDirect (www.sciencedirect.com). 1044-7431/$ – see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.mcn.2006.12.005 Mechoulam, 2005), including cellular models of excitotoxicity (Molina-Holgado et al., 2005; Kim et al., 2006). This neuroprotective effects is thought to be related to the capacity of cannabinoids to inhibit glutamatergic transmission (Domenici et al., 2006). Glial cells, and particularly astrocytes, have been implicated in the mediation of the effects of several neuroprotective agents, including cytokines such as TGF-β (Docagne et al., 2002). Astrocytes might participate in the neuroprotective action of cannabinoids as they may express both CB1 and CB2 receptors (Sheng et al., 2005). A related issue is the relative participation of CB1 and CB2 in cannabinoid-induced neuroprotective effects. These two last questions are addressed in the present study. The present work aims at determining as to whether excitotoxic processes are implicated in the progression of TMEV-IDD. The relationship between excitotoxicity and axonal damage has also been studied in this chronic model of MS. Finally, we studied the therapeutic potential of cannabinoids in this context, for their protective activity against excitotoxicity. |