کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6277162 | 1295748 | 2010 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Spinal upregulation of glutamate transporter GLT-1 by ceftriaxone: therapeutic efficacy in a range of experimental nervous system disorders
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کلمات کلیدی
MOGP-gpTBS-TCCIGLT-1EAEGFAPOpioid - opioidAstrocyte - آستروسیتchronic constriction injury - آسیب زدگی مزمنAllodynia - آلودینیا experimental autoimmune encephalomyelitis - آنسفالومیلیت خودایمنی تجربیSpinal cord - طناب نخاعیCSF - مایع مغزی نخاعیCerebrospinal fluid - مایع مغزی نخاعیMultiple sclerosis - مولتیپل اسکلروزیس(ام اس)Hyperalgesia - پردردی یا هایپرآلژزیGlial fibrillary acidic protein - پروتئین اسیدی فیبریلاسیون گلایالmyelin oligodendrocyte glycoprotein - گلیکوپروتئین الیگودندروسیت میلین
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Glutamate neurotransmission is highly regulated, largely by glutamate transporters. In the spinal cord, the glutamate transporter GLT-1 is primarily responsible for glutamate clearance. Downregulation of GLT-1 can occur in activated astrocytes, and is associated with increased extracellular glutamate and neuroexcitation. Among other conditions, astrocyte activation occurs following repeated opioids and in models of chronic pain. If GLT-1 downregulation occurs in these states, GLT-1 could be a pharmacological target for improving opioid efficacy and controlling chronic pain. The present studies explored whether daily intrathecal treatment of rats with ceftriaxone, a β-lactam antibiotic that upregulates GLT-1 expression, could prevent development of hyperalgesia and allodynia following repeated morphine, reverse pain arising from central or peripheral neuropathy, and reduce glial activation in these models. Ceftriaxone pre-treatment attenuated the development of hyperalgesia and allodynia in response to repeated morphine, and prevented associated astrocyte activation. In a model of multiple sclerosis (experimental autoimmune encephalomyelitis; EAE), ceftriaxone reversed tactile allodynia and halted the progression of motor weakness and paralysis. Similarly, ceftriaxone reversed tactile allodynia induced by chronic constriction nerve injury (CCI). EAE and CCI each significantly reduced the expression of membrane-bound, dimerized GLT-1 protein in lumbar spinal cord, an effect normalized by ceftriaxone. Lastly, ceftriaxone normalized CCI- and EAE-induced astrocyte activation in lumbar spinal cord. Together, these data indicate that increasing spinal GLT-1 expression attenuates opioid-induced paradoxical pain, alleviates neuropathic pain, and suppresses associated glial activation. GLT-1 therefore may be a therapeutic target that could improve available treatment options for patients with chronic pain.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 169, Issue 4, 15 September 2010, Pages 1888-1900
Journal: Neuroscience - Volume 169, Issue 4, 15 September 2010, Pages 1888-1900
نویسندگان
K.M. Ramos, M.T. Lewis, K.N. Morgan, N.Y. Crysdale, J.L. Kroll, F.R. Taylor, J.A. Harrison, E.M. Sloane, S.F. Maier, L.R. Watkins,