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      Scolopendra subspinipes mutilans attenuates neuroinflammation in symptomatic hSOD1 G93A mice

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          Abstract

          Background

          Amyotrophic lateral sclerosis (ALS) is a progressive, adult-onset neurodegenerative disorder characterized by selective motor neuron death in the spinal cord, brainstem, and motor cortex. Neuroinflammation is one of several pathological causes of degenerating motor neurons and is induced by activated microglial cells and astrocytes in ALS.

          Scolopendra subspinipes mutilans (SSM) is utilized in traditional Chinese and Korean medicine for the treatment of a variety of diseases, such as cancer, apoplexy, and epilepsy. However, the mechanisms underlying the effects of SSM are currently unclear, even though SSM increases immune and antibiotic activity.

          Methods

          To determine the effects of SSM on symptomatic hSOD1 G93A transgenic mice, SSM (2.5 μℓ/g) was injected bilaterally at the Zusanli (ST36) acupoint three times per week for two weeks. The effects of SSM treatment on anti-neuroinflammation in the brainstem and spinal cord of hSOD1 G93A mice were assessed via Nissl and Fluoro-Jade B (FJB) staining, and immunohistochemistry using Iba-1, CD14, HO1, and NQO1 proteins was evaluated by Western blotting.

          Results

          In this study, we investigated whether SSM affects neuroinflammation in the spinal cord of symptomatic hSOD1 G93A transgenic mice. We found that SSM treatment attenuated the loss of motor neurons and reduced the activation of microglial cells and astrocytes. Furthermore, we demonstrated that SSM administration in this animal model of ALS suppressed oxidative stress in the brainstem and spinal cord by 1.6- and 1.8-fold, respectively.

          Conclusions

          Our findings suggest that SSM, which has previously been used in complementary and alternative medicine (CAM), might also be considered as an anti-neuroinflammatory therapy for neurodegenerative diseases.

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          Most cited references29

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          Inflammation and Alzheimer's disease.

          Inflammation clearly occurs in pathologically vulnerable regions of the Alzheimer's disease (AD) brain, and it does so with the full complexity of local peripheral inflammatory responses. In the periphery, degenerating tissue and the deposition of highly insoluble abnormal materials are classical stimulants of inflammation. Likewise, in the AD brain damaged neurons and neurites and highly insoluble amyloid beta peptide deposits and neurofibrillary tangles provide obvious stimuli for inflammation. Because these stimuli are discrete, microlocalized, and present from early preclinical to terminal stages of AD, local upregulation of complement, cytokines, acute phase reactants, and other inflammatory mediators is also discrete, microlocalized, and chronic. Cumulated over many years, direct and bystander damage from AD inflammatory mechanisms is likely to significantly exacerbate the very pathogenic processes that gave rise to it. Thus, animal models and clinical studies, although still in their infancy, strongly suggest that AD inflammation significantly contributes to AD pathogenesis. By better understanding AD inflammatory and immunoregulatory processes, it should be possible to develop anti-inflammatory approaches that may not cure AD but will likely help slow the progression or delay the onset of this devastating disorder.
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            Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation.

            Mutations of human Cu,Zn superoxide dismutase (SOD) are found in about 20 percent of patients with familial amyotrophic lateral sclerosis (ALS). Expression of high levels of human SOD containing a substitution of glycine to alanine at position 93--a change that has little effect on enzyme activity--caused motor neuron disease in transgenic mice. The mice became paralyzed in one or more limbs as a result of motor neuron loss from the spinal cord and died by 5 to 6 months of age. The results show that dominant, gain-of-function mutations in SOD contribute to the pathogenesis of familial ALS.
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              Fluoro-Jade: a novel fluorochrome for the sensitive and reliable histochemical localization of neuronal degeneration.

              Fluoro-Jade is an anionic fluorochrome capable of selectively staining degenerating neurons in brain slices. The histochemical application of Fluoro-Jade results in a simple, sensitive and reliable method for staining degenerating neurons and their processes. The technique will detect neuronal degeneration resulting from exposure to a variety of neurotoxic insults. Fluoro-Jade can be combined with other fluorescent methodologies including immunofluorescence, fluorescent axonal tract tracing, and fluorescent Nissl counterstaining. Compared to conventional methodologies, Fluoro-Jade is a more sensitive and definitive marker of neuronal degeneration than hematoxylin and eosin (H&E) or Nissl type stains, while being comparably sensitive yet considerably simpler and more reliable than suppressed silver techniques.
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                Author and article information

                Contributors
                Journal
                J Neuroinflammation
                J Neuroinflammation
                Journal of Neuroinflammation
                BioMed Central
                1742-2094
                2013
                29 October 2013
                : 10
                : 131
                Affiliations
                [1 ]Department of Medial Research, Korea Institute of Oriental Medicine, 483 Expo-ro, Yuseong-gu, Daejeon 305-811, Republic of Korea
                [2 ]Department of Internal Medicine, Wonkwang University of Medical School, Iksan, Republic of Korea
                [3 ]Department of Neurology, Inam Neuroscience Research Center, Sanbon Medical Center, College of Medicine, Wonkwang University, Iksan, Republic of Korea
                [4 ]Department of Acupuncture & Moxibustion, Wonkwang University Gwangju Oriental Hospital, 543-8, Juweol1-Dong, Nam-Gu, Gwangju 503-310, Republic of Korea
                Article
                1742-2094-10-131
                10.1186/1742-2094-10-131
                4231348
                24168240
                9865fda0-ab25-4bdc-95d1-7d394fdd551c
                Copyright © 2013 Cai et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 1 July 2013
                : 7 October 2013
                Categories
                Research

                Neurosciences
                amyotrophic lateral sclerosis,scolopendra subspinipes mutilans,neuroinflammation

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