{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T14:16:16Z","timestamp":1774361776468,"version":"3.50.1"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T00:00:00Z","timestamp":1573689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T00:00:00Z","timestamp":1573689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2014\/06892-3"],"award-info":[{"award-number":["2014\/06892-3"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2013\/16168-8"],"award-info":[{"award-number":["2013\/16168-8"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/02895-6"],"award-info":[{"award-number":["2017\/02895-6"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2018\/05006-0"],"award-info":[{"award-number":["2018\/05006-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["300553\/2013-9"],"award-info":[{"award-number":["300553\/2013-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["303085\/2017-7"],"award-info":[{"award-number":["303085\/2017-7"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The development of new therapeutic strategies to treat amyotrophic lateral sclerosis (ALS) is of utmost importance. The use of cyclic nitroxides such as tempol may provide neuroprotection and improve lifespan. We investigated whether tempol (50\u2009mg\/kg) presents therapeutic potential in SOD1<jats:sup>G93A<\/jats:sup> transgenic mice.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Tempol treatment began at the asymptomatic phase of the disease (10th week) and was administered every other day until week 14, after which it was administered twice a week until the final stage of the disease. The animals were sacrificed at week 14 (initial stage of symptoms\u2014ISS) and at the end stage (ES) of the disease. The lumbar spinal cord of the animals was dissected and processed for use in the following techniques: Nissl staining to evaluate neuronal survival; immunohistochemistry to evaluate astrogliosis and microgliosis (ISS and ES); qRT-PCR to evaluate the expression of neurotrophic factors and pro-inflammatory cytokines (ISS); and transmission electron microscopy to evaluate the alpha-motoneurons (ES). Behavioral analyses considering the survival of animals, bodyweight loss, and Rotarod motor performance test started on week 10 and were performed every 3\u2009days until the end-stage of the disease.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The results revealed that treatment with tempol promoted greater neuronal survival (23%) at ISS compared to untreated animals, which was maintained until ES. The intense reactivity of astrocytes and microglia observed in vehicle animals was reduced in the lumbar spinal cords of the animals treated with tempol. In addition, the groups treated with tempol showed reduced expression of proinflammatory cytokines (<jats:italic>IL1\u03b2<\/jats:italic> and <jats:italic>TNF\u03b1<\/jats:italic>) and a three-fold decrease in the expression of <jats:italic>TGF\u03b21<\/jats:italic> at ISS compared with the group treated with vehicle.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Altogether, our results indicate that treatment with tempol has beneficial effects, delaying the onset of the disease by enhancing neuronal survival and decreasing glial cell reactivity during ALS progression in SOD1<jats:sup>G93A<\/jats:sup> mice.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12974-019-1598-x","type":"journal-article","created":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T14:03:10Z","timestamp":1573740190000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Tempol improves neuroinflammation and delays motor dysfunction in a mouse model (SOD1G93A) of ALS"],"prefix":"10.1186","volume":"16","author":[{"given":"Gabriela Bortolan\u00e7a","family":"Chiarotto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciana Politti","family":"Cartarozzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matheus","family":"Perez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia Perussi","family":"Biscola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aline Barroso","family":"Spejo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda","family":"Gubert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcondes","family":"Fran\u00e7a Junior","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ros\u00e1lia","family":"Mendez-Otero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4224-4575","authenticated-orcid":false,"given":"Alexandre Leite Rodrigues","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,11,14]]},"reference":[{"issue":"11","key":"1598_CR1","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1038\/nrneurol.2011.153","volume":"7","author":"O Hardiman","year":"2011","unstructured":"Hardiman O, van den Berg LH, Kiernan MC. Clinical diagnosis and management of amyotrophic lateral sclerosis. Nat Rev Neurol. 2011;7(11):639\u201349.","journal-title":"Nat Rev Neurol"},{"issue":"2","key":"1598_CR2","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.expneurol.2003.10.004","volume":"185","author":"LR Fischer","year":"2004","unstructured":"Fischer LR, Culver DG, Tennant P, Davis AA, Wang M, Castellano-Sanchez A, et al. Amyotrophic lateral sclerosis is a distal axonopathy: evidence in mice and man. Exp Neurol. 2004;185(2):232\u201340.","journal-title":"Exp Neurol"},{"issue":"2","key":"1598_CR3","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1159\/000351153","volume":"41","author":"A Chio","year":"2013","unstructured":"Chio A, Logroscino G, Traynor BJ, Collins J, Simeone JC, Goldstein LA, et al. Global epidemiology of amyotrophic lateral sclerosis: a systematic review of the published literature. Neuroepidemiology. 2013;41(2):118\u201330.","journal-title":"Neuroepidemiology."},{"issue":"4","key":"1598_CR4","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/nrn3430","volume":"14","author":"W Robberecht","year":"2013","unstructured":"Robberecht W, Philips T. The changing scene of amyotrophic lateral sclerosis. Nat Rev Neurosci. 2013;14(4):248\u201364.","journal-title":"Nat Rev Neurosci"},{"issue":"9769","key":"1598_CR5","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1016\/S0140-6736(10)61156-7","volume":"377","author":"MC Kiernan","year":"2011","unstructured":"Kiernan MC, Vucic S, Cheah BC, Turner MR, Eisen A, Hardiman O, et al. Amyotrophic lateral sclerosis. Lancet. 2011;377(9769):942\u201355.","journal-title":"Lancet."},{"issue":"Pt B","key":"1598_CR6","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.expneurol.2014.05.015","volume":"262","author":"T Philips","year":"2014","unstructured":"Philips T, Rothstein JD. Glial cells in amyotrophic lateral sclerosis. Exp Neurol. 2014;262(Pt B):111\u201320.","journal-title":"Exp Neurol"},{"issue":"4","key":"1598_CR7","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1007\/s11481-013-9489-x","volume":"8","author":"W Zhao","year":"2013","unstructured":"Zhao W, Beers DR, Appel SH. Immune-mediated mechanisms in the pathoprogression of amyotrophic lateral sclerosis. J Neuroimmune Pharmacol. 2013;8(4):888\u201399.","journal-title":"J Neuroimmune Pharmacol"},{"issue":"5","key":"1598_CR8","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1016\/j.neuron.2014.01.013","volume":"81","author":"AE Frakes","year":"2014","unstructured":"Frakes AE, Ferraiuolo L, Haidet-Phillips AM, Schmelzer L, Braun L, Miranda CJ, et al. Microglia induce motor neuron death via the classical NF-\u03baB pathway in amyotrophic lateral sclerosis. Neuron. 2014;81(5):1009\u201323.","journal-title":"Neuron."},{"key":"1598_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.nbd.2015.02.017","volume":"77","author":"BJ Murdock","year":"2015","unstructured":"Murdock BJ, Bender DE, Segal BM, Feldman EL. The dual roles of immunity in ALS: injury overrides protection. Neurobiol Dis. 2015;77:1\u201312.","journal-title":"Neurobiol Dis"},{"issue":"8","key":"1598_CR10","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.tins.2014.05.006","volume":"37","author":"S Vucic","year":"2014","unstructured":"Vucic S, Rothstein JD, Kiernan MC. Advances in treating amyotrophic lateral sclerosis: insights from pathophysiological studies. Trends Neurosci. 2014;37(8):433\u201342.","journal-title":"Trends Neurosci"},{"issue":"18","key":"1598_CR11","doi-asserted-by":"publisher","first-page":"15728","DOI":"10.18632\/oncotarget.4786","volume":"6","author":"F Endo","year":"2015","unstructured":"Endo F, Yamanaka K. Astrocytic TGF-\u03b21: detrimental factor in ALS. Oncotarget. 2015;6(18):15728\u20139.","journal-title":"Oncotarget."},{"issue":"3","key":"1598_CR12","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/nn2047","volume":"11","author":"K Yamanaka","year":"2008","unstructured":"Yamanaka K, Chun SJ, Boillee S, Fujimori-Tonou N, Yamashita H, Gutmann DH, et al. Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nat Neurosci. 2008;11(3):251\u20133.","journal-title":"Nat Neurosci"},{"issue":"6","key":"1598_CR13","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1083\/jcb.200908164","volume":"187","author":"H Ilieva","year":"2009","unstructured":"Ilieva H, Polymenidou M, Cleveland DW. Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond. J Cell Biol. 2009;187(6):761\u201372.","journal-title":"J Cell Biol"},{"issue":"1 Suppl","key":"1598_CR14","doi-asserted-by":"publisher","first-page":"S76","DOI":"10.1097\/00003246-200301001-00011","volume":"31","author":"C Thiemermann","year":"2003","unstructured":"Thiemermann C. Membrane-permeable radical scavengers (tempol) for shock, ischemia-reperfusion injury, and inflammation. Crit Care Med. 2003;31(1 Suppl):S76\u201384.","journal-title":"Crit Care Med"},{"issue":"10","key":"1598_CR15","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1089\/ars.2007.1722","volume":"9","author":"BP Soule","year":"2007","unstructured":"Soule BP, Hyodo F, Matsumoto K, Simone NL, Cook JA, Krishna MC, et al. Therapeutic and clinical applications of nitroxide compounds. Antioxid Redox Signal. 2007;9(10):1731\u201343.","journal-title":"Antioxid Redox Signal"},{"issue":"1","key":"1598_CR16","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1590\/S0001-37652008000100013","volume":"80","author":"O Augusto","year":"2008","unstructured":"Augusto O, Trindade DF, Linares E, Vaz SM. Cyclic nitroxides inhibit the toxicity of nitric oxide-derived oxidants: mechanisms and implications. Anais da Academia Brasileira de Ciencias. 2008;80(1):179\u201389.","journal-title":"Anais da Academia Brasileira de Ciencias"},{"issue":"1","key":"1598_CR17","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1007\/s12035-013-8508-5","volume":"49","author":"A Sunkaria","year":"2014","unstructured":"Sunkaria A, Sharma DR, Wani WY, Gill KD. Attenuation of dichlorvos-induced microglial activation and neuronal apoptosis by 4-hydroxy TEMPO. Mol Neurobiol. 2014;49(1):163\u201375.","journal-title":"Mol Neurobiol"},{"key":"1598_CR18","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.freeradbiomed.2014.08.029","volume":"77","author":"P Dohare","year":"2014","unstructured":"Dohare P, Hyzinski-Garcia MC, Vipani A, Bowens NH, Nalwalk JW, Feustel PJ, et al. The neuroprotective properties of the superoxide dismutase mimetic tempol correlate with its ability to reduce pathological glutamate release in a rodent model of stroke. Free Radic Biol Med. 2014;77:168\u201382.","journal-title":"Free Radic Biol Med"},{"key":"1598_CR19","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.bbi.2017.02.018","volume":"62","author":"S Neil","year":"2017","unstructured":"Neil S, Huh J, Baronas V, Li X, McFarland HF, Cherukuri M, et al. Oral administration of the nitroxide radical TEMPOL exhibits immunomodulatory and therapeutic properties in multiple sclerosis models. Brain Behav Immun. 2017;62:332\u201343.","journal-title":"Brain Behav Immun"},{"issue":"6","key":"1598_CR20","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1007\/s00210-016-1234-6","volume":"389","author":"MR Ali","year":"2016","unstructured":"Ali MR, Abo-Youssef AM, Messiha BA, Khattab MM. Tempol and perindopril protect against lipopolysaccharide-induced cognition impairment and amyloidogenesis by modulating brain-derived neurotropic factor, neuroinflammation and oxido-nitrosative stress. Naunyn Schmiedeberg's Arch Pharmacol. 2016;389(6):637\u201356.","journal-title":"Naunyn Schmiedeberg's Arch Pharmacol"},{"issue":"1\u20133","key":"1598_CR21","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.ejphar.2006.08.022","volume":"549","author":"T Lipman","year":"2006","unstructured":"Lipman T, Tabakman R, Lazarovici P. Neuroprotective effects of the stable nitroxide compound Tempol on 1-methyl-4-phenylpyridinium ion-induced neurotoxicity in the nerve growth factor-differentiated model of pheochromocytoma PC12 cells. Eur J Pharmacol. 2006;549(1\u20133):50\u20137.","journal-title":"Eur J Pharmacol"},{"issue":"26","key":"1598_CR22","doi-asserted-by":"crossref","first-page":"42808","DOI":"10.18632\/oncotarget.17057","volume":"8","author":"L Wang","year":"2017","unstructured":"Wang L, Li B, Quan MY, Li L, Chen Y, Tan GJ, et al. Mechanism of oxidative stress p38MAPK-SGK1 signaling axis in experimental autoimmune encephalomyelitis (EAE). Oncotarget. 2017;8(26):42808\u201316.","journal-title":"Oncotarget."},{"key":"1598_CR23","doi-asserted-by":"crossref","unstructured":"Chiarotto GB, Drumond L, Cavarretto G, Bombeiro AL, de Oliveira AL. Neuroprotective effect of tempol (4 hydroxy-tempo) on neuronal death induced by sciatic nerve transection in neonatal rats. Brain Res Bull. 2014.","DOI":"10.1016\/j.brainresbull.2014.04.010"},{"issue":"2","key":"1598_CR24","doi-asserted-by":"publisher","first-page":"C650","DOI":"10.1152\/ajpcell.00037.2007","volume":"293","author":"JN Edwards","year":"2007","unstructured":"Edwards JN, Macdonald WA, van der Poel C, Stephenson DG. O2(*-) production at 37 degrees C plays a critical role in depressing tetanic force of isolated rat and mouse skeletal muscle. Am J Physiol Cell Physiol. 2007;293(2):C650\u201360.","journal-title":"Am J Physiol Cell Physiol"},{"key":"1598_CR25","doi-asserted-by":"crossref","unstructured":"Burns DP, Ali I, Rieux C, Healy J, Jasionek G, O'Halloran KD. Tempol Supplementation restores diaphragm force and metabolic enzyme activities in mdx mice. Antioxidants (Basel). 2017;6(4):1-16.","DOI":"10.3390\/antiox6040101"},{"issue":"1\u20132","key":"1598_CR26","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/S0022-510X(00)00423-8","volume":"180","author":"P Kennel","year":"2000","unstructured":"Kennel P, Revah F, Bohme GA, Bejuit R, Gallix P, Stutzmann JM, et al. Riluzole prolongs survival and delays muscle strength deterioration in mice with progressive motor neuronopathy (pmn). J Neurol Sci. 2000;180(1\u20132):55\u201361.","journal-title":"J Neurol Sci"},{"issue":"19","key":"1598_CR27","doi-asserted-by":"publisher","first-page":"3782","DOI":"10.1093\/hmg\/ddq293","volume":"19","author":"S Corti","year":"2010","unstructured":"Corti S, Nizzardo M, Nardini M, Donadoni C, Salani S, Simone C, et al. Systemic transplantation of c-kit+ cells exerts a therapeutic effect in a model of amyotrophic lateral sclerosis. Hum Mol Genet. 2010;19(19):3782\u201396.","journal-title":"Hum Mol Genet"},{"issue":"Pt 1","key":"1598_CR28","first-page":"37","volume":"80","author":"M Abercrombie","year":"1946","unstructured":"Abercrombie M, Johnson ML. Quantitative histology of Wallerian degeneration: I. nuclear population in rabbit sciatic nerve. J Anat. 1946;80(Pt 1):37\u201350.","journal-title":"J Anat"},{"issue":"51","key":"1598_CR29","doi-asserted-by":"publisher","first-page":"17843","DOI":"10.1073\/pnas.0408154101","volume":"101","author":"AL Oliveira","year":"2004","unstructured":"Oliveira AL, Thams S, Lidman O, Piehl F, H\u00f6kfelt T, K\u00e4rre K, et al. A role for MHC class I molecules in synaptic plasticity and regeneration of neurons after axotomy. Proc Natl Acad Sci U S A. 2004;101(51):17843\u20138.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"1598_CR30","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(\u2212Delta Delta C(T)) method. Methods. 2001;25(4):402\u20138.","journal-title":"Methods."},{"issue":"5","key":"1598_CR31","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1016\/j.bbi.2010.12.008","volume":"25","author":"DR Beers","year":"2011","unstructured":"Beers DR, Zhao W, Liao B, Kano O, Wang J, Huang A, et al. Neuroinflammation modulates distinct regional and temporal clinical responses in ALS mice. Brain Behav Immun. 2011;25(5):1025\u201335.","journal-title":"Brain Behav Immun"},{"issue":"10","key":"1598_CR32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0109833","volume":"9","author":"VM Harandi","year":"2014","unstructured":"Harandi VM, Lindquist S, Kolan SS, Brannstrom T, Liu JX. Analysis of neurotrophic factors in limb and extraocular muscles of mouse model of amyotrophic lateral sclerosis. PLoS One. 2014;9(10):e109833.","journal-title":"PLoS One"},{"issue":"2","key":"1598_CR33","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1006\/exnr.2002.8011","volume":"177","author":"BM K\u00fcst","year":"2002","unstructured":"K\u00fcst BM, Copray JC, Brouwer N, Troost D, Boddeke HW. Elevated levels of neurotrophins in human biceps brachii tissue of amyotrophic lateral sclerosis. Exp Neurol. 2002;177(2):419\u201327.","journal-title":"Exp Neurol"},{"issue":"4","key":"1598_CR34","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/j.celrep.2015.03.053","volume":"11","author":"F Endo","year":"2015","unstructured":"Endo F, Komine O, Fujimori-Tonou N, Katsuno M, Jin S, Watanabe S, et al. Astrocyte-derived TGF-\u03b21 accelerates disease progression in ALS mice by interfering with the neuroprotective functions of microglia and T cells. Cell Rep. 2015;11(4):592\u2013604.","journal-title":"Cell Rep"},{"issue":"2","key":"1598_CR35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055868","volume":"8","author":"E Linares","year":"2013","unstructured":"Linares E, Seixas LV, dos Prazeres JN, Ladd FV, Ladd AA, Coppi AA, et al. Tempol moderately extends survival in a hSOD1(G93A) ALS rat model by inhibiting neuronal cell loss, oxidative damage and levels of non-native hSOD1(G93A) forms. PLoS One. 2013;8(2):e55868.","journal-title":"PLoS One"},{"issue":"4","key":"1598_CR36","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1007\/s13311-012-0140-y","volume":"9","author":"R Mancuso","year":"2012","unstructured":"Mancuso R, Oliv\u00e1n S, Rando A, Casas C, Osta R, Navarro X. Sigma-1R agonist improves motor function and motoneuron survival in ALS mice. Neurotherapeutics. 2012;9(4):814\u201326.","journal-title":"Neurotherapeutics."},{"issue":"21","key":"1598_CR37","doi-asserted-by":"publisher","first-page":"5535","DOI":"10.1523\/JNEUROSCI.1139-07.2007","volume":"27","author":"C Rouaux","year":"2007","unstructured":"Rouaux C, Panteleeva I, Ren\u00e9 F, Gonzalez de Aguilar JL, Echaniz-Laguna A, Dupuis L, et al. Sodium valproate exerts neuroprotective effects in vivo through CREB-binding protein-dependent mechanisms but does not improve survival in an amyotrophic lateral sclerosis mouse model. J Neurosci. 2007;27(21):5535\u201345.","journal-title":"J Neurosci"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-019-1598-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12974-019-1598-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-019-1598-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T00:20:03Z","timestamp":1605226803000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-019-1598-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,14]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["1598"],"URL":"https:\/\/doi.org\/10.1186\/s12974-019-1598-x","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,14]]},"assertion":[{"value":"25 February 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 September 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 November 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All procedures were carried out with the approval of the Ethics Committee on Animal Experimentation of the University of Campinas, SP, Brazil (CEUA\/UNICAMP, protocol 3304-1 and 4501-1\/2017) and in accordance with the ethical principles regulated by the National Council of Animal Experimentation (CONCEA).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"218"}}