Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2017

Open Access 01-12-2017 | Research

Exercise attenuates neurological deficits by stimulating a critical HSP70/NF-κB/IL-6/synapsin I axis in traumatic brain injury rats

Authors: Chung-Ching Chio, Hung-Jung Lin, Yu-Feng Tian, Yu-Chieh Chen, Mao-Tsun Lin, Cheng-Hsien Lin, Ching-Ping Chang, Chien-Chin Hsu

Published in: Journal of Neuroinflammation | Issue 1/2017

Login to get access

Abstract

Background

Despite previous evidence for a potent inflammatory response after a traumatic brain injury (TBI), it is unknown whether exercise preconditioning (EP) improves outcomes after a TBI by modulating inflammatory responses.

Methods

We performed quantitative real-time PCR (qPCR) to quantify the genes encoding 84 cytokines and chemokines in the peripheral blood and used ELISA to determine both the cerebral and blood levels of interleukin-6 (IL-6). We also performed the chromatin immunoprecipitation (ChIP) assay to evaluate the extent of nuclear factor kappa-B (NF-κB) binding to the DNA elements in the IL-6 promoter regions. Also, we adopted the Western blotting assay to measure the cerebral levels of heat shock protein (HSP) 70, synapsin I, and β-actin. Finally, we performed both histoimmunological and behavioral assessment to measure brain injury and neurological deficits, respectively.

Results

We first demonstrated that TBI upregulated nine pro-inflammatory and/or neurodegenerative messenger RNAs (mRNAs) in the peripheral blood such as CXCL10, IL-18, IL-16, Cd-70, Mif, Ppbp, Ltd, Tnfrsf 11b, and Faslg. In addition to causing neurological injuries, TBI also upregulated the following 14 anti-inflammatory and/or neuroregenerative mRNAs in the peripheral blood such as Ccl19, Ccl3, Cxcl19, IL-10, IL-22, IL-6, Bmp6, Ccl22, IL-7, Bmp7, Ccl2, Ccl17, IL-1rn, and Gpi. Second, we observed that EP inhibited both neurological injuries and six pro-inflammatory and/or neurodegenerative genes (Cxcl10, IL-18, IL-16, Cd70, Mif, and Faslg) but potentiated four anti-inflammatory and/or neuroregenerative genes (Bmp6, IL-10, IL-22, and IL-6). Prior depletion of cerebral HSP70 with gene silence significantly reversed the beneficial effects of EP in reducing neurological injuries and altered gene profiles after a TBI. A positive Pearson correlation exists between IL-6 and HSP70 in the peripheral blood or in the cerebral levels. In addition, gene silence of cerebral HSP70 significantly reduced the overexpression of NF-κB, IL-6, and synapsin I in the ipsilateral brain regions after an EP in rats.

Conclusions

TBI causes neurological deficits associated with stimulating several pro-inflammatory gene profiles but inhibiting several anti-inflammatory gene profiles of cytokines and chemokines. Exercise protects against neurological injuries via stimulating an anti-inflammatory HSP70/NF-κB/IL-6/synapsin I axis in the injured brains.
Literature
1.
Muramatsu R, Takahashi C, Miyake S, Fujimura H, Mochizuki H, Yamashita T. Angiogenesis induced by CNS inflammation promotes neuronal remodeling through vessel-derived prostacyclin. Nat Med. 2012;18:1658–64.CrossRefPubMed
2.
Chio CC, Lin MT, Chang CP. Microglial activation as a compelling target for treating acute traumatic brain injury. Curr Med Chem. 2015;22:759–70.CrossRefPubMed
3.
Csuka E, Hans VH, Ammann E, Trentz O, Kossmann T, Morganti-Kossmann MC. Cell activation and inflammatory response following traumatic axonal injury in the rat. Neuroreport. 2000;11:2587–90.CrossRefPubMed
4.
Morganti-Kossman MC, Lenzlinger PM, Hans V, Stahel P, Csuka E, Ammann E, Stocker R, Trentz O, Kossmann T. Production of cytokines following brain injury: beneficial and deleterious for the damaged tissue. Mol Psychiatry. 1997;2:133–6.CrossRefPubMed
5.
Mondello S, Muller U, Jeromin A, Streeter J, Hayes RL, Wang KK. Blood-based diagnostics of traumatic brain injuries. Expert Rev Mol Diagn. 2011;11:65–78.CrossRefPubMedPubMedCentral
6.
Shein SL, Shellington DK, Exo JL, Jackson TC, Wisniewski SR, Jackson EK, Vagni VA, Bayir H, Clark RS, Dixon CE, et al. Hemorrhagic shock shifts the serum cytokine profile from pro- to anti-inflammatory after experimental traumatic brain injury in mice. J Neurotrauma. 2014;31:1386–95.CrossRefPubMedPubMedCentral
7.
8.
Pittet JF, Lee H, Morabito D, Howard MB, Welch WJ, Mackersie RC. Serum levels of Hsp 72 measured early after trauma correlate with survival. J Trauma. 2002;52:611–7. discussion 17.PubMed
9.
Chen M, Clark RS, Kochanek PM, Chen J, Schiding JK, Stetler RA, Simon RP, Graham SH. 72-kDa heat shock protein and mRNA expression after controlled cortical impact injury with hypoxemia in rats. J Neurotrauma. 1998;15:171–81.CrossRefPubMed
10.
Hergenroeder GW, Moore AN, McCoy Jr JP, Samsel L, Ward 3rd NH, Clifton GL, Dash PK. Serum IL-6: a candidate biomarker for intracranial pressure elevation following isolated traumatic brain injury. J Neuroinflammation. 2010;7:19.CrossRefPubMedPubMedCentral
11.
Kossmann T, Hans VH, Imhof HG, Stocker R, Grob P, Trentz O, Morganti-Kossmann C. Intrathecal and serum interleukin-6 and the acute-phase response in patients with severe traumatic brain injuries. Shock. 1995;4:311–7.CrossRefPubMed
12.
Frugier T, Morganti-Kossmann MC, O’Reilly D, McLean CA. In situ detection of inflammatory mediators in post mortem human brain tissue after traumatic injury. J Neurotrauma. 2010;27:497–507.CrossRefPubMed
13.
Howell JM, Winstone TL, Coorssen JR, Turner RJ. An evaluation of in vitro protein-protein interaction techniques: assessing contaminating background proteins. Proteomics. 2006;6:2050–69.CrossRefPubMed
14.
Kumar RG, Boles JA, Wagner AK. Chronic inflammation after severe traumatic brain injury: characterization and associations with outcome at 6 and 12 months postinjury. J Head Trauma Rehabil. 2015;30:369–81.CrossRefPubMed
15.
Mazzeo AT, Filippini C, Rosato R, Fanelli V, Assenzio B, Piper I, Howells T, Mastromauro I, Berardino M, Ducati A, et al. Multivariate projection method to investigate inflammation associated with secondary insults and outcome after human traumatic brain injury: a pilot study. J Neuroinflammation. 2016;13:157.CrossRefPubMedPubMedCentral
16.
17.
18.
Kushima Y, Hama T, Hatanaka H. Interleukin-6 as a neurotrophic factor for promoting the survival of cultured catecholaminergic neurons in a chemically defined medium from fetal and postnatal rat midbrains. Neurosci Res. 1992;13:267–80.CrossRefPubMed
19.
20.
Liebelt B, Papapetrou P, Ali A, Guo M, Ji X, Peng C, Rogers R, Curry A, Jimenez D, Ding Y. Exercise preconditioning reduces neuronal apoptosis in stroke by up-regulating heat shock protein-70 (heat shock protein-72) and extracellular-signal-regulated-kinase 1/2. Neuroscience. 2010;166:1091–100.CrossRefPubMed
21.
Chen YW, Chen SH, Chou W, Lo YM, Hung CH, Lin MT. Exercise pretraining protects against cerebral ischaemia induced by heat stroke in rats. Br J Sports Med. 2007;41:597–602.CrossRefPubMedPubMedCentral
22.
Chang CK, Chou W, Lin HJ, Huang YC, Tang LY, Lin MT, Chang CP. Exercise preconditioning protects against spinal cord injury in rats by upregulating neuronal and astroglial heat shock protein 72. Int J Mol Sci. 2014;15:19018–36.CrossRefPubMedPubMedCentral
23.
Mörtberg E, Zetterberg H, Nordmark J, Blennow K, Catry C, Decraemer H, Vanmechelen E, Rubertsson S. Plasma tau protein in comatose patients after cardiac arrest treated with therapeutic hypothermia. Acta Anaesthesiol Scand. 2011;55:1132–8.CrossRefPubMed
24.
Randall J, Mortberg E, Provuncher GK, Fournier DR, Duffy DC, Rubertsson S, Blennow K, Zetterberg H, Wilson DH. Tau proteins in serum predict neurological outcome after hypoxic brain injury from cardiac arrest: results of a pilot study. Resuscitation. 2013;84:351–6.CrossRefPubMed
25.
Tsai MC, Chang CP, Peng SW, Jhuang KS, Fang YH, Lin MT, Tsao TC. Therapeutic efficacy of Neuro AiD (MLC 601), a traditional Chinese medicine, in experimental traumatic brain injury. J Neuroimmune Pharmacol. 2015;10:45–54.CrossRefPubMed
26.
Brummelkamp TR, Bernards R, Agami R. A system for stable expression of short interfering RNAs in mammalian cells. Science. 2002;296:550–3.CrossRefPubMed
27.
Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 7th ed. New York: Elsevier Academic Press; 2013.
28.
Chen SF, Hsu CW, Huang WH, Wang JY. Post-injury baicalein improves histological and functional outcomes and reduces inflammatory cytokines after experimental traumatic brain injury. Br J Pharmacol. 2008;155:1279–96.CrossRefPubMedPubMedCentral
29.
Chang MW, Young MS, Lin MT. An inclined plane system with microcontroller to determine limb motor function of laboratory animals. J Neurosci Methods. 2008;168:186–94.CrossRefPubMed
30.
Chang CP, Chio CC, Cheong CU, Chao CM, Cheng BC, Lin MT. Hypoxic preconditioning enhances the therapeutic potential of the secretome from cultured human mesenchymal stem cells in experimental traumatic brain injury. Clin Sci (Lond). 2013;124:165–76.CrossRef
31.
Wu MH, Chio CC, Tsai KJ, Chang CP, Lin NK, Huang CC, Lin MT. Obesity exacerbates rat cerebral ischemic injury through enhancing ischemic adiponectin-containing neuronal apoptosis. Mol Neurobiol. 2015;53:3702–13.CrossRefPubMed
32.
Chio CC, Lin JW, Chang MW, Wang CC, Kuo JR, Yang CZ, Chang CP. Therapeutic evaluation of etanercept in a model of traumatic brain injury. J Neurochem. 2010;115:921–9.CrossRefPubMed
33.
Ghosh CC, Ramaswami S, Juvekar A, Vu HY, Galdieri L, Davidson D, Vancurova I. Gene-specific repression of proinflammatory cytokines in stimulated human macrophages by nuclear IkappaBalpha. J Immunol. 2010;185:3685–93.CrossRefPubMedPubMedCentral
34.
Nakajima H, Kubo T, Semi Y, Itakura M, Kuwamura M, Izawa T, Azuma YT, Takeuchi T. A rapid, targeted, neuron-selective, in vivo knockdown following a single intracerebroventricular injection of a novel chemically modified siRNA in the adult rat brain. J Biotechnol. 2012;157:326–33.CrossRefPubMed
35.
Fujiki M, Kobayashi H, Inoue R, Ishii K. A single oral dose of geranylgeranylacetone attenuates kainic acid-induced seizures and neuronal cell death in rat hippocampus. Brain Res. 2004;1021:281–5.CrossRefPubMed
36.
Zhao Z, Faden AI, Loane DJ, Lipinski MM, Sabirzhanov B, Stoica BA. Neuroprotective effects of geranylgeranylacetone in experimental traumatic brain injury. J Cereb Blood Flow Metab. 2013;33:1897–908.CrossRefPubMedPubMedCentral
37.
Fairbanks SL, Brambrink AM. Preconditioning and postconditioning for neuroprotection: the most recent evidence. Best Pract Res Clin Anaesthesiol. 2010;24:521–34.CrossRefPubMed
38.
Archer T. Influence of physical exercise on traumatic brain injury deficits: scaffolding effect. Neurotox Res. 2012;21:418–34.CrossRefPubMed
39.
Griesbach GS, Hovda DA, Gomez-Pinilla F. Exercise-induced improvement in cognitive performance after traumatic brain injury in rats is dependent on BDNF activation. Brain Res. 2009;1288:105–15.CrossRefPubMedPubMedCentral
40.
Mota BC, Pereira L, Souza MA, Silva LF, Magni DV, Ferreira AP, Oliveira MS, Furian AF, Mazzardo-Martins L, Silva MD, et al. Exercise pre-conditioning reduces brain inflammation and protects against toxicity induced by traumatic brain injury: behavioral and neurochemical approach. Neurotox Res. 2012;21:175–84.CrossRefPubMed
41.
Febbraio MA, Pedersen BK. Muscle-derived interleukin-6: mechanisms for activation and possible biological roles. Faseb J. 2002;16:1335–47.CrossRefPubMed
42.
Pedersen BK, Fischer CP. Beneficial health effects of exercise--the role of IL-6 as a myokine. Trends Pharmacol Sci. 2007;28:152–6.CrossRefPubMed
43.
Phillips C, Baktir MA, Srivatsan M, Salehi A. Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling. Front Cell Neurosci. 2014;8:170.CrossRefPubMedPubMedCentral
44.
Petersen AM, Pedersen BK. The role of IL-6 in mediating the anti-inflammatory effects of exercise. J Physiol Pharmacol. 2006;57 Suppl 10:43–51.PubMed
45.
Ley EJ, Clond MA, Singer MB, Shouhed D, Salim A. IL6 deficiency affects function after traumatic brain injury. J Surg Res. 2011;170:253–6.CrossRefPubMed
46.
Bowen KK, Dempsey RJ, Vemuganti R. Adult interleukin-6 knockout mice show compromised neurogenesis. Neuroreport. 2011;22:126–30.CrossRefPubMed
47.
Monje ML, Toda H, Palmer TD. Inflammatory blockade restores adult hippocampal neurogenesis. Science. 2003;302:1760–5.CrossRefPubMed
48.
Ehrlich DE, Josselyn SA. Plasticity-related genes in brain development and amygdala-dependent learning. Genes Brain Behav. 2016;15:125–43.CrossRefPubMed
49.
Vaynman SS, Ying Z, Yin D, Gomez-Pinilla F. Exercise differentially regulates synaptic proteins associated to the function of BDNF. Brain Res. 2006;1070:124–30.CrossRefPubMed
50.
Fehrenbach E, Schneider ME. Trauma-induced systemic inflammatory response versus exercise-induced immunomodulatory effects. Sports Med. 2006;36:373–84.CrossRefPubMed
51.
Piao CS, Stoica BA, Wu J, Sabirzhanov B, Zhao Z, Cabatbat R, Loane DJ, Faden AI. Late exercise reduces neuroinflammation and cognitive dysfunction after traumatic brain injury. Neurobiol Dis. 2013;54:252–63.CrossRefPubMedPubMedCentral
52.
Koo JW, Russo SJ, Ferguson D, Nestler EJ, Duman RS. Nuclear factor-kappaB is a critical mediator of stress-impaired neurogenesis and depressive behavior. Proc Natl Acad Sci U S A. 2010;107:2669–74.CrossRefPubMedPubMedCentral
53.
Manecka DL, Mahmood SF, Grumolato L, Lihrmann I, Anouar Y. Pituitary adenylate cyclase-activating polypeptide (PACAP) promotes both survival and neuritogenesis in PC12 cells through activation of nuclear factor kappaB (NF-kappaB) pathway: involvement of extracellular signal-regulated kinase (ERK), calcium, and c-REL. J Biol Chem. 2013;288:14936–48.CrossRefPubMedPubMedCentral
54.
Neidl R, Schneider A, Bousiges O, Majchrzak M, Barbelivien A, de Vasconcelos AP, Dorgans K, Doussau F, Loeffler JP, Cassel JC, et al. Late-life environmental enrichment induces acetylation events and nuclear factor kappaB-dependent regulations in the hippocampus of aged rats showing improved plasticity and learning. J Neurosci. 2016;36:4351–61.CrossRefPubMed
55.
Hsieh CL, Kim CC, Ryba BE, Niemi EC, Bando JK, Locksley RM, Liu J, Nakamura MC, Seaman WE. Traumatic brain injury induces macrophage subsets in the brain. Eur J Immunol. 2013;43:2010–22.CrossRefPubMedPubMedCentral
56.
Turtzo LC, Lescher J, Janes L, Dean DD, Budde MD, Frank JA. Macrophagic and microglial responses after focal traumatic brain injury in the female rat. J Neuroinflammation. 2014;11:82.CrossRefPubMedPubMedCentral
57.
Michell-Robinson MA, Touil H, Healy LM, Owen DR, Durafourt BA, Bar-Or A, Antel JP, Moore CS. Roles of microglia in brain development, tissue maintenance and repair. Brain. 2015;138:1138–59.CrossRefPubMed
58.
Kobayashi K, Imagama S, Ohgomori T, Hirano K, Uchimura K, Sakamoto K, Hirakawa A, Takeuchi H, Suzumura A, Ishiguro N, et al. Minocycline selectively inhibits M1 polarization of microglia. Cell Death Dis. 2013;4:e525.CrossRefPubMedPubMedCentral
59.
60.
Tang Y, Le W. Differential roles of M1 and M2 microglia in neurodegenerative diseases. Mol Neurobiol. 2016;53:1181–94.CrossRefPubMed
61.
62.
Kumar A, Stoica BA, Sabirzhanov B, Burns MP, Faden AI, Loane DJ. Traumatic brain injury in aged animals increases lesion size and chronically alters microglial/macrophage classical and alternative activation states. Neurobiol Aging. 2013;34:1397–411.CrossRefPubMed
63.
Niu J, Azfer A, Zhelyabovska O, Fatma S, Kolattukudy PE. Monocyte chemotactic protein (MCP)-1 promotes angiogenesis via a novel transcription factor, MCP-1-induced protein (MCPIP). J Biol Chem. 2008;283:14542–51.CrossRefPubMedPubMedCentral
64.
Stamatovic SM, Keep RF, Mostarica-Stojkovic M, Andjelkovic AV. CCL2 regulates angiogenesis via activation of Ets-1 transcription factor. J Immunol. 2006;177:2651–61.CrossRefPubMed
65.
Martire A, Fernandez B, Buehler A, Strohm C, Schaper J, Zimmermann R, Kolattukudy PE, Schaper W. Cardiac overexpression of monocyte chemoattractant protein-1 in transgenic mice mimics ischemic preconditioning through SAPK/JNK1/2 activation. Cardiovasc Res. 2003;57:523–34.CrossRefPubMed
66.
David S, Kroner A. Repertoire of microglial and macrophage responses after spinal cord injury. Nat Rev Neurosci. 2011;12:388–99.CrossRefPubMed
67.
Himi T, Yoshioka I, Kataura A. Production and gene expression of IL-8-like cytokine GRO/CINC-1 in rat nasal mucosa. Acta Otolaryngol. 1997;117:123–7.CrossRefPubMed
68.
Wang X, Li X, Schmidt DB, Foley JJ, Barone FC, Ames RS, Sarau HM. Identification and molecular characterization of rat CXCR3: receptor expression and interferon-inducible protein-10 binding are increased in focal stroke. Mol Pharmacol. 2000;57:1190–8.PubMed
69.
Clausen F, Lorant T, Lewen A, Hillered L. T lymphocyte trafficking: a novel target for neuroprotection in traumatic brain injury. J Neurotrauma. 2007;24:1295–307.CrossRefPubMed
70.
Ghasemzadeh M, Kaplan ZS, Alwis I, Schoenwaelder SM, Ashworth KJ, Westein E, Hosseini E, Salem HH, Slattery R, McColl SR, et al. The CXCR1/2 ligand NAP-2 promotes directed intravascular leukocyte migration through platelet thrombi. Blood. 2013;121:4555–66.CrossRefPubMedPubMedCentral
71.
Yang D, Chen Q, Hoover DM, Staley P, Tucker KD, Lubkowski J, Oppenheim JJ. Many chemokines including CCL20/MIP-3alpha display antimicrobial activity. J Leukoc Biol. 2003;74:448–55.CrossRefPubMed
72.
Kochanek PM, Hallenbeck JM. Polymorphonuclear leukocytes and monocytes/macrophages in the pathogenesis of cerebral ischemia and stroke. Stroke. 1992;23:1367–79.CrossRefPubMed
73.
Bielecki B, Jatczak-Pawlik I, Wolinski P, Bednarek A, Glabinski A. Central nervous system and peripheral expression of CCL19, CCL21 and their receptor CCR7 in experimental model of multiple sclerosis. Arch Immunol Ther Exp (Warsz). 2015;63:367–76.CrossRef
74.
Zaremba J, Ilkowski J, Losy J. Serial measurements of levels of the chemokines CCL2, CCL3 and CCL5 in serum of patients with acute ischaemic stroke. Folia Neuropathol. 2006;44:282–9.PubMed
75.
Yu X, Li H, Ren X. Interaction between regulatory T cells and cancer stem cells. Int J Cancer. 2012;131:1491–8.CrossRefPubMed
76.
Okamura H, Tsutsui H, Kashiwamura S, Yoshimoto T, Nakanishi K. Interleukin-18: a novel cytokine that augments both innate and acquired immunity. Adv Immunol. 1998;70:281–312.CrossRefPubMed
77.
Mathy NL, Scheuer W, Lanzendorfer M, Honold K, Ambrosius D, Norley S, Kurth R. Interleukin-16 stimulates the expression and production of pro-inflammatory cytokines by human monocytes. Immunology. 2000;100:63–9.CrossRefPubMedPubMedCentral
78.
79.
80.
Deola S, Panelli MC, Maric D, Selleri S, Dmitrieva NI, Voss CY, Klein H, Stroncek D, Wang E, Marincola FM. Helper B cells promote cytotoxic T cell survival and proliferation independently of antigen presentation through CD27/CD70 interactions. J Immunol. 2008;180:1362–72.CrossRefPubMed
81.
82.
Bis JC, Heckbert SR, Smith NL, Reiner AP, Rice K, Lumley T, Hindorff LA, Marciante KD, Enquobahrie DA, Monks SA, et al. Variation in inflammation-related genes and risk of incident nonfatal myocardial infarction or ischemic stroke. Atherosclerosis. 2008;198:166–73.CrossRefPubMed
83.
Shimamura M, Nakagami H, Osako MK, Kurinami H, Koriyama H, Zhengda P, Tomioka H, Tenma A, Wakayama K, Morishita R. OPG/RANKL/RANK axis is a critical inflammatory signaling system in ischemic brain in mice. Proc Natl Acad Sci U S A. 2014;111:8191–6.CrossRefPubMedPubMedCentral
84.
Inacio AR, Ruscher K, Leng L, Bucala R, Deierborg T. Macrophage migration inhibitory factor promotes cell death and aggravates neurologic deficits after experimental stroke. J Cereb Blood Flow Metab. 2011;31:1093–106.CrossRefPubMed
85.
Wang Y, Chang CF, Morales M, Chou J, Chen HL, Chiang YH, Lin SZ, Cadet JL, Deng X, Wang JY, et al. Bone morphogenetic protein-6 reduces ischemia-induced brain damage in rats. Stroke. 2001;32:2170–8.CrossRefPubMed
86.
Liu Y, Belayev L, Zhao W, Busto R, Saul I, Alonso O, Ginsberg MD. The effect of bone morphogenetic protein-7 (BMP-7) on functional recovery, local cerebral glucose utilization and blood flow after transient focal cerebral ischemia in rats. Brain Res. 2001;905:81–90.CrossRefPubMed
87.
Chou J, Harvey BK, Chang CF, Shen H, Morales M, Wang Y. Neuroregenerative effects of BMP7 after stroke in rats. J Neurol Sci. 2006;240:21–9.CrossRefPubMed
88.
Gurney ME, Heinrich SP, Lee MR, Yin HS. Molecular cloning and expression of neuroleukin, a neurotrophic factor for spinal and sensory neurons. Science. 1986;234:566–74.CrossRefPubMed
89.
90.
91.
Yu Y, Zhang ZH, Wei SG, Chu Y, Weiss RM, Heistad DD, Felder RB. Central gene transfer of interleukin-10 reduces hypothalamic inflammation and evidence of heart failure in rats after myocardial infarction. Circ Res. 2007;101:304–12.CrossRefPubMed
92.
Pestka S, Krause CD, Sarkar D, Walter MR, Shi Y, Fisher PB. Interleukin-10 and related cytokines and receptors. Annu Rev Immunol. 2004;22:929–79.CrossRefPubMed
Metadata
Title
Exercise attenuates neurological deficits by stimulating a critical HSP70/NF-κB/IL-6/synapsin I axis in traumatic brain injury rats
Authors
Chung-Ching Chio
Hung-Jung Lin
Yu-Feng Tian
Yu-Chieh Chen
Mao-Tsun Lin
Cheng-Hsien Lin
Ching-Ping Chang
Chien-Chin Hsu
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2017
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-017-0867-9

Other articles of this Issue 1/2017

Journal of Neuroinflammation 1/2017 Go to the issue

Research

Everolimus is better than rapamycin in attenuating neuroinflammation in kainic acid-induced seizures

Research

Inhibiting the microglia activation improves the spatial memory and adult neurogenesis in rat hippocampus during 48 h of sleep deprivation

Research

The Carbon monoxide releasing molecule ALF-186 mediates anti-inflammatory and neuroprotective effects via the soluble guanylate cyclase ß1 in rats’ retinal ganglion cells after ischemia and reperfusion injury

Research

Regulatory role of cytosolic phospholipase A2 alpha in the induction of CD40 in microglia

Review

Novel pathomechanisms in inflammatory neuropathies

Research

EZH2 suppression in glioblastoma shifts microglia toward M1 phenotype in tumor microenvironment