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Divergent Roles for Tumor Necrosis Factor-α in the Brain

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Abstract

Proinflammatory cytokines and chemokines have been implicated in the pathogenesis of several neurological and neurodegenerative disorders. Prominent among such factors is the pleiotropic cytokine, tumor necrosis factor (TNF)-α. Under normal physiological conditions, TNF-α orchestrates a diverse array of functions involved in immune surveillance and defense, cellular homeostasis, and protection against certain neurological insults. However, paradoxical effects of this cytokine have been observed. TNF-α is elicited in the brain following injury (ischemia, trauma), infection (HIV, meningitis), neurodegeneration (Alzheimer’s, Parkinson’s), and chemically induced neurotoxicity. The multifarious identity for this cytokine appears to be influenced by several mechanisms. Among the most prominent are the regulation of TNFα-induced NF-κB activation by adapter proteins such as TRADD and TRAF, and second, the heterogeneity of microglia and their distribution pattern across brain regions. Here, we review the differential role of TNF-α in response to brain injury, with emphasis on neurodegeneration, and discuss the possible mechanisms for such diverse and region-specific effects.

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Abbreviations

3-NP:

3-nitropropionic acid

6-OHDA:

6-hydroxydopamine

Aβ:

amyloid beta peptide

AD:

Alzheimer’s disease

BBB:

blood–brain barrier

Bcl2:

B-cell CLL/lymphoma 2

BCSFB:

blood–cerebrospinal fluid barrier

BRE:

brain and reproductive organ expressed gene

CER:

cerebellum

CNS:

central nervous system

CSF:

cerebrospinal fluid

CTX:

cortex

DD:

death domain

DENN:

differentially expressed in normal versus neoplastic

EAE:

experimental allergic encephalomyelitis

FADD:

Fas-associated death domain

HIP:

Hippocampus

HIV:

human immunodeficiency virus

MADD:

mitogen-activated protein kinase-activating death domain

MCAO:

middle cerebral artery occlusion

MDMA:

3,4-methylenedioxymethamphetamine

METH:

methamphetamine

MHC:

major histocompatibility complex

MK-801:

(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate

MnSOD:

manganese superoxide dismutase

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

MS:

multiple sclerosis

NFκB:

nuclear factor kappa B

NIK:

nuclear factor kappa B inducing kinase

NMDA:

N-methyl-d-aspartic acid

PD:

Parkinson’s disease

RIP:

receptor-interacting protein

TACE:

TNF-α converting enzyme

TNF:

tumor necrosis factor

TNFR:

tumor necrosis factor receptor

TNFR-DKO:

tumor necrosis factor receptor double knockout

TRADD:

TNF receptor-associated death domain

TRAF:

TNF receptor-associated factor

TRIP:

TRAF-interacting protein

References

  • Achim CL, Heyes MP, Wiley CA (1993) Quantitation of human immunodeficiency virus, immune activation factors, and quinolinic acid in AIDS brains. J Clin Invest 91:2769–2775

    Article  PubMed  CAS  Google Scholar 

  • Aggarwal BB (2003) Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol 3:745–756

    PubMed  CAS  Google Scholar 

  • Ajtai BM, Kalman M (1998) Glial fibrillary acidic protein expression but no glial demarcation follows the lesion in the molecular layer of cerebellum. Brain Res 802:285–288

    PubMed  CAS  Google Scholar 

  • Akassoglou K, Douni E, Bauer J, Lassmann H, Kollias G, Probert L (2003) Exclusive tumor necrosis factor (TNF) signaling by the p75TNF receptor triggers inflammatory ischemia in the CNS of transgenic mice. Proc Natl Acad Sci USA 100:709–714

    PubMed  CAS  Google Scholar 

  • Albensi BC, Mattson MP (2000) Evidence for the involvement of TNF and NF-kappaB in hippocampal synaptic plasticity. Synapse 35:151–159

    PubMed  CAS  Google Scholar 

  • Aloisi F (2001) Immune function of microglia. Glia 36:165–179

    PubMed  CAS  Google Scholar 

  • Aoki T, Kobayashi K, Isaki K (1999) Microglial and astrocytic change in brains of Creutzfeldt–Jakob disease: an immunocytochemical and quantitative study. Clin Neuropathol 18:51–60

    PubMed  CAS  Google Scholar 

  • Arimoto T, Bing G (2003) Up-regulation of inducible nitric oxide synthase in the substantia nigra by lipopolysaccharide causes microglial activation and neurodegeneration. Neurobiol Dis 12:35–45

    PubMed  CAS  Google Scholar 

  • Asanuma M, Tsuji T, Miyazaki I, Miyoshi K, Ogawa N (2003) Methamphetamine-induced neurotoxicity in mouse brain is attenuated by ketoprofen, a non-steroidal anti-inflammatory drug. Neurosci Lett 352:13–16

    PubMed  CAS  Google Scholar 

  • Banati RB, Daniel SF, Blunt SB (1998) Glial pathology but absence of apoptotic nigral neurons in long-standing Parkinson’s disease. Mov Disord 13:221–227

    PubMed  CAS  Google Scholar 

  • Barger SW, Horster D, Furukawa K, Goodman Y, Krieglstein J, Mattson MP (1995) Tumor necrosis factors alpha and beta protect neurons against amyloid beta-peptide toxicity: evidence for involvement of a kappa B-binding factor and attenuation of peroxide and Ca2+ accumulation. Proc Natl Acad Sci U S A 92:9328–9332

    PubMed  CAS  Google Scholar 

  • Barone FC, Arvin B, White RF, Miller A, Webb CL, Willette RN, Lysko PG, Feuerstein GZ (1997) Tumor necrosis factor-alpha. A mediator of focal ischemic brain injury. Stroke 28:1233–1244

    PubMed  CAS  Google Scholar 

  • Benkovic SA, O’Callaghan JP, Miller DB (2004) Sensitive indicators of injury reveal hippocampal damage in C57BL/6J mice treated with kainic acid in the absence of tonic–clonic seizures. Brain Res 1024:59–76

    PubMed  CAS  Google Scholar 

  • Benkovic SA, O’Callaghan JP, Miller DB (2006) Regional neuropathology following kainic acid intoxication in adult and aged C57BL/6J mice. Brain Res 1070:215–231

    PubMed  CAS  Google Scholar 

  • Benveniste EN, Sparacio SM, Bethea JR (1989) Tumor necrosis factor-alpha enhances interferon-gamma-mediated class II antigen expression on astrocytes. J Neuroimmunol 25:209–219

    PubMed  CAS  Google Scholar 

  • Berman J, Carson MJ, Chang L, Cox BM, Fox HS, Gonzalez RG, Hanson GR, Hauser KF, Ho W-Z, Maragos WF, Masliah E, McArthur JC, Miller DB, Nath A, O’Callaghan JP, Persidsky Y, Power C, Rogers TJ, Royal W (2006) NeuroAIDS, drug abuse and inflammation: building collaborative research activities. J Neuroimmune Pharmacol 1:351–399

    Google Scholar 

  • Bizette C, Chan-Chi-Song P, Fontaine M, Tadie M (1996) Expression of mRNA, interleukin-1 beta, interleukin 6 and tumor necrosis factor-alpha during regeneration of the sciatic nerve in rats after tissue loss. Chirurg 121:474–481

    CAS  Google Scholar 

  • Block F, Schmidt W, Nolden-Koch M, Schwarz M (2001) Rolipram reduces excitotoxic neuronal damage. NeuroReport 12:1507–1511

    PubMed  CAS  Google Scholar 

  • Bogdan I, Leib SL, Bergeron M, Chow L, Tauber MG (1997) Tumor necrosis factor-alpha contributes to apoptosis in hippocampal neurons during experimental group B streptococcal meningitis. J Infect Dis 176:693–697

    PubMed  CAS  Google Scholar 

  • Boka G, Anglade P, Wallach D, Javoy-Agid F, Agid Y, Hirsch EC (1994) Immunocytochemical analysis of tumor necrosis factor and its receptors in Parkinson’s disease. Neurosci Lett 172:151–154

    PubMed  CAS  Google Scholar 

  • Botchkina GI, Meistrell ME 3rd, Botchkina IL, Tracey KJ (1997) Expression of TNF and TNF receptors (p55 and p75) in the rat brain after focal cerebral ischemia. Mol Med 3:765–781

    PubMed  CAS  Google Scholar 

  • Botchkina GI, Geimonen E, Bilof ML, Villarreal O, Tracey KJ (1999) Loss of NF-kappaB activity during cerebral ischemia and TNF cytotoxicity. Mol Med 5:372–381

    PubMed  CAS  Google Scholar 

  • Brabers NA, Nottet HS (2006) Role of the pro-inflammatory cytokines TNF-alpha and IL-1beta in HIV-associated dementia. Eur J Clin Invest 36:447–458

    PubMed  CAS  Google Scholar 

  • Bruce AJ, Boling W, Kindy MS, Peschon J, Kraener PJ, Carpenter MK, Holtsberg FW, Mattson MP (1996) Altered neuronal and microglial responses to excitotoxic and ischemic brain injury in mice lacking TNF receptors. Nat Med 2:788–794

    PubMed  CAS  Google Scholar 

  • Bruce-Keller AJ, Geddes JW, Knapp PE, McFall RW, Keller JN, Holtsberg FW, Parthasarathy S, Steiner SM, Mattson MP (1999) Anti-death properties of TNF against metabolic poisoning: mitochondrial stabilization by MnSOD. J Neuroimmunol 93:53–71

    PubMed  CAS  Google Scholar 

  • Bruunsgaard H, Andersen-Ranberg K, Jeune B, Pedersen AN, Skinhoj P, Pedersen BK (1999) A high plasma concentration of TNF-alpha is associated with dementia in centenarians. J Gerontol Ser A Biol Sci Med Sci 54:M357–364

    CAS  Google Scholar 

  • Butler TL, Kassed CA, Sanberg PR, Willing AE, Pennypacker KR (2002) Neurodegeneration in the rat hippocampus and striatum after middle cerebral artery occlusion. Brain Res 929:252–260

    PubMed  CAS  Google Scholar 

  • Buttini M, Appel K, Sauter A, Gebicke-Haerter PJ, Boddeke HW (1996) Expression of tumor necrosis factor alpha after focal cerebral ischaemia in the rat. Neuroscience 71:1–16

    PubMed  CAS  Google Scholar 

  • Cannella B, Raine CS (1995) The adhesion molecule and cytokine profile of multiple sclerosis lesions. Ann Neurol 37:424–435

    PubMed  CAS  Google Scholar 

  • Carbonell WS, Mandell JW (2003) Transient neuronal but persistent astroglial activation of ERK/MAP kinase after focal brain injury in mice. J Neurotrauma 20:327–336

    PubMed  Google Scholar 

  • Cardenas H, Bolin LM (2003) Compromised reactive microgliosis in MPTP-lesioned IL-6 KO mice. Brain Res 985:89–97

    PubMed  CAS  Google Scholar 

  • Carlson NG, Bacchi A, Rogers SW, Gahring LC (1998) Nicotine blocks TNF-alpha-mediated neuroprotection to NMDA by an alpha-bungarotoxin-sensitive pathway. J Neurobiol 35:29–36

    PubMed  CAS  Google Scholar 

  • Carson MJ, Doose JM, Melchior B, Schmid CD, Ploix CC (2006) CNS immune privilege: hiding in plain sight. Immunol Rev 213:48–65

    PubMed  Google Scholar 

  • Chao CC, Hu S (1994) Tumor necrosis factor-alpha potentiates glutamate neurotoxicity in human fetal brain cell cultures. Dev Neurosci 16:172–179

    PubMed  CAS  Google Scholar 

  • Cheng B, Christakos S, Mattson MP (1994) Tumor necrosis factors protect neurons against metabolic–excitotoxic insults and promote maintenance of calcium homeostasis. Neuron 12:139–153

    PubMed  CAS  Google Scholar 

  • Cheung WM, Wang CK, Kuo JS, Lin TN (1999) Changes in the level of glial fibrillary acidic protein (GFAP) after mild and severe focal cerebral ischemia. Chin J Physiol 42:227–235

    PubMed  CAS  Google Scholar 

  • Christov A, Ottman JT, Grammas P (2004) Vascular inflammatory, oxidative and protease-based processes: implications for neuronal cell death in Alzheimer’s disease. Neurol Res 26:540–546

    PubMed  CAS  Google Scholar 

  • Chung SY, Han SH (2003) Melatonin attenuates kainic acid-induced hippocampal neurodegeneration and oxidative stress through microglial inhibition. J Pineal Res 34:95–102

    PubMed  CAS  Google Scholar 

  • Collins JS, Perry RT, Watson B Jr, Harrell LE, Acton RT, Blacker D, Albert MS, Tanzi RE, Bassett SS, McInnis MG, Campbell RD, Go RC (2000) Association of a haplotype for tumor necrosis factor in siblings with late-onset Alzheimer disease: the NIMH Alzheimer Disease Genetics Initiative. Am J Med Genet 96:823–830

    PubMed  CAS  Google Scholar 

  • Dawson DA, Martin D, Hallenbeck JM (1996) Inhibition of tumor necrosis factor-alpha reduces focal cerebral ischemic injury in the spontaneously hypertensive rat. Neurosci Lett 218:41–44

    PubMed  CAS  Google Scholar 

  • De Bock F, Dornand J, Rondouin G (1996) Release of TNF alpha in the rat hippocampus following epileptic seizures and excitotoxic neuronal damage. NeuroReport 7:1125–1129

    PubMed  Google Scholar 

  • Declercq W, Denecker G, Fiers W, Vandenabeele P (1998) Cooperation of both TNF receptors in inducing apoptosis: involvement of the TNF receptor-associated factor binding domain of the TNF receptor 75. J Immunol 161:390–399

    PubMed  CAS  Google Scholar 

  • Depino AM, Earl C, Kaczmarczyk E, Ferrari C, Bededovsky H, del Rey A, Pitossi FJ, Oertel WH (2003) Microglial activation with atypical proinflammatory cytokine expression in a rat model of Parkinson’s disease. Eur J Neurosci 18:2731–2742

    PubMed  Google Scholar 

  • Dickson DW, Lee SC, Mattiace LA, Yen SH, Brosnan C (1993) Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer’s disease. Glia 7:75–83

    PubMed  CAS  Google Scholar 

  • Dihne M, Block F (2001) Focal ischemia induces transient expression of IL-6 in the substantia nigra pars reticulata. Brain Res 889:165–173

    PubMed  CAS  Google Scholar 

  • Dihne M, Block F, Korr H, Topper R (2001) Time course of glial proliferation and glial apoptosis following excitotoxic CNS injury. Brain Res 902:178–189

    PubMed  CAS  Google Scholar 

  • Dobbs RJ, Charlett A, Purkiss AG, Dobbs SM, Weller C, Peterson DW (1999) Association of circulating TNF-alpha and IL-6 with ageing and parkinsonism. Acta Neurol Scand 100:34–41

    PubMed  CAS  Google Scholar 

  • Dopp JM, Mackenzie-Graham A, Otero GC, Merrill JE (1997) Differential expression, cytokine modulation, and specific functions of type-1 and type-2 tumor necrosis factor receptors in rat glia. J Neuroimmunol 75:104–112

    PubMed  CAS  Google Scholar 

  • Dziewulska D, Mossakowski MJ (2003) Cellular expression of tumor necrosis factor α and its receptors in human ischemic stroke. Clin Neuropathol 22:35–40

    PubMed  CAS  Google Scholar 

  • Eikelenboom P, Rozemuller AJ, Hoozemans JJ, Veerhuis R, van Gool WA (2000) Neuroinflammation and Alzheimer disease: clinical and therapeutic implications. Alzheimer Dis Assoc Disord 14(Suppl 1):S54–61

    PubMed  CAS  Google Scholar 

  • Engel S, Wehner HD, Meyermann R (1996) Expression of microglial markers in the human CNS after closed head injury. Acta Neurochir Suppl (Wien) 66:89–95

    CAS  Google Scholar 

  • Engelhardt B (2006) Regulation of immune cell entry into the central nervous system. Results Probl Cell Differ 43:259–280

    Article  PubMed  CAS  Google Scholar 

  • Fan L, Young PR, Barone FC, Feuerstein GZ, Smith DH, McIntosh TK (1996) Experimental brain injury induces differential expression of tumor necrosis factor-alpha mRNA in the CNS. Brain Res Mol Brain Res 36:287–291

    PubMed  CAS  Google Scholar 

  • Ferger B, Leng A, Mura A, Hengerer B, Feldon J (2004) Genetic ablation of tumor necrosis factor-alpha (TNF-alpha) and pharmacological inhibition of TNF-synthesis attenuates MPTP toxicity in mouse striatum. J Neurochem 89:822–833

    PubMed  CAS  Google Scholar 

  • Fiedorowicz A, Figiel I, Kaminska B, Zaremba M, Wilk S, Oderfeld-Nowak B (2001) Dentate granule neuron apoptosis and glia activation in murine hippocampus induced by trimethyltin exposure. Brain Res 912:116–127

    PubMed  CAS  Google Scholar 

  • Flora G, Lee YW, Nath A, Maragos W, Hennig B, Toborek M (2002) Methamphetamine-induced TNF-alpha gene expression and activation of AP-1 in discrete regions of mouse brain: potential role of reactive oxygen intermediates and lipid peroxidation. Neuromolecular Med 2:71–85

    PubMed  CAS  Google Scholar 

  • Fontaine V, Mohand-Said S, Hanoteau N, Fuchs C, Pfizenmaier K, Eisel U (2002) Neurodegenerative and neuroprotective effects of tumor necrosis factor (TNF) in retinal ischemia: opposite roles of TNF receptor 1 and TNF receptor 2. J Neurosci 22:RC216

    PubMed  Google Scholar 

  • Francis JW, Von Visger J, Markelonis GJ, Oh TH (1995) Neuroglial responses to the dopaminergic neurotoxicant, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mouse striatum. Neurotoxicol Teratol 17:7–12

    PubMed  CAS  Google Scholar 

  • Galasso JM, Wang P, Martin D, Silverstein FS (2000) Inhibition of TNF-alpha can attenuate or exacerbate excitotoxic injury in neonatal rat brain. NeuroReport 7:231–235

    Article  Google Scholar 

  • Gartner S, Liu Y (2002) Insights into the role of immune activation in HIV neuropathogenesis. J Neurovirol 8:69–75

    PubMed  CAS  Google Scholar 

  • Gary DS, Bruce-Keller AJ, Kindy MS, Mattson MP (1998) Ischemic and excitotoxic brain injury is enhanced in mice lacking the p55 tumor necrosis factor receptor. J Cereb Blood Flow Metab 18:1283–1287

    PubMed  CAS  Google Scholar 

  • Gerber J, Bottcher T, Hahn M, Siemer A, Bunkowski S, Nau R (2004) Increased mortality and spatial memory deficits in TNF-alpha-deficient mice in ceftriaxone-treated experimental pneumococcal meningitis. Neurobiol Dis 16:133–138

    PubMed  CAS  Google Scholar 

  • Gianinazzi C, Grandgirard D, Imboden H, Egger L, Meli DN, Bifrare YD, Joss PC, Tauber MG, Borner C, Leib SL (2003) Caspase-3 mediates hippocampal apoptosis in pneumococcal meningitis. Acta Neuropathol (Berl) 105:499–507

    CAS  Google Scholar 

  • Ginis I, Jaiswal R, Klimanis D, Liu J, Greenspon J, Hallenbeck JM (2002) TNF-alpha-induced tolerance to ischemic injury involves differential control of NF-kappaB transactivation: the role of NF-kappaB association with p300 adaptor. J Cereb Blood Flow Metab 22:142–152

    PubMed  CAS  Google Scholar 

  • Gonzalez-Scarano F, Baltuch G (1999) Microglia as mediators of inflammatory and degenerative diseases. Annu Rev Neurosci 22:219–240

    PubMed  CAS  Google Scholar 

  • Goodman Y, Mattson MP (1996) Ceramide protects hippocampal neurons against excitotoxic and oxidative insults, and amyloid beta-peptide toxicity. J Neurochem 66:869–872

    Article  PubMed  CAS  Google Scholar 

  • Goodman JC, Robertson CS, Grossman RG, Narayan RK (1990) Elevation of tumor necrosis factor in head injury. J Neuroimmunol 30:213–217

    PubMed  CAS  Google Scholar 

  • Grassi F, Mileo AM, Monaco L, Punturieri A, Santoni A, Eusebi F (1994) TNF-alpha increases the frequency of spontaneous miniature synaptic currents in cultured rat hippocampal neurons. Brain Res 659:226–230

    PubMed  CAS  Google Scholar 

  • Gray F, Chretien F, Adle-Biassette H, Dorandeu A, Ereau T, Delisle MB, Kopp N, Ironside JW, Vital C (1999) Neuronal apoptosis in Creutzfeldt-Jakob disease. J Neuropathol Exp Neurol 58:321–328

    PubMed  CAS  Google Scholar 

  • Gu C, Castellino A, Chan JY, Chao MV (1998) BRE: a modulator of TNF-alpha action. FASEB J 12:1101–1108

    PubMed  CAS  Google Scholar 

  • Hauser SL, Doolittle TH, Lincoln R, Brown RH, Dinarello CA (1990) Cytokine accumulations in CSF of multiple sclerosis patients: frequent detection of interleukin-1 and tumor necrosis factor but not interleukin-6. Neurology 40:1735–1739

    PubMed  CAS  Google Scholar 

  • Hehlgans T, Pfeffer K (2005) The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games. Immunology 115:1–20

    PubMed  CAS  Google Scholar 

  • Hirsch EC, Breidert T, Rousselet E, Hunot S, Hartmann A, Michel PP (2003) The role of glial reaction and inflammation in Parkinson’s disease. Ann NY Acad Sci 991:214–228

    Article  PubMed  CAS  Google Scholar 

  • Holmin S, Schalling M, Hojeberg B, Nordqvist AC, Skeftruna AK, Mathiesen T (1997) Delayed cytokine expression in rat brain following experimental contusion. J Neurosurg 86:493–504

    Article  PubMed  CAS  Google Scholar 

  • Houzen H, Kikuchi S, Kanno M, Shinpo K, Tashiro K (1997) Tumor necrosis factor enhancement of transient outward potassium currents in cultured rat cortical neurons. J Neurosci Res 50:990–999

    PubMed  CAS  Google Scholar 

  • Hsu H, Shu HB, Pan MG, Goeddel DV (1996) TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 84:299–308

    PubMed  CAS  Google Scholar 

  • Intiso D, Zarrelli MM, Lagioia G, Di Rienzo F, Checchia De Ambrosio C, Simone P, Tonali P, Cioffi Dagger RP (2004) Tumor necrosis factor alpha serum levels and inflammatory response in acute ischemic stroke patients. Neurol Sci 24:390–396

    PubMed  CAS  Google Scholar 

  • Isono M, Goda M, Kobayashi H, Wu JL (2003) TGF-alpha over-expression induces astrocytic hypertrophy after cortical stab would injury. Neurol Res 25:546–550

    PubMed  CAS  Google Scholar 

  • Janelsins MC, Mastrangelo MA, Oddo S, LaFerla FM, Federoff HJ, Bowers WJ (2005) Early correlation of microglial activation with enhanced tumor necrosis factor-alpha and monocyte chemoattractant protein-1 expression specifically within the entorhinal cortex of triple transgenic Alzheimer’s disease mice. J Neuroinflammation 2:23

    PubMed  Google Scholar 

  • Johnson EA, O’Callaghan JP, Miller DB (2002) Chronic treatment with supraphysiological levels of corticosterone enhances D-MDMA-induced dopaminergic neurotoxicity in the C57BL/6J female mouse. Brain Res 933:130–138

    PubMed  CAS  Google Scholar 

  • Joseph SA, Tassorelli C, Prasad AV, Lynd-Balta E (1996) NF-kappa B transcription factor subunits in rat brain: colocalization of p65 and alpha-MSH. Peptides 17:655–664

    PubMed  CAS  Google Scholar 

  • Kaltschmidt B, Uherek M, Wellmann H, Volk B, Kaltschmidt C (1999) Inhibition of NF-kappaB potentiates amyloid beta-mediated neuronal apoptosis. Proc Natl Acad Sci USA 96:9409–9414

    PubMed  CAS  Google Scholar 

  • Katchanov J, Waeber C, Gertz K, Gietz A, Winter B, Bruck W, Dirnagl U, Veh RW, Endres M (2003) Selective neuronal vulnerability following mild focal brain ischemia in the mouse. Brain Pathol 13:452–464

    Article  PubMed  Google Scholar 

  • Kita T, Liu L, Tanaka N, Kinoshita Y (1997) The expression of tumor necrosis factor-alpha in the rat brain after fluid percussive injury. Int J Legal Med 110:305–311

    PubMed  CAS  Google Scholar 

  • Knoblach SM, Fan L, Faden AI (1999) Early neuronal expression of tumor necrosis factor-alpha after experimental brain injury contributes to neurological impairment. J Neuroimmunol 95:115–125

    PubMed  CAS  Google Scholar 

  • Koller H (1997) TNF alpha in cerebrospinal fluid of meningitis patients reduces astrocytes membrane potential. J Neuroimmunol 76:185–188

    PubMed  CAS  Google Scholar 

  • Kreutzberg GW (1996) Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19:312–318

    PubMed  CAS  Google Scholar 

  • Krum JM, Phillips TM, Rosenstein JM (2002) Changes in astroglial GLT-1 expression after neural transplantation or stab wounds. Exp Neurol 174:137–149

    PubMed  CAS  Google Scholar 

  • Laskawi R, Rohlmann A, Landgrebe M, Wolff JR (1997) Rapid astroglial reactions in the motor cortex of adult rats following peripheral facial nerve lesions. Eur Arch Otorhinolaryngol 254:81–85

    PubMed  CAS  Google Scholar 

  • Lavine SD, Hofman FM, Zlokovic BV (1998) Circulating antibody against tumor necrosis factor-alpha protects rat brain from reperfusion injury. J Cereb Blood Flow Metab 18:52–58

    PubMed  CAS  Google Scholar 

  • Lawson LJ, Perry VH, Dri P, Gordon S (1990) Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience 39:151–170

    PubMed  CAS  Google Scholar 

  • Little AR, Benkovic SA, Miller DB, O’Callaghan JP (2002) Chemically induced neuronal damage and gliosis: enhanced expression of the proinflammatory chemokine, monocyte chemoattractant protein (MCP)-1, without a corresponding increase in proinflammatory cytokines. Neuroscience 115:307–320

    PubMed  CAS  Google Scholar 

  • Liu T, Clark RK, McDonnell PC, Young PR, White RF, Barone FC, Feuerstein GZ (1994) Tumor necrosis factor-alpha expression in ischemic neurons. Stroke 25:1481–1488

    PubMed  CAS  Google Scholar 

  • Liu XH, Xu H, Barks JD (1999) Tumor necrosis factor-α attenuates N-methyl-d-aspartate-mediated neurotoxicity in neonatal rat hippocampus. Brain Res 851:94–104

    PubMed  CAS  Google Scholar 

  • Lucas R, Juillard P, Decoster E, Redard M, Burger D, Donati Y, Giroud C, Monso-Hinard C, De Kesel T, Buurman WA, Moore MW, Dayer JM, Fiers W, Bluethmann H, Grau GE (1997) Crucial role of tumor necrosis factor (TNF) receptor 2 and membrane-bound TNF in experimental cerebral malaria. Eur J Immunol 27:1719–1725

    PubMed  CAS  Google Scholar 

  • Manchester M, Eto DS, Oldstone MB (1999) Characterization of the inflammatory response during acute measles encephalitis in NSE-CD46 transgenic mice. J Neuroimmunol 96:207–217

    PubMed  CAS  Google Scholar 

  • Marquette C, Van Dam AM, Ceccaldi PE, Weber P, Haour F, Tsiang H (1996) Induction of immunoreactive interleukin-1 beta and tumor necrosis factor-alpha in the brains of rabies virus infected rats. J Neuroimmunol 68:45–51

    PubMed  CAS  Google Scholar 

  • Martino G, Consiglio A, Franciotta DM, Corti A, Filippi M, Vandenbroeck K, Sciacca FL, Comi G, Grimaldi LM (1997) Tumor necrosis factor alpha and its receptors in relapsing-remitting multiple sclerosis. J Neurol Sci 152:51–61

    PubMed  CAS  Google Scholar 

  • Masliah E, LiCastro F (2000) Neuronal and synaptic loss, reactive gliosis, microglial response, and induction of the complement cascade in Alzheimer’s disease. In: Clark CM, Trojanowski, JQ (eds) Neurodegenerative dementias, McGraw-Hill, New York, pp. 131–146

    Google Scholar 

  • Mattson MP, Cheng B, Baldwin SA, Smith-Swintosky VL, Keller J, Geddes JW, Scheff SW, Christakos S (1995) Brain injury and tumor necrosis factors induce calbindin D-28k in astrocytes: evidence for a cytoprotective response. J Neurosci Res 42:357–370

    PubMed  CAS  Google Scholar 

  • Mattson MP, Goodman Y, Luo H, Fu W, Furukawa K (1997) Activation of NF-kappaB protects hippocampal neurons against oxidative stress-induced apoptosis: evidence for induction of manganese superoxide dismutase and suppression of peroxynitrite production and protein tyrosine nitration. J Neurosci Res 49:681–697

    PubMed  CAS  Google Scholar 

  • Matusevicius D, Navikas V, Soderstrom M, Xiao BG, Haglund M, Fredrikson S, Link H (1996) Multiple sclerosis: the proinflammatory cytokines lymphotoxin-alpha and tumour necrosis factor-alpha are upregulated in cerebrospinal fluid mononuclear cells. J Neuroimmunol 66:115–123

    PubMed  CAS  Google Scholar 

  • McCoy MK, Martinez TN, Ruhn KA, Szymkowski DE, Smith CG, Botterman BR, Tansey KE, Tansey MG (2006) Blocking soluble tumor necrosis factor signaling with dominant-negative tumor necrosis factor inhibitor attenuates loss of dopaminergic neurons in models of Parkinson’s disease. J Neurosci 26:9365–9375

    PubMed  CAS  Google Scholar 

  • McGeer PL, McGeer EG (1998) Glial cell reactions in neurodegenerative diseases: pathophysiology and therapeutic interventions. Alzheimer Dis Assoc Disord 12(Suppl 2):S1–S6

    PubMed  CAS  Google Scholar 

  • McGeer PL, McGeer EG (2004) Inflammation and the degenerative diseases of aging. Ann N Y Acad Sci 1035:104–116

    PubMed  CAS  Google Scholar 

  • McGeer PL, Schwab C, Parent A, Doudet D (2003) Presence of reactive microglia in monkey substantia nigra years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration. Ann Neurol 54:599–604

    PubMed  CAS  Google Scholar 

  • Meda L, Cassatella MA, Szendrei GI, Otvos L Jr, Baron P, Villalba M, Ferrari D, Rossi F (1995) Activation of microglial cells by beta-amyloid protein and interferon-gamma. Nature 374:647–650

    PubMed  CAS  Google Scholar 

  • Meistrell ME 3rd, Botchkina GI, Wang H, Di Santo E, Cockroft KM, Bloom O, Vishnubhakat JM, Ghezzi P, Tracey KJ (1997) Tumor necrosis factor is a brain damaging cytokine in cerebral ischemia. Shock 8:341–348

    PubMed  Google Scholar 

  • Minghetti L (2005) Role of inflammation in neurodegenerative diseases. Curr Opin Neurol 18:315–321

    PubMed  CAS  Google Scholar 

  • Mogi M, Harada M, Riederer P, Narabayashi H, Fujita K, Nagatsu T (1994) Tumor necrosis factor-alpha increases both in brain and in the cerebrospinal fluid from parkinsonian patients. Neurosci Lett 165:208–210

    PubMed  CAS  Google Scholar 

  • Mogi M, Harada M, Kondo T, Riederer P, Nagatsu T (1995) Brain beta 2-macroglobulin levels are elevated in the striatum in Parkinson’s disease. J Neural Transm 9:87–92

    CAS  Google Scholar 

  • Mogi M, Togari A, Tanaka K, Ogawa N, Ichinose H, Nagatsu T (1999) Increase in level of tumor necrosis factor (TNF)-alpha in 6-hydroxydopamine-lesioned striatum in rats without the influence of systemic L-DOPA on the TNF-alpha induction. Neurosci Lett 268:101–104

    PubMed  CAS  Google Scholar 

  • Munoz-Fernandez MA, Fresno M (1998) The role of tumour necrosis factor, interleukin 6, interferon-gamma and inducible nitric oxide synthase in the development and pathology of the nervous system. Prog Neurobiol 56:307–340

    PubMed  CAS  Google Scholar 

  • Nawashiro H, Tasaki K, Ruetzler CA, Hallenbeck JM (1997) TNF-alpha pretreatment induces protective effects against focal cerebral ischemia in mice. J Cereb Blood Flow Metab 17:483–490

    PubMed  CAS  Google Scholar 

  • Nishimura M, Mizuta I, Mizuta E, Yamasaki S, Ohta M, Kaji R, Kuno S (2001) Tumor necrosis factor gene polymorphisms in patients with sporadic Parkinson’s disease. Neurosci Lett 311:1–4

    PubMed  CAS  Google Scholar 

  • Perry VH (1998) A revised view of the central nervous system microenvironment and major histocompatibility complex class II antigen presentation. J Neuroimmunol 90:113–121

    PubMed  CAS  Google Scholar 

  • Persidsky Y, Limoges J, Rasmussen J, Zheng J, Gearing A, Gendelman HE (2001) Reduction in glial immunity and neuropathology by a PAF antagonist and an MMP and TNFalpha inhibitor in SCID mice with HIV-1 encephalitis. J Neuroimmunol 114:57–68

    PubMed  CAS  Google Scholar 

  • Petzold A, Eikelenboom MJ, Gveric D, Keir G, Chapman M, Lazeron RH, Cuzner ML, Polman CH, Uitdehaag BM, Thompson EJ, Giovannoni G (2002) Markers for different glial cell responses in multiple sclerosis: clinical and pathological correlations. Brain 125:1462–1473

    PubMed  CAS  Google Scholar 

  • Plant SR, Arnett HA, Ting JP (2005) Astroglial-derived lymphotoxin-alpha exacerbates inflammation and demyelination, but not remyelination. Glia 49:1–14

    PubMed  Google Scholar 

  • Probert L, Selmaj K (1997) TNF and related molecules: trends in neuroscience and clinical applications. J Neuroimmunol 72:113–117

    PubMed  CAS  Google Scholar 

  • Quasney MW, Zhang Q, Sargent S, Mynatt M, Glass J, McArthur J (2001) Increased frequency of the tumor necrosis factor-alpha-308 A allele in adults with human immunodeficiency virus dementia. Ann Neurol 50:157–162

    PubMed  CAS  Google Scholar 

  • Quintana A, Giralt M, Rojas S, Penkowa M, Campbell IL, Hidalgo J, Molinero A (2005) Differential role of tumor necrosis factor receptors in mouse brain inflammatory responses in cryolesion brain injury. J Neurosci Res 82:701–716

    PubMed  CAS  Google Scholar 

  • Raivich G, Bluethmann H, Kreutzberg GW (1996) Signaling molecules and neuroglial activation in the injured central nervous system. Keio J Med 45:239–247

    PubMed  CAS  Google Scholar 

  • Ransohoff RM, Glabinski A, Tani M (1996) Chemokines in immune-mediated inflammation of the central nervous system. Cytokine Growth Factor Rev 7:35–46

    PubMed  CAS  Google Scholar 

  • Ren L, Lubrich B, Biber K, Gebicke-Haerter PJ (1999) Differential expression of inflammatory mediators in rat microglia cultured from different brain regions. Brain Res Mol Brain Res 65:198–205

    PubMed  CAS  Google Scholar 

  • Rodrigues RW, Gomide VC, Chadi G (2001) Astroglial and microglial reaction after a partial nigrostriatal degeneration induced by the striatal injection of different doses of 6-hydroxydopamine. Int J Neurosci 109:91–126

    Article  PubMed  CAS  Google Scholar 

  • Rosenberg GA, Estrada EY, Dencoff JE, Stetler-Stevenson WG (1995) Tumor necrosis factor-alpha-induced gelatinase B causes delayed opening of the blood–brain barrier: an expanded therapeutic window. Brain Res 703:151–155

    PubMed  CAS  Google Scholar 

  • Ross SA, Halliday MI, Campbell GC, Byrnes DP, Rowlands BJ (1994) The presence of tumour necrosis factor in CSF and plasma after severe head injury. Br J Neurosurg 8:419–425

    PubMed  CAS  Google Scholar 

  • Ryu JK, Nagai A, Kim J, Lee MC, McLarnon JG, Kim SU (2003) Microglial activation and cell death induced by the mitochondrial toxin 3-nitropropionic acid: in vitro and in vivo studies. Neurobiol Dis 12:121–132

    PubMed  CAS  Google Scholar 

  • Saha RN, Pahan K (2003) Tumor necrosis factor-alpha at the crossroads of neuronal life and death during HIV-associated dementia. J Neurochem 86:1057–1071

    Article  PubMed  CAS  Google Scholar 

  • Sairanen T, Carpen O, Karjalainen-Lindsberg ML, Paetau A, Turpeinen U, Kaste M, Lindsberg PJ (2001) Evolution of cerebral tumor necrosis factor-alpha production during human ischemic stroke. Stroke 32:1750–1758

    PubMed  CAS  Google Scholar 

  • Saito K, Suyama K, Nishida K, Sei Y, Basile AS (1996) Early increases in TNF-alpha, IL-6 and IL-1 beta levels following transient cerebral ischemia in gerbil brain. Neurosci Lett 206:149–152

    PubMed  CAS  Google Scholar 

  • Sanchez-Burgos G, Hernandez-Pando R, Campbell IL, Ramos-Castaneda J, Ramos C (2004) Cytokine production in brain of mice experimentally infected with dengue virus. Neuroreport 15:37–42

    PubMed  CAS  Google Scholar 

  • Schiefer J, Topper R, Schmidt W, Block F, Heinrich PC, Noth J, Schwarz M (1998) Expression of interleukin 6 in the rat striatum following stereotaxic injection of quinolinic acid. J Neuroimmunol 89:168–176

    PubMed  CAS  Google Scholar 

  • Seilhean D, Kobayashi K, He Y, Uchihara T, Rosenblum O, Katlama C, Bricaire F, Duyckaerts C, Hauw JJ (1997) Tumor necrosis factor-alpha, microglia and astrocytes in AIDS dementia complex. Acta Neuropathol (Berl) 93:508–517

    CAS  Google Scholar 

  • Sherer TB, Betarbet R, Kim JH, Greenamyre JT (2003) Selective microglial activation in the rat rotenone model of Parkinson’s disease. Neurosci Lett 341:87–90

    PubMed  CAS  Google Scholar 

  • Shiozaki T, Hayakata T, Tasaki O, Hosotubo H, Fuijita K, Mouri T, Tajima G, Kajino K, Nakae H, Tanaka H, Shimazu T, Sugimoto H (2005) Cerebrospinal fluid concentrations of anti-inflammatory mediators in early-phase severe traumatic brain injury. Shock 23:406–410

    PubMed  CAS  Google Scholar 

  • Shohami E, Novikov M, Bass R, Yamin A, Gallily R (1994) Closed head injury triggers early production of TNF alpha and IL-6 by brain tissue. J Cereb Blood Flow Metab 14:615–619

    PubMed  CAS  Google Scholar 

  • Shohami E, Gallily R, Mechoulam R, Bass R, Ben-Hur T (1997) Cytokine production in the brain following closed head injury: dexanabinol (HU-211) is a novel TNF-alpha inhibitor and an effective neuroprotectant. J Neuroimmunol 72:169–177

    PubMed  CAS  Google Scholar 

  • Shrikant P, Chung IY, Ballestas ME, Benveniste EN (1994) Regulation of intercellular adhesion molecule-1 gene expression by tumor necrosis factor-alpha, interleukin-1 beta, and interferon-gamma in astrocytes. J Neuroimmunol 51:209–220

    PubMed  CAS  Google Scholar 

  • Skias DD, Kim DK, Reder AT, Antel JP, Lancki DW, Fitch FW (1987) Susceptibility of astrocytes to class I MHC antigen-specific cytotoxicity. J Immunol 138:3254–3258

    PubMed  CAS  Google Scholar 

  • Soltys Z, Janeczko K, Orzylowska-Sliwinska O, Zaremba M, Januszewski S, Oderfeld-Nowak B (2003) Morphological transformations of cells immunopositive for GFAP, TrkA or p75 in the CA1 hippocampal area following transient global ischemia in the rat: a quantitative study. Brain Res 987:186–193

    PubMed  CAS  Google Scholar 

  • Sompol P, Xu Y, Ittarat W, Daosukho C, St Clair D (2006) NF-kappaB-associated MnSOD induction protects against beta-amyloid-induced neuronal apoptosis. J Mol Neurosci 29:279–288

    PubMed  CAS  Google Scholar 

  • Sprang SR (1990) The divergent receptors for TNF. Trends Biochem Sci 15:366–368

    PubMed  CAS  Google Scholar 

  • Sriram K, Matheson JM, Benkovic SA, Miller DB, Luster MI, O’Callaghan JP (2002a) Mice deficient in TNF receptors are protected against dopaminergic neurotoxicity: implications for Parkinson’s disease. FASEB J 16:1474–1476

    PubMed  CAS  Google Scholar 

  • Sriram K, Benkovic SA, Miller DB, O’Callaghan JP (2002b) Obesity exacerbates chemically induced neurodegeneration. Neuroscience 115:1335–1346

    PubMed  CAS  Google Scholar 

  • Sriram K, Matheson JM, Benkovic SA, Miller DB, Luster MI, O’Callaghan JP (2006a) Deficiency of TNF receptors suppresses microglial activation and alters the susceptibility of brain regions to MPTP-induced neurotoxicity: role of TNF-α. FASEB J 20:670–682

    PubMed  CAS  Google Scholar 

  • Sriram K, Miller DB, O’Callaghan JP (2006b) Minocycline attenuates microglial activation but fails to mitigate striatal dopaminergic neurotoxicity: role of tumor necrosis factor-α. J Neurochem 93:706–718

    Google Scholar 

  • Stahel PF, Kariya K, Shohami E, Barnum SR, Eugster H, Trentz O, Kossmann T, Morganti-Kossmann MC (2000) Intracerebral complement C5a receptor (CD88) expression is regulated by TNF and lymphotoxin-alpha following closed head injury in mice. J Neuroimmunol 109:164–172

    PubMed  CAS  Google Scholar 

  • Stoll G, Jander S (1999) The role of microglia and macrophages in the pathophysiology of the CNS. Prog Neurobiol 58:233–247

    PubMed  CAS  Google Scholar 

  • Streit WJ, Walter SA, Pennell NA (1999) Reactive microgliosis. Prog Neurobiol 57:563–581

    PubMed  CAS  Google Scholar 

  • Sullivan PG, Bruce-Keller AJ, Rabchevsky AG, Christakos S, Clair DK, Mattson MP, Scheff SW (1999) Exacerbation of damage and altered NF-kappaB activation in mice lacking tumor necrosis factor receptors after traumatic brain injury. J Neurosci 19:6248–6256

    PubMed  CAS  Google Scholar 

  • Tamatani M, Che YH, Matsuzaki H, Ogawa S, Okado H, Miyake S, Mizuno T, Tohyama M (1999) Tumor necrosis factor induces Bcl-2 and Bcl-x expression through NFkappaB activation in primary hippocampal neurons. J Biol Chem 274:8531–8538

    PubMed  CAS  Google Scholar 

  • Tarkowski E, Blennow K, Wallin A, Tarkowski A (1999) Intracerebral production of tumor necrosis factor-alpha, a local neuroprotective agent, in Alzheimer disease and vascular dementia. J Clin Immunol 19:223–230

    PubMed  CAS  Google Scholar 

  • Tartaglia LA, Weber RF, Figari IS, Reynolds C, Palladino MA Jr, Goeddel DV (1991) The two different receptors for tumor necrosis factor mediate distinct cellular responses. Proc Natl Acad Sci USA 88:9292–9296

    PubMed  CAS  Google Scholar 

  • Taupin V, Toulmond S, Serrano A, Benavides J, Zavala F (1993) Increase in IL-6, IL-1 and TNF levels in rat brain following traumatic lesion. Influence of pre- and post-traumatic treatment with Ro5 4864, a peripheral-type (p site) benzodiazepine ligand. J Neuroimmunol 42:177–185

    PubMed  CAS  Google Scholar 

  • Teismann P, Schwaninger M, Weih F, Ferger B (2001) Nuclear factor-kappaB activation is not involved in a MPTP model of Parkinson’s disease. NeuroReport 12:1049–1053

    PubMed  CAS  Google Scholar 

  • Teunissen CE, Steinbusch HW, Angevaren M, Appels M, de Bruijn C, Prickaerts J, de Vente J (2001) Behavioural correlates of striatal glial fibrillary acidic protein in the 3-nitropropionic acid rat model: disturbed walking pattern and spatial orientation. Neuroscience 105:153–167

    PubMed  CAS  Google Scholar 

  • Theodore S, Cass WA, Nath A, Steiner J, Young K, Maragos WF (2006) Inhibition of tumor necrosis factor-alpha signaling prevents human immunodeficiency virus-1 protein Tat and methamphetamine interaction. Neurobiol Dis 23:663–668

    PubMed  CAS  Google Scholar 

  • Thomas DM, Kuhn DM (2005) MK-801 and dextromethorphan block microglial activation and protect against methamphetamine-induced neurotoxicity. Brain Res 1050:190–198

    PubMed  CAS  Google Scholar 

  • Thomas DM, Walker PD, Benjamins JA, Geddes TJ, Kuhn DM (2004) Methamphetamine neurotoxicity in dopamine nerve endings of the striatum is associated with microglial activation. J Pharmacol Exp Ther 311:1–7

    PubMed  CAS  Google Scholar 

  • Turrin NP, Rivest S (2006) Tumor necrosis factor alpha but not interleukin 1 beta mediates neuroprotection in response to acute nitric oxide excitotoxicity. J Neurosci 26:143–151

    PubMed  CAS  Google Scholar 

  • Tyor WR, Power C, Gendelman HE, Markham RB (1993) A model of human immunodeficiency virus encephalitis in scid mice. Proc Natl Acad Sci USA 90:8658–8662

    PubMed  CAS  Google Scholar 

  • Uno H, Matsuyama T, Akita H, Nishimura H, Sugita M (1997) Induction of tumor necrosis factor-alpha in the mouse hippocampus following transient forebrain ischemia. J Cereb Blood Flow Metab 17:491–499

    PubMed  CAS  Google Scholar 

  • Vanzani MC, Iacono RF, Caccuri RL, Troncoso AR, Berria MI (2006) Regional differences in astrocyte activation in HIV-associated dementia. Medicina (B Aires) 66:108–112

    Google Scholar 

  • Versijpt JJ, Dumont F, Van Laere KJ, Decoo D, Santens P, Audenaert K, Achten E, Slegers G, Dierckx RA, Korf J (2003) Assessment of neuroinflammation and microglial activation in Alzheimer’s disease with radiolabelled PK11195 and single photon emission computed tomography: a pilot study. Eur Neurol 50:39–47

    PubMed  CAS  Google Scholar 

  • Vila M, Jackson-Lewis V, Guegan C, Wu DC, Teismann P, Choi DK, Tieu K, Przedborski S (2001) The role of glial cells in Parkinson’s disease. Curr Opin Neurol 14:483–489

    PubMed  CAS  Google Scholar 

  • Vila N, Castillo J, Davalos A, Chamorro A (2000) Proinflammatory cytokines and early neurological worsening in ischemic stroke. Stroke 31:2325–2329

    PubMed  CAS  Google Scholar 

  • Villarroya H, Marie Y, Ouallet JC, Le Saux F, Tchelingerian JL, Baumann N (1997) Expression of TNF alpha in central neurons of Lewis rat spinal cord after EAE induction. J Neurosci Res 49:592–599

    PubMed  CAS  Google Scholar 

  • Wesselingh SL, Power C, Glass JD, Tyor WR, McArthur JC, Farber JM, Griffin JW, Griffin DE (1993) Intracerebral cytokine messenger RNA expression in acquired immunodeficiency syndrome dementia. Ann Neurol 33:576–582

    PubMed  CAS  Google Scholar 

  • Wesselingh SL, Takahashi K, Glass JD, McArthur JC, Griffin JW, Griffin DE (1997) Cellular localization of tumor necrosis factor mRNA in neurological tissue from HIV-infected patients by combined reverse transcriptase/polymerase chain reaction in situ hybridization and immunohistochemistry. J Neuroimmunol 74:1–8

    PubMed  CAS  Google Scholar 

  • Wierzba-Bobrowicz T, Gwiazda E, Kosno-Kruszewska E, Lewandowska E, Lechowicz W, Bertrand E, Szpak GM, Schmidt-Sidor B (2002) Morphological analysis of active microglia-rod and ramified microglia in human brains affected by some neurological diseases (SSPE, Alzheimer’s disease and Wilson’s disease). Folia Neuropathol 40:125–131

    PubMed  Google Scholar 

  • Wilson CM, Grace GM, Munoz DG, He BP, Strong MJ (2001) Cognitive impairment in sporadic ALS: a pathologic continuum underlying a multisystem disorder. Neurology 57:651–657

    PubMed  CAS  Google Scholar 

  • Zawadzka M, Kaminska B (2005) A novel mechanism of FK506-mediated neuroprotection: downregulation of cytokine expression in glial cells. Glia 49:36–51

    PubMed  Google Scholar 

  • Zhu W, Umegaki H, Shinkai T, Kurotani S, Suzuki Y, Endo H, Iguchi A (2003) Different glial reactions to hippocampal stab wounds in young adult and aged rats. J Gerontol A Biol Sci Med Sci 58:117–122

    PubMed  Google Scholar 

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  1. National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, CDC-NIOSH, 1095 Willowdale Road, Morgantown, WV, 26505, USA

    Krishnan Sriram & James P. O’Callaghan

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  1. Krishnan Sriram
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Correspondence to James P. O’Callaghan.

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Sriram, K., O’Callaghan, J.P. Divergent Roles for Tumor Necrosis Factor-α in the Brain. Jrnl Neuroimmune Pharm 2, 140–153 (2007). https://doi.org/10.1007/s11481-007-9070-6

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