Skip to main content

Advertisement

SpringerLink
Log in

Debate: “Is Increasing Neuroinflammation Beneficial for Neural Repair?”

  • Invited Review
  • Published:
Journal of Neuroimmune Pharmacology Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  • Aharoni R, Arnon R, Eilam R (2005) Neurogenesis and neuroprotection induced by peripheral immunomodulatory treatment of experimental autoimmune encephalomyelitis. J Neurosci 25:8217–8228

    Article  PubMed  CAS  Google Scholar 

  • Anderson ER, Boyle J, Zink WE, Persidsky Y, Gendelman HE, Xiong H (2003) Hippocampal synaptic dysfunction in a murine model of human immunodeficiency virus type 1 encephalitis. Neuroscience 118:359–369

    Article  PubMed  CAS  Google Scholar 

  • Arnon R, Teitelbaum D, Sela M (1989) Suppression of experimental allergic encephalomyelitis by COP1—relevance to multiple sclerosis. Isr J Med Sci 25:686–689

    PubMed  CAS  Google Scholar 

  • Bakalash S, Shlomo GB, Aloni E, Shaked I, Wheeler L, Ofri R, Schwartz M (2005) T-cell-based vaccination for morphological and functional neuroprotection in a rat model of chronically elevated intraocular pressure. J Mol Med 83:904–916

    Article  PubMed  Google Scholar 

  • Bao F, Chen Y, Dekaban GA, Weaver LC (2004) Early anti-inflammatory treatment reduces lipid peroxidation and protein nitration after spinal cord injury in rats. J Neurochem 88:1335–1344

    Article  PubMed  CAS  Google Scholar 

  • Bao F, Dekaban GA, Weaver LC (2005) Anti-CD11d antibody treatment reduces free radical formation and cell death in the injured spinal cord of rats. J Neurochem 94:1361–1373

    Article  PubMed  CAS  Google Scholar 

  • Benner EJ, Mosley RL, Destache CJ, Lewis TB, Jackson-Lewis V, Gorantla S, Nemachek C, Green SR, Przedborski S, Gendelman HE (2004) Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson’s disease. Proc Natl Acad Sci USA 101:9435–9440

    Article  PubMed  CAS  Google Scholar 

  • Blight AR (1994) Effects of silica on the outcome from experimental spinal cord injury: implication of macrophages in secondary tissue damage. Neuroscience 60:263–273

    Article  PubMed  CAS  Google Scholar 

  • Boche D, Nicoll JA, Weller RO (2005) Immunotherapy for Alzheimer’s disease and other dementias. Curr Opin Neurol 18:720–725

    Article  PubMed  CAS  Google Scholar 

  • Boska MD, Lewis TB, Destache CJ, Benner EJ, Nelson JA, Uberti M, Mosley RL, Gendelman HE (2005) Quantitative 1H magnetic resonance spectroscopic imaging determines therapeutic immunization efficacy in an animal model of Parkinson’s disease. J Neurosci 25:1691–1700

    Article  PubMed  CAS  Google Scholar 

  • Brown A, Ricci MJ, Weaver LC (2004) NGF message and protein distribution in the injured rat spinal cord. Exp Neurol 188:115–127

    Article  PubMed  CAS  Google Scholar 

  • Chen V (2005) Novel method of treating Alzheimer’s disease. Lancet Neurol 4:599

    Article  PubMed  Google Scholar 

  • Cohen IR, Schwartz M (1999) Autoimmune maintenance and neuroprotection of the central nervous system. J Neuroimmunol 100:111–114

    Article  PubMed  CAS  Google Scholar 

  • Dou H, Birusingh K, Faraci J, Gorantla S, Poluektova LY, Maggirwar SB, Dewhurst S, Gelbard HA, Gendelman HE (2003) Neuroprotective activities of sodium valproate in a murine model of human immunodeficiency virus-1 encephalitis. J Neurosci 23:9162–9170

    PubMed  CAS  Google Scholar 

  • Dou H, Kingsley JD, Mosley RL, Gelbard HA, Gendelman HE (2004) Neuroprotective strategies for HIV-1 associated dementia. Neurotox Res 6:503–521

    PubMed  Google Scholar 

  • Edling AE, Tuohy VK (2005) Stem cell reconstitution of autoimmune T cell repertoires. J Neuroimmunol 169:126–136

    Article  PubMed  CAS  Google Scholar 

  • Fischer D, Petkova V, Thanos S, Benowitz LI (2004) Switching mature retinal ganglion cells to a robust growth state in vivo: gene expression and synergy with RhoA inactivation. J Neurosci 24:8726–8740

    Article  PubMed  CAS  Google Scholar 

  • Fisher J, Levkovitch-Verbin H, Schori H, Yoles E, Butovsky O, Kaye JF, Ben-Nun A, Schwartz M (2001) Vaccination for neuroprotection in the mouse optic nerve: implications for optic neuropathies. J Neurosci 21:136–142

    PubMed  CAS  Google Scholar 

  • Fleming JC NM, Ramsay DA, Marcillo AE, Saenz AD, Dietrich WD, Weaver LC (2005) The acute cellular inflammatory response after human spinal cord injury. J Neurotrauma 22:1170

    Google Scholar 

  • Frenkel D, Maron R, Burt DS, Weiner HL (2005) Nasal vaccination with a proteosome-based adjuvant and glatiramer acetate clears beta-amyloid in a mouse model of Alzheimer disease. J Clin Invest 115:2423–2433

    Article  PubMed  CAS  Google Scholar 

  • Gendelman HE, Meltzer MS (1989) Mononuclear phagocytes and the human immunodeficiency virus. Curr Opin Immunol 2:414–419

    Article  PubMed  Google Scholar 

  • Gendelman HE, Narayan O, Molineaux S, Clements JE, Ghotbi Z (1985) Slow, persistent replication of lentiviruses: role of tissue macrophages and macrophage precursors in bone marrow. Proc Natl Acad Sci USA 82:7086–7090

    Article  PubMed  CAS  Google Scholar 

  • Gendelman HE, Phelps W, Feigenbaum L, Ostrove JM, Adachi A, Howley PM, Khoury G, Ginsberg HS, Martin MA (1986) Trans-activation of the human immunodeficiency virus long terminal repeat sequence by DNA viruses. Proc Natl Acad Sci USA 83:9759–9763

    Article  PubMed  CAS  Google Scholar 

  • Gendelman HE, Leonard JM, Dutko F, Koenig S, Khillan J, Meltzer MS (1988) Immunopathogenesis of human immunodeficiency virus infection in the central nervous system. Ann Neurol 23 Suppl:S78–S81

    Article  PubMed  Google Scholar 

  • Gendelman HE, Orenstein JM, Baca LM, Weiser B, Burger H, Kalter DC, Meltzer MS (1989) The macrophage in the persistence and pathogenesis of HIV infection. Aids 3:475–495

    Article  PubMed  CAS  Google Scholar 

  • Genis P, Jett M, Bernton EW, Boyle T, Gelbard HA, Dzenko K, Keane RW, Resnick L, Mizrachi Y, Volsky DJ, et al. (1992) Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophage–astroglia interactions: implications for the neuropathogenesis of HIV disease. J Exp Med 176:1703–1718

    Article  PubMed  CAS  Google Scholar 

  • Giulian D, Robertson C (1990) Inhibition of mononuclear phagocytes reduces ischemic injury in the spinal cord. Ann Neurol 27:33–42

    Article  PubMed  CAS  Google Scholar 

  • Giulian D, Vaca K, Corpuz M (1993) Brain glia release factors with opposing actions upon neuronal survival. J Neurosci 13:29–37

    PubMed  CAS  Google Scholar 

  • Gris D, Marsh DR, Oatway MA, Chen Y, Hamilton EF, Dekaban GA, Weaver LC (2004) Transient blockade of the CD11d/CD18 integrin reduces secondary damage after spinal cord injury, improving sensory, autonomic, and motor function. J Neurosci 24:4043–4051

    Article  PubMed  CAS  Google Scholar 

  • Jiang ZG, Piggee C, Heyes MP, Murphy C, Quearry B, Bauer M, Zheng J, Gendelman HE, Markey SP (2001) Glutamate is a mediator of neurotoxicity in secretions of activated HIV-1-infected macrophages. J Neuroimmunol 117:97–107

    Article  PubMed  CAS  Google Scholar 

  • Kadiu I, Glanzer JG, Kipnis J, Gendelman HE, Thomas MP (2005) Mononuclear phagocytes in the pathogenesis of neurodegenerative diseases. Neurotox Res 8:25–50

    Article  PubMed  CAS  Google Scholar 

  • Kempermann G, Wiskott L, Gage FH (2004) Functional significance of adult neurogenesis. Curr Opin Neurobiol 14:186–191

    Article  PubMed  CAS  Google Scholar 

  • Kempermann G, Chesler EJ, Lu L, Williams RW, Gage FH (2006) Natural variation and genetic covariance in adult hippocampal neurogenesis. Proc Natl Acad Sci USA 103:780–785

    Article  PubMed  CAS  Google Scholar 

  • Kipnis J, Schwartz M (2002) Dual action of glatiramer acetate (Cop-1) in the treatment of CNS autoimmune and neurodegenerative disorders. Trends Mol Med 8:319–323

    Article  PubMed  CAS  Google Scholar 

  • Kipnis J, Yoles E, Porat Z, Cohen A, Mor F, Sela M, Cohen IR, Schwartz M (2000) T cell immunity to copolymer 1 confers neuroprotection on the damaged optic nerve: possible therapy for optic neuropathies. Proc Natl Acad Sci USA 97:7446–7451

    Article  PubMed  CAS  Google Scholar 

  • Kipnis J, Yoles E, Schori H, Hauben E, Shaked I, Schwartz M (2001) Neuronal survival after CNS insult is determined by a genetically encoded autoimmune response. J Neurosci 21:4564–4571

    PubMed  CAS  Google Scholar 

  • Kipnis J, Nevo U, Panikashvili D, Alexandrovich A, Yoles E, Akselrod S, Shohami E, Schwartz M (2003) Therapeutic vaccination for closed head injury. J Neurotrauma 20:559–569

    Article  PubMed  Google Scholar 

  • Koenig S, Gendelman HE, Orenstein JM, Dal Canto MC, Pezeshkpour GH, Yungbluth M, Janotta F, Aksamit A, Martin MA, Fauci AS (1986) Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science 233:1089–1093

    Article  PubMed  CAS  Google Scholar 

  • Leibovich SJ, Ross R (1975) The role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum. Am J Pathol 78:71–100

    PubMed  CAS  Google Scholar 

  • Leskovar A, Moriarty LJ, Turek JJ, Schoenlein IA, Borgens RB (2000) The macrophage in acute neural injury: changes in cell numbers over time and levels of cytokine production in mammalian central and peripheral nervous systems. J Exp Biol 203:1783–1795

    PubMed  CAS  Google Scholar 

  • Mabon PJ, Weaver LC, Dekaban GA (2000) Inhibition of monocyte/macrophage migration to a spinal cord injury site by an antibody to the integrin alphaD: a potential new anti-inflammatory treatment. Exp Neurol 166:52–64

    Article  PubMed  CAS  Google Scholar 

  • Martin P, D’Souza D, Martin J, Grose R, Cooper L, Maki R, McKercher SR (2003) Wound healing in the PU.1 null mouse-tissue repair is not dependent on inflammatory cells. Curr Biol 13:1122–1128

    Article  PubMed  CAS  Google Scholar 

  • Meltzer MS, Skillman DR, Gomatos PJ, Kalter DC, Gendelman HE (1990) Role of mononuclear phagocytes in the pathogenesis of human immunodeficiency virus infection. Annu Rev Immunol 8:169–194

    Article  PubMed  CAS  Google Scholar 

  • Moalem G, Monsonego A, Shani Y, Cohen IR, Schwartz M (1999a) Differential T cell response in central and peripheral nerve injury: connection with immune privilege. FASEB J 13:1207–1217

    PubMed  CAS  Google Scholar 

  • Moalem G, Leibowitz-Amit R, Yoles E, Mor F, Cohen IR, Schwartz M (1999b) Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat Med 5:49–55

    Article  PubMed  CAS  Google Scholar 

  • Oatway MA, Chen Y, Bruce JC, Dekaban GA, Weaver LC (2005) Anti-CD11d integrin antibody treatment restores normal serotonergic projections to the dorsal, intermediate, and ventral horns of the injured spinal cord. J Neurosci 25:637–647

    Article  PubMed  CAS  Google Scholar 

  • Persidsky Y, Gendelman HE (2003) Mononuclear phagocyte immunity and the neuropathogenesis of HIV-1 infection. J Leukoc Biol 74:691–701

    Article  PubMed  CAS  Google Scholar 

  • Poluektova L, Gorantla S, Faraci J, Birusingh K, Dou H, Gendelman HE (2004) Neuroregulatory events follow adaptive immune-mediated elimination of HIV-1-infected macrophages: studies in a murine model of viral encephalitis. J Immunol 172:7610–7617

    PubMed  CAS  Google Scholar 

  • Popovich PG, Guan Z, Wei P, Huitinga I, van Rooijen N, Stokes BT (1999) Depletion of hematogenous macrophages promotes partial hindlimb recovery and neuroanatomical repair after experimental spinal cord injury. Exp Neurol 158:351–365

    Article  PubMed  CAS  Google Scholar 

  • Popovich PG, Guan Z, McGaughy V, Fisher L, Hickey WF, Basso DM (2002) The neuropathological and behavioral consequences of intraspinal microglial/macrophage activation. J Neuropathol Exp Neurol 61:623–633

    PubMed  CAS  Google Scholar 

  • Rapalino O, Lazarov-Spiegler O, Agranov E, Velan GJ, Yoles E, Fraidakis M, Solomon A, Gepstein R, Katz A, Belkin M, Hadani M, Schwartz M (1998) Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nat Med 4:814–821

    Article  PubMed  CAS  Google Scholar 

  • Ryan LA, Peng H, Erichsen DA, Huang Y, Persidsky Y, Zhou Y, Gendelman HE, Zheng J (2004) TNF-related apoptosis-inducing ligand mediates human neuronal apoptosis: links to HIV-1-associated dementia. J Neuroimmunol 148:127–139

    Article  PubMed  CAS  Google Scholar 

  • Saville LR, Pospisil CH, Mawhinney LA, Bao F, Simedrea FC, Peters AA, O’Connell PJ, Weaver LC, Dekaban GA (2004) A monoclonal antibody to CD11d reduces the inflammatory infiltrate into the injured spinal cord: a potential neuroprotective treatment. J Neuroimmunol 156:42–57

    Article  PubMed  CAS  Google Scholar 

  • Schifitto G, Peterson DR, Zhong J, Ni H, Cruttenden K, Gaugh M, Gendelman HE, Boska M, Gelbard H (2006) Valproic acid adjunctive therapy for HIV-associated cognitive impairment. A first report. Neurology 66:919–921

    Article  PubMed  CAS  Google Scholar 

  • Schori H, Kipnis J, Yoles E, WoldeMussie E, Ruiz G, Wheeler LA, Schwartz M (2001) Vaccination for protection of retinal ganglion cells against death from glutamate cytotoxicity and ocular hypertension: implications for glaucoma. Proc Natl Acad Sci USA 98:3398–3403

    Article  PubMed  CAS  Google Scholar 

  • Schwartz M (2000a) Beneficial autoimmune T cells and posttraumatic neuroprotection. Ann N Y Acad Sci 917:341–347

    Article  PubMed  CAS  Google Scholar 

  • Schwartz M (2000b) Autoimmune involvement in CNS trauma is beneficial if well controlled. Prog Brain Res 128:259–263

    Article  PubMed  CAS  Google Scholar 

  • Schwartz M (2003) Macrophages and microglia in central nervous system injury: are they helpful or harmful? J Cereb Blood Flow Metab 23:385–394

    Article  PubMed  Google Scholar 

  • Schwartz M, Kipnis J (2005) Therapeutic T cell-based vaccination for neurodegenerative disorders: the role of CD4+CD25+ regulatory T cells. Ann N Y Acad Sci 1051:701–708

    Article  PubMed  CAS  Google Scholar 

  • Sela M (1999) Specific vaccines against autoimmune diseases. CR Acad Sci III 322:933–938

    CAS  Google Scholar 

  • Sela M (2000) Structural components responsible for peptide antigenicity. Appl Biochem Biotechnol 83:63–70; discussion 145–153

    Article  PubMed  CAS  Google Scholar 

  • Shaked I, Tchoresh D, Gersner R, Meiri G, Mordechai S, Xiao X, Hart RP, Schwartz M (2005) Protective autoimmunity: interferon-gamma enables microglia to remove glutamate without evoking inflammatory mediators. J Neurochem 92:997–1009

    Article  PubMed  CAS  Google Scholar 

  • Shibata A, Zelivyanskaya M, Limoges J, Carlson KA, Gorantla S, Branecki C, Bishu S, Xiong H, Gendelman HE (2003) Peripheral nerve induces macrophage neurotrophic activities: regulation of neuronal process outgrowth, intracellular signaling and synaptic function. J Neuroimmunol 142:112–129

    Article  PubMed  CAS  Google Scholar 

  • Shors TJ (2004) Memory traces of trace memories: neurogenesis, synaptogenesis and awareness. Trends Neurosci 27:250–256

    Article  PubMed  CAS  Google Scholar 

  • Teng HK, Teng KK, Lee R, Wright S, Tevar S, Almeida RD, Kermani P, Torkin R, Chen ZY, Lee FS, Kraemer RT, Nykjaer A, Hempstead BL (2005) ProBDNF induces neuronal apoptosis via activation of a receptor complex of p75NTR and sortilin. J Neurosci 25:5455–5463

    Article  PubMed  CAS  Google Scholar 

  • Weaver LC, Gris D, Saville LR, Oatway MA, Chen Y, Marsh DR, Hamilton EF, Dekaban GA (2005) Methylprednisolone causes minimal improvement after spinal cord injury in rats, contrasting with benefits of an anti-integrin treatment. J Neurotrauma 22:1375–1387

    Article  PubMed  Google Scholar 

  • Wirth III E (2005) Clinical Trials in SCI: How can we link imaging to functional outcome. In: 11th International Symposium on Neural Regeneration. Pacific Grove, CA

  • Yoles E, Hauben E, Palgi O, Agranov E, Gothilf A, Cohen A, Kuchroo V, Cohen IR, Weiner H, Schwartz M (2001) Protective autoimmunity is a physiological response to CNS trauma. J Neurosci 21:3740–3748

    PubMed  CAS  Google Scholar 

  • Ziv Y, Ron N, Butovsky O, Landa G, Sudai E, Greenberg N, Cohen H, Kipnis J, Schwartz M (2006) Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nat Neurosci 9:268–275

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The participants and organizers of the debate are thankful to the following sponsors for making this meeting possible: the US Department of Veterans Affairs (Biomedical Laboratory Research and Development Service and Office of Research and Development), Paralyzed Veterans of America (Education Foundation), National Institutes of Health (National Institute of Neurological Disorders and Stroke and Office of Rare Diseases), Christopher Reeve Paralysis Foundation, United Spinal Association, and the Shapiro Spinal Cord Research Foundation.

Author information

Authors and Affiliations

  1. Department of Neurosurgery (MSB 4313), University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH, 45267-0515, USA

    Keith A. Crutcher

  2. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center, Omaha, NE, 68198-5880, USA

    Howard E. Gendelman & Jonathan Kipnis

  3. Biochemistry and Molecular Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0652, USA

    J. Regino Perez-Polo

  4. Department of Pathology and Clinical Neurosciences, Biomedical Sciences Building, University of Southampton, Southampton, SO16 7PX, UK

    V. H. Perry

  5. Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, 2078 Graves Hall, 333 West 10th Ave., Columbus, OH, 43210, USA

    Phillip G. Popovich

  6. Robarts Research Institute, Spinal Cord Injury Laboratory, BioTherapeutics Research Group, P.O. Box 5015, 100 Perth Drive, London, ON, N6A 5K8, Canada

    Lynne C. Weaver

Authors
  1. Keith A. Crutcher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Howard E. Gendelman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jonathan Kipnis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Regino Perez-Polo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. V. H. Perry
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Phillip G. Popovich
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lynne C. Weaver
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Keith A. Crutcher.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Crutcher, K.A., Gendelman, H.E., Kipnis, J. et al. Debate: “Is Increasing Neuroinflammation Beneficial for Neural Repair?”. Jrnl Neuroimmune Pharm 1, 195–211 (2006). https://doi.org/10.1007/s11481-006-9021-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11481-006-9021-7

Key words

Search

Navigation