Skip to main content

Advertisement

SpringerLink
Log in

Autoreactive antibodies against neurons and basal lamina found in serum following experimental brain contusion in rats

  • Experimental Research
  • Published:
Acta Neurochirurgica Aims and scope Submit manuscript

Summary

Background. Brain trauma is a risk factor for delayed CNS degeneration which may be attenuated by anti-inflammatory treatment. CNS injuries may cause anti-brain reactivity. This study was undertaken to analyze the pattern of delayed post-traumatic anti-brain immunity in experimental brain contusion.

Method. Adult Sprague-Dawley and Lewis rats were subjected to experimental brain contusions. For B-cell investigations, serum was obtained from contused, control and naïve rats, and used for immunohistochemistry on slices of rat brains to first detect autoreactive IgG and IgM antibodies in rat serum. Secondly, anti-rat IgG and IgM antibodies were used to search for auto-antibodies already bound to the brain tissue. Double staining with rat-serum and NeuN or anti-GFAP antibody was used to detect anti-neuronal and anti-astrocytic antibodies, respectively. For T-cell reactivity, cells from brains and cervical lymph nodes of rats were used in FACS analysis and elispot with MBP and MOG stimulation.

Findings. Anti-vascular basal lamina IgG antibodies were detected at three months in 6/8 rats, following experimental contusion. Anti-neuronal IgG antibodies were detected 2 weeks after experimental contusion and sham surgery, while naïve controls were negative. Individual rats showed a prolonged response, or an anti-astrocytic staining. Tissue bound anti-self IgG or IgM was not detected in the brain tissue. Anti-MBP or anti-MOG T-cell responses were not detectable.

Conclusions. Experimental brain trauma and to some degree even sham surgery lead to an individually variable pattern of specific anti-brain reactive B-cells, while a T-cell response did not seem to be a consequence of moderate experimental contusion. The mere presence of anti brain-antibodies may be epiphenomenal, but could also be pathogenic for delayed degeneration. It is reasonable to regard the presence of an actual anti-brain reactivity as a potential threat to brain tissue integrity.

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

Similar content being viewed by others

References

  • C Alling B Karlsson B Vallfors (1980) ArticleTitleIncrease in myelin basic protein in CSF after brain surgery. J Neurol 223 225–230 Occurrence Handle10.1007/BF00313336 Occurrence Handle1:STN:280:DyaL3M%2FgvVKktw%3D%3D Occurrence Handle6157784

    Article  CAS  PubMed  Google Scholar 

  • HM Bramlett WD Dietrich EJ Green R Busto (1997) ArticleTitleChronic histopathological consequences of fluid-percussion brain injury in rats: effects of post-traumatic hypothermia. Acta Neuropathol (Berl) 93 190–199 Occurrence Handle1:STN:280:DyaK2s7ptFGisg%3D%3D

    CAS  Google Scholar 

  • E Castigli R Fuleihan N Ramesh E Tsitsikov A Tsytsykova RS Geha (1995) ArticleTitleCD40 ligand/CD40 deficiency. Int Arch Allergy Immunol 107 37–39 Occurrence Handle1:CAS:528:DyaK2MXnsVWktLo%3D Occurrence Handle7542090 Occurrence Handle10.1159/000236923

    Article  CAS  PubMed  Google Scholar 

  • Clausen F, Hillered L (2005) Intracranial pressure changes during fluid percussion, controlled cortical impact and weight drop injury in rats. Acta Neurochir (Wien)

  • J Crimando K Cooper SA Hoffman (1997) ArticleTitleInhibition of sodium channel currents by antineuronal autoantibody from autoimmune mice. Ann N Y Acad Sci 823 303–307 Occurrence Handle1:CAS:528:DyaK2sXmt1Sqtbw%3D Occurrence Handle9292058

    CAS  PubMed  Google Scholar 

  • AH Cross JL Trotter J Lyons (2001) ArticleTitleB cells and antibodies in CNS demyelinating disease. J Neuroimmunol 112 1–14 Occurrence Handle10.1016/S0165-5728(00)00409-4 Occurrence Handle1:CAS:528:DC%2BD3cXosFeqsL0%3D Occurrence Handle11108928

    Article  CAS  PubMed  Google Scholar 

  • Dropcho EJ (2002) Remote neurologic manifestations of cancer. Neurol Clin 20: 85–122, vi

    Google Scholar 

  • DM Feeney MG Boyeson RT Linn HM Murray WG Dail (1981) ArticleTitleResponses to cortical injury: I. Methodology and local effects of contusions in the rat. Brain Res 211 67–77 Occurrence Handle10.1016/0006-8993(81)90067-6 Occurrence Handle1:CAS:528:DyaL3MXhslahtbc%3D Occurrence Handle7225844

    Article  CAS  PubMed  Google Scholar 

  • H Hammarberg O Lidman C Lundberg SY Eltayeb AW Gielen S Muhallab A Svenningsson H Linda PH van Der Meide S Cullheim T Olsson F Piehl (2000) ArticleTitleNeuroprotection by encephalomyelitis: rescue of mechanically injured neurons and neurotrophin production by CNS-infiltrating T and natural killer cells. J Neurosci 20 5283–5291 Occurrence Handle1:CAS:528:DC%2BD3cXlt1WitbY%3D Occurrence Handle10884312

    CAS  PubMed  Google Scholar 

  • B Hauss-Wegrzyniak JP Galons GL Wenk (2000) ArticleTitleQuantitative volumetric analyses of brain magnetic resonance imaging from rat with chronic neuroinflammation. Exp Neurol 165 347–354 Occurrence Handle10.1006/exnr.2000.7469 Occurrence Handle1:STN:280:DC%2BD3M%2FhtVOrsg%3D%3D Occurrence Handle10993694

    Article  CAS  PubMed  Google Scholar 

  • SA NA Hoffman DW Shucard RJ Harbeck (1988) ArticleTitleAutoantibodies, Immune complexes, and behavioral disorders: neuropsychiatric involvement in systemic lupus ertyhematosus. Arthritis Rheum 28 789–795

    Google Scholar 

  • S Holmin T Mathiesen (1999) ArticleTitleLong-term intracerebral inflammatory response after experimental focal brain injury in rat. Neuroreport 10 1889–1891 Occurrence Handle1:STN:280:DyaK1MvivFKgtw%3D%3D Occurrence Handle10501527

    CAS  PubMed  Google Scholar 

  • S Holmin T Mathiesen J Shetye P Biberfeld (1995) ArticleTitleIntracerebral inflammatory response to experimental brain contusion. Acta Neurochir (Wien) 132 110–119 Occurrence Handle10.1007/BF01404857 Occurrence Handle1:STN:280:DyaK2M3nsVCltg%3D%3D

    Article  CAS  Google Scholar 

  • S Holmin J Soderlund P Biberfeld T Mathiesen (1998) ArticleTitleIntracerebral inflammation after human brain contusion. Neurosurgery 42 291–298 Occurrence Handle1:STN:280:DyaK1c7ktFarsQ%3D%3D Occurrence Handle9482179

    CAS  PubMed  Google Scholar 

  • NR Hoyle PA Seeldrayers AH Moussa EA Paul DG Thomas (1984) ArticleTitlePre- and postoperative changes in serum myelin basic protein immunoreactivity in neurosurgical patients. J Neurosurg 61 49–52 Occurrence Handle1:STN:280:DyaL2c3hsFCitg%3D%3D Occurrence Handle6202857

    CAS  PubMed  Google Scholar 

  • ML Jenkinson MR Bliss AT Brain DL Scott (1989) ArticleTitleRheumatoid arthritis and senile dementia of the Alzheimer’s type. Br J Rheumatol 28 86–88 Occurrence Handle1:STN:280:DyaL1M7jsFChuw%3D%3D Occurrence Handle2917245

    CAS  PubMed  Google Scholar 

  • YI Kim E Neher (1988) ArticleTitleIgG from patients with Lambert-Eaton syndrome blocks voltage-dependent calcium channels. Science 239 405–408 Occurrence Handle1:STN:280:DyaL1c%2FpvFGhtw%3D%3D Occurrence Handle2447652

    CAS  PubMed  Google Scholar 

  • H Lopez-Escribano E Minambres M Labrador MJ Bartolome M Lopez-Hoyos (2002) ArticleTitleInduction of cell death by sera from patients with acute brain injury as a mechanism of production of autoantibodies. Arthritis Rheum 46 3290–3300 Occurrence Handle12483734 Occurrence Handle10.1002/art.10684

    Article  PubMed  Google Scholar 

  • G Moalem R Leibowitz-Amit E Yoles F Mor IR Cohen M Schwartz (1999) ArticleTitleAutoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat Med 5 49–55 Occurrence Handle1:CAS:528:DyaK1MXmtFKktw%3D%3D Occurrence Handle9883839

    CAS  PubMed  Google Scholar 

  • G Moalem A Monsonego Y Shani IR Cohen M Schwartz (1999) ArticleTitleDifferential T cell response in central and peripheral nerve injury: connection with immune privilege. Faseb J 13 1207–1217 Occurrence Handle1:CAS:528:DyaK1MXktlOrur4%3D Occurrence Handle10385611

    CAS  PubMed  Google Scholar 

  • SG Morozov LM Asanova BB Gnedenko LF Panchenko TN Lavrova (1996) ArticleTitle[Autoantibodies against nerve tissue proteins long after cranio-cerebral injury]. Vopr Med Khim 42 147–152 Occurrence Handle1:CAS:528:DyaK28Xmslehtr0%3D Occurrence Handle9148602

    CAS  PubMed  Google Scholar 

  • S Muhallab O Lidman R Weissert T Olsson A Svenningsson (2001) ArticleTitleIntra-CNS activation by antigen-specific T lymphocytes in experimental autoimmune encephalomyelitis. J Neuroimmunol 113 202–211 Occurrence Handle10.1016/S0165-5728(00)00438-0 Occurrence Handle1:CAS:528:DC%2BD3MXnsVWitQ%3D%3D Occurrence Handle11164903

    Article  CAS  PubMed  Google Scholar 

  • T Olsson P Diener A Ljungdahl B Hojeberg PH van der Meide K Kristensson (1992) ArticleTitleFacial nerve transection causes expansion of myelin autoreactive T cells in regional lymph nodes and T cell homing to the facial nucleus. Autoimmunity 13 117–126 Occurrence Handle1:STN:280:DyaK3s7gsVertA%3D%3D Occurrence Handle1281678

    CAS  PubMed  Google Scholar 

  • M Popovic M Caballero-Bleda L Puelles N Popovic (1998) ArticleTitleImportance of immunological and inflammatory processes in the pathogenesis and therapy of Alzheimer’s disease. Int J Neurosci 95 203–236 Occurrence Handle1:STN:280:DyaK1cvltVKitw%3D%3D Occurrence Handle9777440

    CAS  PubMed  Google Scholar 

  • PG Popovich Z Guan P Wei I Huitinga N van Rooijen BT Stokes (1999) ArticleTitleDepletion of hematogenous macrophages promotes partial hindlimb recovery and neuroanatomical repair after experimental spinal cord injury. Exp Neurol 158 351–365 Occurrence Handle10.1006/exnr.1999.7118 Occurrence Handle1:CAS:528:DyaK1MXksFams7o%3D Occurrence Handle10415142

    Article  CAS  PubMed  Google Scholar 

  • PG Popovich BT Stokes CC Whitacre (1996) ArticleTitleConcept of autoimmunity following spinal cord injury: possible roles for T lymphocytes in the traumatized central nervous system. J Neurosci Res 45 349–363 Occurrence Handle10.1002/(SICI)1097-4547(19960815)45:4<349::AID-JNR4>3.0.CO;2-9 Occurrence Handle1:CAS:528:DyaK28XlsVOks70%3D Occurrence Handle8872895

    Article  CAS  PubMed  Google Scholar 

  • PG Popovich P Wei BT Stokes (1997) ArticleTitleCellular inflammatory response after spinal cord injury in Sprague-Dawley and Lewis rats. J Comp Neurol 377 443–464 Occurrence Handle10.1002/(SICI)1096-9861(19970120)377:3<443::AID-CNE10>3.0.CO;2-S Occurrence Handle1:STN:280:DyaK2s7ktlKntA%3D%3D Occurrence Handle8989657

    Article  CAS  PubMed  Google Scholar 

  • J Rogers LC Kirby SR Hempelman DL Berry PL McGeer AW Kaszniak J Zalinski M Cofield L Mansukhani P Willson et al. (1993) ArticleTitleClinical trial of indomethacin in Alzheimer’s disease. Neurology 43 1609–1611 Occurrence Handle1:STN:280:DyaK3szlsVGrtw%3D%3D Occurrence Handle8351023

    CAS  PubMed  Google Scholar 

  • JV Rutter A Jehanli R Harrison GG Lunt (1987) ArticleTitleImmunological factors in neuronal degeneration with particular reference to motor neurone disease. Gerontology 33 187–192 Occurrence Handle1:STN:280:DyaL1c%2FgsFyisQ%3D%3D Occurrence Handle3653701 Occurrence Handle10.1159/000212874

    Article  CAS  PubMed  Google Scholar 

  • PA Seeldrayers NR Hoyle DG Thomas (1984) ArticleTitlePre- and post-operative changes in serum immunoglobulin level in neurosurgical patients. Acta Neurochir (Wien) 70 269–274 Occurrence Handle10.1007/BF01406655 Occurrence Handle1:STN:280:DyaL2c7nsFCjsQ%3D%3D

    Article  CAS  Google Scholar 

  • T Shiozaki H Akai M Taneda T Hayakata M Aoki J Oda H Tanaka A Hiraide T Shimazu H Sugimoto (2001) ArticleTitleDelayed hemispheric neuronal loss in severely head-injured patients. J Neurotrauma 18 665–674 Occurrence Handle10.1089/089771501750357618 Occurrence Handle1:STN:280:DC%2BD3MvltFCrtg%3D%3D Occurrence Handle11497093

    Article  CAS  PubMed  Google Scholar 

  • S Sinha J Newsom-Davis K Mills N Byrne B Lang A Vincent (1991) ArticleTitleAutoimmune aetiology for acquired neuromyotonia (Isaacs’ syndrome). Lancet 338 75–77 Occurrence Handle10.1016/0140-6736(91)90073-X Occurrence Handle1:STN:280:DyaK3M3oslChtQ%3D%3D Occurrence Handle1676468

    Article  CAS  PubMed  Google Scholar 

  • M Sjogren A Wallin (2001) ArticleTitlePathophysiological aspects of frontotemporal dementia – emphasis on cytoskeleton proteins and autoimmunity. Mech Ageing Dev 122 1923–1935 Occurrence Handle1:CAS:528:DC%2BD3MXnt1Sit7s%3D Occurrence Handle11589911

    CAS  PubMed  Google Scholar 

  • I Stankova L Prokesova S Trojan (1999) ArticleTitleIs the identification of antibodies against the nervous tissue an indicator of brain injury? Physiol Res 48 383–387 Occurrence Handle1:STN:280:DC%2BD3c%2FovVGltA%3D%3D Occurrence Handle10625228

    CAS  PubMed  Google Scholar 

  • TD Stein JP Fedynyshyn RE Kalil (2002) ArticleTitleCirculating autoantibodies recognize and bind dying neurons following injury to the brain. J Neuropathol Exp Neurol 61 1100–1108 Occurrence Handle12484573

    PubMed  Google Scholar 

  • DG Thomas NR Hoyle P Seeldrayers (1984) ArticleTitleMyelin basic protein immunoreactivity in serum of neurosurgical patients. J Neurol Neurosurg Psychiatry 47 173–175 Occurrence Handle1:STN:280:DyaL2c7mtl2nsA%3D%3D Occurrence Handle6200573

    CAS  PubMed  Google Scholar 

  • DM Waterhouse RB Natale RL Cody (1991) ArticleTitleBreast cancer and paraneoplastic cerebellar degeneration. Cancer 68 1835–1841 Occurrence Handle1:STN:280:DyaK38%2FgsFaktQ%3D%3D Occurrence Handle1913530

    CAS  PubMed  Google Scholar 

  • R Weissert A Svenningsson A Lobell KL de Graaf R Andersson T Olsson (1998) ArticleTitleMolecular and genetic requirements for preferential recruitment of TCRBV8S2+ T cells in Lewis rat experimental autoimmune encephalomyelitis. J Immunol 160 681–690 Occurrence Handle1:CAS:528:DyaK1cXls1Cjsw%3D%3D Occurrence Handle9551903

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Neuroscience, Section of Neurosurgery, Karolinska Institute, Stockholm, Sweden

    S. Rudehill, A. Wennersten, C. von Gertten, F. Al Nimer, A. C. Sandberg-Nordqvist, S. Holmin & T. Mathiesen

  2. Neuroimmunology Unit, Center of Molecular Medicine, Department of Medicine, Karolinska Institute, Stockholm, Sweden

    S. Muhallab

Authors
  1. S. Rudehill
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Muhallab
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Wennersten
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. von Gertten
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. F. Al Nimer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. C. Sandberg-Nordqvist
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S. Holmin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. T. Mathiesen
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rudehill, S., Muhallab, S., Wennersten, A. et al. Autoreactive antibodies against neurons and basal lamina found in serum following experimental brain contusion in rats. Acta Neurochir (Wien) 148, 199–205 (2006). https://doi.org/10.1007/s00701-005-0673-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00701-005-0673-5

Search

Navigation