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Chronic spinal nerve ligation induces microvascular permeability disturbances, astrocytic reaction, and structural changes in the rat spinal cord

  • Conference paper
Brain Edema XIII

Part of the book series: Acta Neurochirurgica Supplementum ((NEUROCHIRURGICA,volume 96))

Summary

The possibility that a chronic nerve ligation impairs the spinal cord cellular microenvironment was examined using leakage of endogenous albumin, reaction of astrocytes, and structural changes in a rat model. Rats subjected to 8 weeks of unilateral L4/L5 nerve ligation (a model of neuropathic pain) showed leakage of albumin, up-regulation of glial fibrillary acidic protein (GFAP) immunoreaction, and abnormal cell reaction. Distortion and loss of nerve cells as well as general sponginess of the gray matter was clearly evident. Cell changes were present in both dorsal and ventral horns and were most marked on the ipsilateral side compared to the contralateral cord. Nerve cell and glial cell changes are normally present in the regions showing intense albumin immunoreactivity, indicating disruption of the blood-spinal cord barrier (BSCB). Our observations indicate that a chronic nerve lesion has the capacity to induce selective breakdown of the BSCB that could be responsible for activation of astrocytes and abnormal cell reaction. These findings enhance our understanding of the pathophysiology of neuropathic pain and/or other spinal cord disorders.

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References

  1. Aquino DA, Chiu FC, Brosnan CF, Norton WT (1988) Glial fibrillary acidic protein increases in the spinal cord of Lewis rats with acute experimental autoimmuno encephalomyelitis. J Neurochem 51: 1085–1096

    PubMed  CAS  Google Scholar 

  2. Beck DW, Roberts RL, Olson JJ (1986) Glial cells influence membrane-associated enzyme activity at the blood-brain barrier. Brain Res 381: 131–137

    Article  PubMed  CAS  Google Scholar 

  3. Bernstein JJ, Goldberg WJ (1987) Injury-related spinal cord astrocytes are immunoglobulin-positive (IgM and/or IgG) at different time periods in the regenerative process. Brain Res 426: 112–118

    Article  PubMed  CAS  Google Scholar 

  4. Bignami A, Dahl D, Rueger DC (1980) Glial fibrillary acidic protein (GFA) in normal neural cells and in pathological conditions. Adv Cell Neurobiol 1: 285–319

    CAS  Google Scholar 

  5. Bologa L, Cole R, Chiappelli F, Saneto RP, De Villis J (1988) Expression of glial fibrillary acidic protein by differentiated astrocytes is regulated by serum antagonistic factors. Brain Res 457: 295–302

    Article  PubMed  CAS  Google Scholar 

  6. Cervos-Navarro J, Sharma HS, Westman J, Bongcam-Rudloff E (1998) Glial reactions in the central nervous system following heat stress. Prog Brain Res 115: 241–274

    Article  PubMed  CAS  Google Scholar 

  7. Chung JM, Choi Y, Yoon YW, Na HS (1995) Effects of age on behavioral signs of neuropathic pain in an experimental rat model. Neurosci Lett 183: 54–57

    Article  PubMed  CAS  Google Scholar 

  8. Chung JM, Kim HK, Chung K (2004) Segmental spinal nerve ligation model of neuropathic pain. Methods Mol Med 99: 35–45

    PubMed  Google Scholar 

  9. Dubner R, Ruda MA (1992) Activity-dependent neuronal plasticity following tissue injury and inflammation. Trends Neurosci 15: 96–103

    Article  PubMed  CAS  Google Scholar 

  10. Goldman JE, Abramson B (1990) Cyclic AMP-induced shape changes of astrocytes are accompanied by rapid depolymerization of actin. Brain Res 528: 189–196

    Article  PubMed  CAS  Google Scholar 

  11. Gordh T, Sharma HS, Alm P, Westman J (1998) Spinal nerve lesion induces upregulation of neuronal nitric oxide synthase in the spinal cord. An immunohistochemical investigation in the rat. Amino Acids 14: 105–112

    Article  PubMed  CAS  Google Scholar 

  12. Gordh T, Sharma HS, Azizi M, Alm P, Westman J (2000) Spinal nerve lesion induces upregulation of constitutive isoform of heme oxygenase in the spinal cord. An immunohistochemical investigation in the rat. Amino Acids 19: 373–381

    Article  PubMed  CAS  Google Scholar 

  13. Gordh T, Chu H, Sharma HS (2005) Spinal nerve lesion alters blood-spinal cord barrier function and activates astrocytes. An immunohistochemical study using albumin and glial fibrillary acidic protein in the rat. Pain (in press)

    Google Scholar 

  14. Goshgarian HG, Yu XJ, Rafols JA (1989) Neuronal and glial changes in the rat phrenic nucleus occurring within hours after spinal cord injury. J Comp Neurol 284: 519–533

    Article  PubMed  CAS  Google Scholar 

  15. Kim SH, Chung JM (1992) An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 50: 355–363

    Article  PubMed  CAS  Google Scholar 

  16. LaBuda CJ, Little PJ (2005) Pharmacological evaluation of the selective spinal nerve ligation model of neuropathic pain in the rat. J Neurosci Methods 144: 175–181

    PubMed  CAS  Google Scholar 

  17. Murphy S, Pearce B (1987) Functional receptors for neurotransmitters on astroglial cells. Neuroscience 22: 381–394

    Article  PubMed  CAS  Google Scholar 

  18. Polgar E, Hughes DI, Arham AZ, Todd AJ (2005) Loss of neurons from laminas I-III of the spinal dorsal horn is not required for development of tactile allodynia in the spared nerve injury model of neuropathic pain. J Neurosci 25: 6658–6666

    Article  PubMed  CAS  Google Scholar 

  19. Schmidt-Kastner R, Freund TF (1991) Selective vulnerability of the hippocampus in brain ischemia. Neuroscience 40: 599–636

    Article  PubMed  CAS  Google Scholar 

  20. Sharma HS (1998) Neurobiology of the nitric oxide in the nervous system. Basic and clinical perspectives. Amino Acids 14: 83–85

    Article  PubMed  CAS  Google Scholar 

  21. Sharma HS (2004) Blood-brain and spinal cord barriers in stress. In: Sharma HS, Westman J (eds) Blood-spinal cord and brain barriers in health and disease. Elsevier Academic Press, San Diego, pp 231–298

    Google Scholar 

  22. Sharma HS (2004) Pathophysiology of the blood-spinal cord barrier in traumatic injury. In: Sharma HS, Westman J (eds) Blood-spinal cord and brain barriers in health and disease. Elsevier Academic Press, San Diego, pp 437–518

    Google Scholar 

  23. Sharma HS (2005) Pathophysiology of blood-spinal cord barrier in traumatic injury and repair. Curr Pharm Des 11: 1353–1389

    Article  PubMed  CAS  Google Scholar 

  24. Sharma HS, Westman J (2004) Blood-spinal cord and brain barriers in health and disease. Elsevier Academic Press, San Diego, pp 1–617

    Google Scholar 

  25. Sharma HS, Zimmer C, Westman J, Cervos-Navarro J (1992) Acute systemic heat stress increases glial fibrillary acidic protein immunoreactivity in brain: experimental observations in conscious normotensive young rats. Neuroscience 48: 889–901

    Article  PubMed  CAS  Google Scholar 

  26. Sharma HS, Olsson Y, Cervós-Navarro J (1993) p-Chlorophenylalanine, a serotonin synthesis inhibitor, reduces the response of glial fibrillary acidic protein induced by trauma to the spinal cord. An immunohistochemical investigation in the rat. Acta Neuropathol (Berl) 86: 422–427

    Article  PubMed  CAS  Google Scholar 

  27. Sharma HS, Alm P, Westman J (1998) Nitric oxide and carbon monoxide in the brain pathology of heat stress. Prog Brain Res 115: 297–333

    PubMed  CAS  Google Scholar 

  28. Sharma HS, Nyberg F, Westman J, Alm P, Gordh T, Lindholm D (1998) Brain derived neurotrophic factor and insulin like growth factor-1 attenuate upregulation of nitric oxide synthase and cell injury following trauma to the spinal cord. An immunohistochemical study in the rat. Amino Acids 14: 121–129

    Article  PubMed  Google Scholar 

  29. Sharma HS, Nyberg F, Gordh T, Alm P, Westman J (2000) Neurotrophic factors influence upregulation of constitutive isoform of heme oxygenase and cellular stress response in the spinal cord following trauma. An experimental study using immunohistochemistry in the rat. Amino Acids 19: 351–361

    Article  PubMed  CAS  Google Scholar 

  30. Sharma HS, Westman J, Gordh T, Alm P (2000) Topical application of brain derived neurotrophic factor influences upregulation of constitutive isoform of heme oxygenase in the spinal cord following trauma an experimental study using immunohistochemistry in the rat. Acta Neurochir [Suppl] 76: 365–369

    CAS  Google Scholar 

  31. Sharma HS, Badgaiyan RD, Mohanty S, Alm P, Wiklund L (2005) Neuroprotective effects of nitric oxide synthase inhibitors in spinal cord injury induced pathophysiology and motor functions. An experimental study in the rat. Ann NY Acad Sci 1053 (in press)

    Google Scholar 

  32. Sharma HS, Wiklund L, Badgaiyan RD, Mohanty S, Alm P (2006) Intracerebral administration of neuronal nitric oxide synthase antiserum attenuates traumatic brain injury induced blood-brain barrier permeability, brain edema and sensory motor disturbances in the rat. Acta Neurochir [Suppl] 96: 288–294

    Article  Google Scholar 

  33. Sharma HS, Nyberg F, Gordh T, Alm P (2006) Topical application of dynorphin A (1–17) antibodies attenuate neuronal nitric oxide synthase up-regulation, edema formation, and cell injury following a focal trauma to the rat spinal cord. Acta Neurochir [Suppl] 96: 309–315

    CAS  Google Scholar 

  34. Solodkin A, Traub RJ, Gebhart GF (1992) Unilateral hind-paw inflammation produces a bilateral increase in NADPH-diaphorase histochemical staining in the rat lumbar spinal cord. Neuroscience 51: 495–499

    Article  PubMed  CAS  Google Scholar 

  35. Tao-Cheng JH, Brightman MW (1988) Development of membrane interactions between brain endothelial cells and astrocytes in vitro. Int J Dev Neurosci 6: 25–37

    Article  PubMed  CAS  Google Scholar 

  36. Yamamoto T, Shimoyama N (1995) Role of nitric oxide in the development of thermal hyperesthesia induced by sciatic nerve constriction injury in the rat. Anesthesiology 82: 1266–1273

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Dept. of Surgical Sciences, Anesthesiology & Intensive Care Medicine, University Hospital, SE-75185, Uppsala, Sweden

    H. S. Sharma

  2. Laboratory of Pain Research, Department of Surgical Sciences, Anesthesiology and Intensive Care Medicine, University Hospital, Uppsala University, Uppsala, Sweden

    T. Gordh & H. S. Sharma

Authors
  1. T. Gordh
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  2. H. S. Sharma
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Editor information

Editors and Affiliations

  1. Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA

    Julian T. Hoff , Richard F. Keep , Guohua Xi  & Ya Hua , ,  & 

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© 2006 Springer-Verlag

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Gordh, T., Sharma, H.S. (2006). Chronic spinal nerve ligation induces microvascular permeability disturbances, astrocytic reaction, and structural changes in the rat spinal cord. In: Hoff, J.T., Keep, R.F., Xi, G., Hua, Y. (eds) Brain Edema XIII. Acta Neurochirurgica Supplementum, vol 96. Springer, Vienna. https://doi.org/10.1007/3-211-30714-1_70

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  • DOI: https://doi.org/10.1007/3-211-30714-1_70

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-30712-0

  • Online ISBN: 978-3-211-30714-4

  • eBook Packages: MedicineMedicine (R0)

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