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Zinc protoporphyrin IX attenuates closed head injury-induced edema formation, blood-brain barrier disruption, and serotonin levels in the rat

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Brain Edema XIII

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

Summary

The role of heme oxygenase (HO) in closed head injury (CHI) was examined using a potent HO and guanylyl cyclase inhibitor, zinc protoporphyrin (Zn-PP) in the rat. Blood-brain barrier (BBB) permeability to Evans blue and radioiodine, edema formation, and plasma and brain levels of serotonin were measured in control, CHI, and Zn-PP-treated CHI rats. CHI was produced by an impact of 0.224 N on the right parietal bone by dropping 114.6 g weight from a height of 20 cm in anesthetized rats. This concussive injury resulted in edema formation and brain swelling 5 hours after insult that was most pronounced in the contralateral hemisphere. The whole brain was edematous and remained in a semi-fluid state. Microvascular permeability disturbances to protein tracers were prominent in both cerebral hemispheres and the underlying cerebral structures. Plasma and brain serotonin showed pronounced increases and correlated with edema formation. Pretreatment with Zn-PP (10 mg/ kg, i.p) 30 minutes before or after CHI attenuated edema formation, brain swelling, plasma and brain serotonin levels, and microvascular permeability at 5 hours. Brain edema, BBB permeability, and serotonin levels were not attenuated when the compound was administered 60 minutes post-CHI suggesting that HO is involved in cellular and molecular mechanisms of edema formation and BBB breakdown early after CHI.

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References

  1. Alm P, Sharma HS, Sjöquist PO, Westman J (2000) A new antioxidant compound H-290/51 attenuates nitric oxide synthase and heme oxygenase expression following hyperthermic brain injury. An experimental study using immunohistochemistry in the rat. Amino Acids 19: 383–394

    Article  PubMed  CAS  Google Scholar 

  2. Bergemalm PO, Lyxell B (2005) Appearances are deceptive? Long-term cognitive and central auditory sequelae from closed head injury. Int J Audiol 44: 39–49

    PubMed  Google Scholar 

  3. Blumenthal SB, Kiemer AK, Tiegs G, Seyfried S, Holtje M, Brandt B, Holtje HD, Zahler S, Vollmar AM (2005) Metalloporphyrins inactivate caspase-3 and-8. FASEB J 19: 1272–1279

    Article  PubMed  CAS  Google Scholar 

  4. Chieregato A, Fainardi E, Morselli-Labate AM, Antonelli V, Compagnone C, Targa L, Kraus J, Servadei F (2005) Factors associated with neurological outcome and lesion progression in traumatic subarachnoid hemorrhage patients. Neurosurgery 56: 671–680

    Article  PubMed  Google Scholar 

  5. Dey PK, Sharma HS (1984) Influence of ambient temperature and drug treatments on brain oedema induced by impact injury on skull in rats. Indian J Physiol Pharmacol 28: 177–186

    PubMed  CAS  Google Scholar 

  6. Farin A, Marshall LF (2004) Lessons from epidemiologic studies in clinical trials of traumatic brain injury. Acta Neurochir [Suppl] 89: 101–107

    CAS  Google Scholar 

  7. Fortin S, Godbout L, Braun CM (2003) Cognitive structure of executive deficits in frontally lesioned head trauma patients performing activities of daily living. Cortex 39: 273–291

    PubMed  Google Scholar 

  8. 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 

  9. Heitger MH, Macaskill MR, Jones RD, Anderson TJ (2005) The impact of mild closed head injury on involuntary saccadic adaptation: evidence for the preservation of implicit motor learning. Brain Inj 19: 109–117

    PubMed  Google Scholar 

  10. Hlatky R, Valadka AB, Goodman JC, Robertson CS (2004) Evolution of brain tissue injury after evacuation of acute traumatic subdural hematomas. Neurosurgery 55: 1318–1323

    Article  PubMed  Google Scholar 

  11. Kadoya C, Domino EF, Yang GY, Stern JD, Betz AL (1995) Preischemic but not postischemic zinc protoporphyrin treatment reduces infarct size and edema accumulation after temporary focal cerebral ischemia in rats. Stroke 26: 1035–1038

    PubMed  CAS  Google Scholar 

  12. Leffler CW, Balabanova L, Fedinec AL, Parfenova H (2005) Nitric oxide increases carbon monoxide production by piglet cerebral microvessels. Am J Physiol Heart Circ Physiol [Epub ahead of print]

    Google Scholar 

  13. Levere RD, Escalante B, Schwartzman ML, Abraham NG (1989) Role of heme oxygenase in heme-mediated inhibition of rat brain Na+-K+-ATPase: protection by tin-protoporphyrin. Neurochem Res 14: 861–864

    Article  PubMed  CAS  Google Scholar 

  14. Maines MD (1988) Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J 2: 2557–2568

    PubMed  CAS  Google Scholar 

  15. Marshall RS (2004) The functional relevance of cerebral hemodynamics: why blood flow matters to the injured and recovering brain. Curr Opin Neurol 17: 705–709

    Article  PubMed  Google Scholar 

  16. Nolan S (2005) Traumatic brain injury: a review. Crit Care Nurs Q 28: 188–194

    PubMed  Google Scholar 

  17. Panizzon KL, Dwyer BE, Nishimura RN, Wallis RA (1996) Neuroprotection against CA1 injury with metalloporphyrins. Neuroreport 7: 662–666

    Article  PubMed  CAS  Google Scholar 

  18. Ratcliff G, Colantonio A, Escobar M, Chase S, Vernich L (2005) Long-term survival following traumatic brain injury. Disabil Rehabil 27: 305–314

    PubMed  Google Scholar 

  19. Schmidt OI, Heyde CE, Ertel W, Stahel PF (2005) Closed head injury — an inflammatory disease? Brain Res Brain Res Rev 48: 388–399

    Article  PubMed  Google Scholar 

  20. Serfass L, Burstyn JN (1998) Effect of heme oxygenase inhibitors on soluble guanylyl cyclase activity. Arch Biochem Biophys 359: 8–16

    Article  PubMed  CAS  Google Scholar 

  21. Sharma HS, Westman J (1998) Brain Functions in Hot Environment. Elsevier, Amsterdam, pp 1–516

    Google Scholar 

  22. Sharma HS (1999) Pathophysiology of blood-brain barrier, brain edema and cell injury following hyperthermia: New role of heat shock protein, nitric oxide and carbon monoxide. An experimental study in the rat using light and electron microscopy. Acta Universitatis Upsaliensis 830: 1–94

    Google Scholar 

  23. Sharma HS (2000) Degeneration and regeneration in the CNS. New roles of heat shock proteins, nitric oxide and carbon monoxide. Amino Acids 19: 335–337

    Article  PubMed  CAS  Google Scholar 

  24. 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 

  25. Sharma HS, Westman J (2003) Depletion of endogenous serotonin synthesis with p-CPA, attenuates upregulation of constitutive isoform of heme oxygenase-2 expression, edema formation and cell injury following a focal trauma to the rat spinal cord. Acta Neurochir Suppl 86: 389–394

    PubMed  CAS  Google Scholar 

  26. Sharma HS, Westman J (2004) The heat shock proteins and heme oxygenase response in central nervous system injuries. In: Sharma HS, Westman J (eds) Blood-spinal cord and brain barriers in health and disease. Elsevier Academic Press, San Diego, pp 329–360

    Google Scholar 

  27. Sharma HS, Alm P, Westman J (1997) Upregulation of hemeoxygenase-II in the rat spinal cord following heat stress. In: Nielsen-Johanssen B, Nielsen R (eds) Thermal physiology 1997. The August Krogh Institute, Copenhagen, pp 135–138

    Google Scholar 

  28. 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

    Article  PubMed  CAS  Google Scholar 

  29. Sharma HS, Drieu K, Alm P, Westman J (1999) Upregulation of neuronal nitric oxide synthase, edema and cell injury following heat stress are reduced by pretreatment with EGB-761 in the rat. J Therm Biol 24: 439–446

    Article  CAS  Google Scholar 

  30. Sharma HS, Alm P, Sjöquist PO, Westman J (2000) A new antioxidant compound H-290/51 attenuates upregulation of constitutive isoform of heme oxygenase (HO-2) following trauma to the rat spinal cord. Acta Neurochir [Suppl] 76: 153–157

    CAS  Google Scholar 

  31. 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 

  32. 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 

  33. Sharma HS, Drieu K, Westman J (2003) Antioxidant compounds EGB-761 and BN-52021 attenuate brain edema formation and hemeoxygenase expression following hyperthermic brain injury in the rat. Acta Neurochir [Suppl] 86: 313–319

    CAS  Google Scholar 

  34. Sharma HS, Sjöquist PO, Alm P (2003) A new antioxidant compound H-290/51 attenuates spinal cord injury induced expression of constitutive and inducible isoforms of nitric oxide synthase and edema formation in the rat. Acta Neurochir [Suppl] 86: 415–420

    CAS  Google Scholar 

  35. 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 

  36. Tavazzi B, Signoretti S, Lazzarino G, Amorini AM, Delfini R, Cimatti M, Marmarou A, Vagnozzi R (2005) Cerebral oxidative stress and depression of energy metabolism correlate with severity of diffuse brain injury in rats. Neurosurgery 56: 582–589

    Article  PubMed  Google Scholar 

  37. Verma A, Hirsch DJ, Glatt CE, Ronnett GV, Snyder SH (1993) Carbon monoxide: a putative neural messenger. Science 259: 381–384

    PubMed  CAS  Google Scholar 

  38. Vreman HJ, Stevenson DK (1988) Heme oxygenase activity as measured by carbon monoxide production. Anal Biochem 168: 31–38

    Article  PubMed  CAS  Google Scholar 

  39. Wagner KR, Hua Y, de Courten-Myers GM, Broderick JP, Nishimura RN, Lu SY, Dwyer BE (2000) Tin-mesoporphyrin, a potent heme oxygenase inhibitor, for treatment of intracerebral hemorrhage: in vivo and in vitro studies. Cell Mol Biol (Noisy-le-grand) 46: 597–608

    PubMed  CAS  Google Scholar 

  40. Zohar O, Schreiber S, Getslev V, Schwartz JP, Mullins PG, Pick CG (2003) Closed-head minimal traumatic brain injury produces long-term cognitive deficits in mice. Neuroscience 118: 949–955

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

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

    H. S. Sharma

  2. Laboratory of Neuroanatomy, Department of Medical Cell Biology, Biomedical Center, Uppsala University, Uppsala, Sweden

    P. Vannemreddy & H. S. Sharma

  3. Department of Surgical Sciences, Anesthesiology and Intensive Care, University Hospital, Uppsala University, Uppsala, Sweden

    A. K. Ray, R. Patnaik & H. S. Sharma

  4. Department of Biomedical Engineering, Institute of Technology, Banaras Hindu University, Varanasi, India

    A. K. Ray & R. Patnaik

  5. Department of Pharmacy, Institute of Technology, Banaras Hindu University, Varanasi, India

    S. Patnaik

  6. Department of Neurosurgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

    S. Mohanty

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  1. P. Vannemreddy
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  4. S. Patnaik
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  5. S. Mohanty
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  6. 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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Vannemreddy, P., Ray, A.K., Patnaik, R., Patnaik, S., Mohanty, S., Sharma, H.S. (2006). Zinc protoporphyrin IX attenuates closed head injury-induced edema formation, blood-brain barrier disruption, and serotonin levels in the rat. 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_34

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  • DOI: https://doi.org/10.1007/3-211-30714-1_34

  • 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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