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Cerebrolysin Attenuates Blood–Brain Barrier and Brain Pathology Following Whole Body Hyperthermia in the Rat

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Brain Edema XIV

Part of the book series: Acta Neurochirurgica Supplementum ((NEUROCHIRURGICA,volume 106))

Abstract

The possibility that Cerebrolysin, a mixture of several neurotrophic factors, has some neuroprotective effects on whole body hyperthermia (WBH) induced breakdown of the blood–brain barrier (BBB), blood–CSF barrier (BCSFB), brain edema formation and neuropathology were examined in a rat model. Rats subjected to a 4 h heat stress at 38°C in a biological oxygen demand (BOD) incubator exhibited profound increases in BBB and BCSFB permeability to Evans blue and radioiodine tracers compared to controls. Hippocampus, caudate nucleus, thalamus and hypothalamus exhibited pronounced increase in water content and brain pathology following 4 h heat stress. Pretreatment with Cerebrolysin (1, 2 or 5 mL/kg i.v.) 24 h before WBH significantly attenuated breakdown of the BBB or BCSFB and brain edema formation. This effect was dose dependent. Interestingly, the cell and tissue injury following WBH in cerebrolysin-treated groups were also considerably reduced. These novel observations suggest that cerebrolysin can attenuate WBH induced BBB and BCSFB damage resulting in neuroprotection.

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References

  1. Guo S, Kim WJ, Lok J, Lee SR, Besancon E, Luo BH, Stins MF, Wang X, Dedhar S, Lo EH (2008) Neuroprotection via matrix-trophic coupling between cerebral endothelial cells and neurons. Proc Natl Acad Sci USA. May 27;105(21):7582–7587

    Google Scholar 

  2. Kiyatkin EA, Brown PL, Sharma HS (2007) Brain edema and breakdown of the blood–brain barrier during methamphetamine intoxication: critical role of brain hyperthermia. Eur J Neurosci. Sep 26(5):1242–1253

    Article  Google Scholar 

  3. Milton AS (1989) Thermoregulatory actions of eicosanoids in the central nervous system with particular regard to the pathogenesis of fever. Ann NY Acad Sci 559:392–410. Review

    Google Scholar 

  4. Mitrasinovic OM, Grattan A, Robinson CC, Lapustea NB, Poon C, Ryan H, Phong C, Murphy GM Jr. (2005) Microglia overexpressing the macrophage colony-stimulating factor receptor are neuroprotective in a microglial–hippocampal organotypic coculture system. J Neurosci. Apr 27; 25(17):4442–4451

    Google Scholar 

  5. Schwab ME, Bartholdi D (1996) Degeneration and regeneration of axons in the lesioned spinal cord. Physiol Rev. Apr; 76(2):319–370. Review

    Google Scholar 

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

    Chapter  Google Scholar 

  7. Sharma H S. (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. May 15; 830:1–94

    Google Scholar 

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

    Google Scholar 

  9. Sharma HS (2003) Neurotrophic factors attenuate microvascular permeability disturbances and axonal injury following trauma to the rat spinal cord. Acta Neurochir Suppl 86:383–388

    Article  PubMed  CAS  Google Scholar 

  10. Sharma HS (2006) Post-traumatic application of brain-derived neurotrophic factor and glia-derived neurotrophic factor on the rat spinal cord enhances neuroprotection and improves motor function. Acta Neurochir Suppl 96:329–334

    Article  PubMed  CAS  Google Scholar 

  11. Sharma HS (2006) Hyperthermia induced brain oedema: current status and future perspectives. Indian J Med Res. May 123(5):629–652. Review

    Google Scholar 

  12. Sharma HS (2006) Hyperthermia influences excitatory and inhibitory amino acid neurotransmitters in the central nervous system. An experimental study in the rat using behavioural, biochemical, pharmacological, and morphological approaches. J Neural Transm. Apr 113(4):497–519

    Google Scholar 

  13. Sharma HS (2007) Neurotrophic factors in combination: a possible new therapeutic strategy to influence pathophysiology of spinal cord injury and repair mechanisms. Curr Pharm Des 13(18):1841–1874. Review

    Google Scholar 

  14. Sharma HS (2007) Methods to produce hyperthermia-induced brain dysfunction. Prog Brain Res 162:173–99. Review

    Google Scholar 

  15. Sharma HS (2007) A select combination of neurotrophins enhances neuroprotection and functional recovery following spinal cord injury. Ann NY Acad Sci Dec 1122:95–111

    Article  Google Scholar 

  16. Sharma HS, Hoopes PJ (2003) Hyperthermia induced pathophysiology of the central nervous system. Int J Hyperthermia. May–Jun 19(3):325–354. Review

    Google Scholar 

  17. Sharma HS, Ali SF (2006) Alterations in blood–brain barrier function by morphine and methamphetamine. Ann NY Acad Sci. Aug 1074:198–224

    Article  CAS  Google Scholar 

  18. Sharma HS, Cervós-Navarro J (1990) Brain oedema and cellular changes induced by acute heat stress in young rats. Acta Neurochir Suppl (Wien) 51:383–386

    CAS  Google Scholar 

  19. Sharma HS, Dey PK (1986) Probable involvement of 5-hydroxytryptamine in increased permeability of blood–brain barrier under heat stress in young rats. Neuropharmacology. Feb 25(2):161–167

    Article  CAS  Google Scholar 

  20. Sharma HS, Johanson CE (2007) Intracerebroventricularly administered neurotrophins attenuate blood cerebrospinal fluid barrier breakdown and brain pathology following whole-body hyperthermia: an experimental study in the rat using biochemical and morphological approaches. Ann NY Acad Sci. Dec 1122:112–129

    Article  CAS  Google Scholar 

  21. Sharma HS, Westman J (1998) Brain functions in hot environment, progress in brain research, 115. Elsevier, Amsterdam, pp 1–516

    Google Scholar 

  22. Sharma HS, Westman J, Nyberg F (1998) Pathophysiology of brain edema and cell changes following hyperthermic brain injury. Prog Brain Res 115:351–412. Review

    Google Scholar 

  23. Wahl M, Unterberg A, Baethmann A, Schilling L (1988) Mediators of blood–brain barrier dysfunction and formation of vasogenic brain edema. J Cereb Blood Flow Metab. Oct 8(5):621–634. Review

    Google Scholar 

  24. Winkler T, Sharma HS, Stålberg E, Badgaiyan RD (2000) Neurotrophic factors attenuate alterations in spinal cord evoked potentials and edema formation following trauma to the rat spinal cord. Acta Neurochir Suppl 76:291–296

    PubMed  CAS  Google Scholar 

  25. Winkler T, Sharma HS, Stålberg E, Westman J (1998) Spinal cord bioelectrical activity, edema and cell injury following a focal trauma to the spinal cord. An experimental study using pharmacological and morphological approach. In: Stålberg E, Sharma HS, Olsson Y (eds) Spinal cord monitoring. Springer Wien, New York, pp 281–348

    Google Scholar 

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Acknowledgements

This study is supported by Grants from Swedish Medical Research Council, Stockholm (HSS 02710); National Institute of Health (R01 AG 027910, CEJ), USA; Alexander von Humboldt Foundation (HSS), Germany; Astra Zeneca Mölndal, Sweden (HSS); Society for the study on Neuroplasticity and Neuroprotection (SSNN), Romania and Ebewe Pharma, Austria (HSS). Technical assistance of Kärstin Flink, Ingmarie Olsson, Margareta Butler, Inga Hörte, Mari-Anne Carlsson and Ulla Nilsson as well as the secretarial assistance of Angela Ludwig and Nancy Johanson are highly appreciated.

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Correspondence to Hari Shanker Sharma .

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Sharma, H.S., Zimmermann-Meinzingen, S., Sharma, A., Johanson, C.E. (2010). Cerebrolysin Attenuates Blood–Brain Barrier and Brain Pathology Following Whole Body Hyperthermia in the Rat. In: Czernicki, Z., Baethmann, A., Ito, U., Katayama, Y., Kuroiwa, T., Mendelow, D. (eds) Brain Edema XIV. Acta Neurochirurgica Supplementum, vol 106. Springer, Vienna. https://doi.org/10.1007/978-3-211-98811-4_60

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  • DOI: https://doi.org/10.1007/978-3-211-98811-4_60

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  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-98758-2

  • Online ISBN: 978-3-211-98811-4

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