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Minocycline Attenuates Brain Edema, Brain Atrophy and Neurological Deficits After Intracerebral Hemorrhage

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Brain Edema XIV

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

Abstract

Evidence suggests that microglia activation contributes to brain injury after intracerebral hemorrhage (ICH). The present study aimed to determine if minocycline, an inhibitor of microglia activation, can reduce brain edema, brain atrophy and neurological deficits after ICH.

Male Sprague-Dawley rats received an infusion of 100-µL autologous whole blood into the right basal ganglia. Rats received minocycline or vehicle treatment. There were two sets of experiments in this study. In the first set of experiments, the effects of minocycline on ICH-induced brain edema were examined at day 3. In the second set, behavioral tests were performed at days 1, 3, 7, 14 and 28. Rats were killed at day 28 for brain atrophy measurement (caudate and lateral ventricle size).

Minocycline reduced perihematomal brain edema in the ipsilateral basal ganglia (78.8 ± 0.4 vs. 80.9 ± 1.1% in the vehicle-treated group, p < 0.01). Minocycline also improved functional outcome. In addition, minocycline reduced brain tissue loss in the ipsilateral caudate (p < 0.01) and ventricular enlargement (p < 0.05).

In conclusion, minocycline attenuates ICH-induced brain edema formation, neurological deficits and brain atrophy in rats suggesting an important role of microglia in ICH-related brain injury.

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References

  1. Felberg RA, Grotta JC, Shirzadi AL, Strong R, Narayana P, Hill-Felberg SJ, Aronowski J (2002) Cell death in experimental intracerebral hemorrhage: the “black hole” model of hemorrhagic damage. Ann Neurol 51:517–524

    Article  PubMed  Google Scholar 

  2. Gong C, Hoff JT, Keep RF (2000) Acute inflammatory reaction following experimental intracerebral hemorrhage. Brain Res 871(1):57–65

    Article  PubMed  CAS  Google Scholar 

  3. Gong Y, Hua Y, Keep RF, Hoff JT, Xi G (2004) Intracerebral hemorrhage: effects of aging on brain edema and neurological deficits. Stroke 35:2571–2575

    Article  PubMed  Google Scholar 

  4. Hua Y, Schallert T, Keep RF, Wu J, Hoff JT, Xi G (2002) Behavioral tests after intracerebral hemorrhage in the rat. Stroke 33:2478–2484

    Article  PubMed  Google Scholar 

  5. Jenkins A, Maxwell W, Graham D (1989) Experimental intracerebral hematoma in the rat: sequential light microscopic changes. Neuropathol Appl Neurobiol 15:477–486

    Article  PubMed  CAS  Google Scholar 

  6. Klegeris A, McGeer PL (2000) Interaction of various intracellular signaling mechanisms involved in mononuclear phagocyte toxicity toward neuronal cells. J Leukocyte Biol 67:127–133

    PubMed  CAS  Google Scholar 

  7. Klein NC, Cunha BA (1995) Tetracyclines. Med Clin North America 79:789–801

    CAS  Google Scholar 

  8. Power C, Henry S, Del Bigio MR, Larsen PH, Corbett D, Imai Y, Yong VW, Peeling J (2003) Intracerebral hemorrhage induces macrophage activation and matrix metalloproteinases. Ann Neurol 53:731–742

    Article  PubMed  CAS  Google Scholar 

  9. Streit WJ, Sparks DL (1997) Activation of microglia in the brains of humans with heart disease and hypercholesterolemic rabbits. J Mol Med 75:130–138

    Article  PubMed  CAS  Google Scholar 

  10. Streit WJ, Walter SA, Pennell NA (1999) Reactive microgliosis. Prog Neurobiol 57:563–581

    Article  PubMed  CAS  Google Scholar 

  11. Suo Z, Wu M, Ameenuddin S, Anderson HE, Zoloty JE, Citron BA, Andrade-Gordon P, Festoff BW (2002) Participation of protease-activated receptor-1 in thrombin-induced microglial activation. J Neurochem 80:655–666

    Article  PubMed  CAS  Google Scholar 

  12. Tikka T, Fiebich BL, Goldsteins G, Keinanen R, Koistinaho J (2001) Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci 21:2580–2588

    PubMed  CAS  Google Scholar 

  13. Tikka TM, Koistinaho JE (2001) Minocycline provides neuroprotection against N-methyl-d-aspartate neurotoxicity by inhibiting microglia. J Immunol 166:7527–7533

    PubMed  CAS  Google Scholar 

  14. Wang J, Rogove AD, Tsirka AE, Tsirka SE (2003) Protective role of tuftsin fragment 1–3 in an animal model of intracerebral hemorrhage. Ann Neurol 54:655–664

    Article  PubMed  CAS  Google Scholar 

  15. Wang J, Tsirka SE (2005) Tuftsin fragment 1–3 is beneficial when delivered after the induction of intracerebral hemorrhage. Stroke 36:613–618

    Article  PubMed  CAS  Google Scholar 

  16. Wasserman JK, Schlichter LC (2007) Neuron death and inflammation in a rat model of intracerebral hemorrhage: effects of delayed minocycline treatment. Brain Res 1136:208–218

    Article  PubMed  CAS  Google Scholar 

  17. Xi G, Keep RF, Hoff JT (2006) Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol 5:53–63

    Article  PubMed  Google Scholar 

  18. Yang S, Nakamura T, Hua Y, Keep RF, Younger JG, He Y, Hoff JT, Xi G (2006) The role of complement C3 in intracerebral hemorrhage-induced brain injury. J Cereb Blood Flow Metab 26:1490–1495

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by grants NS-017760, NS-039866, and NS-047245 from the National Institutes of Health (NIH), 0755717Z from American Heart Association (AHA), and NSFC30600195 from National Natural Science Foundation of China (NSFC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, AHA, or NSFC.

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Correspondence to G. Xi .

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Wu, J., Yang, S., Hua, Y., Liu, W., Keep, R.F., Xi, G. (2010). Minocycline Attenuates Brain Edema, Brain Atrophy and Neurological Deficits After Intracerebral Hemorrhage. 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_26

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  • DOI: https://doi.org/10.1007/978-3-211-98811-4_26

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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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