Protection of Minocycline on Early Brain Injury After Subarachnoid Hemorrhage in Rats

  • Zong-duo Guo
  • Hai-tao Wu
  • Xiao-chuan Sun
  • Xiao-dong Zhang
  • John H. Zhang
Part of the Acta Neurochirurgica Supplements book series (NEUROCHIRURGICA, volume 110/1)


Minocycline has been shown to be neuroprotective in cerebral ischemia and in other models of brain injury. Our goal is to observe the protection of minocycline on EBI after SAH and the mechanism. 48 adult male SD rats were randomly divided into four groups: the sham-operated group, SAH group, vehicle group (SAH + normal sodium), and minocycline group (SAH + minocycline). The SAH model was induced by injecting 300 μl of autologous arterial blood into the prechiasmatic cistern. Expressions of MMP-9 in the hippocampus were examined at 24 h by western blot and zymography. Western blot and zymography showed that the expression of total and active MMP-9 increased dramatically at 24 h after SAH compared with that of the sham group (P < 0.01). The clinical assessments got a lower score than that of the sham-operated group. After treated with minocycline, the expression of MMP-9 decreased significantly (P < 0.01 vs. vehicle group), and the clinical assessments improved. We conclude that minocycline can protect EBI after SAH, which may be related to the mechanism of inhibiting the expression of MMP-9 in the hippocampus.


Early brain injury Matrix metalloproteinase 9 Minocycline Subarachnoid hemorrhage 


  1. 1.
    Schievink WI, Riedinger M, Jhutty TK, Simon P. Racial disparities in subarachnoid hemorrhage mortality: Los Angeles County, California, 1985–1998. Neuroepidemiology 2004;23:299–305.PubMedCrossRefGoogle Scholar
  2. 2.
    Pluta RM, Hansen-Schwartz J, Dreier J, Vajkoczy P, Macdonald RL, Nishizawa S, et al. Cerebral vasospasm following subarachnoid hemorrhage: time for a new world of thought. Neurol Res. 2009;31:151–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Guo Z, Sun X, He Z, Jiang Y, Zhang X, Zhang JH. Matrix metalloproteinase-9 potentiates early brain injury after subarachnoid hemorrhage. Neurol Res. 2009;15:2.Google Scholar
  4. 4.
    Zemke D, Majid A. The potential of minocycline for neuroprotection in human neurologic disease. Clin Neuropharmacol. 2004;27:293–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Lee CZ, Xue Z, Zhu Y, Yang GY, Young WL. Matrix metalloproteinase-9 inhibition attenuates vascular endothelial growth factor-induced intracerebral hemorrhage. Stroke 2007;38:2563–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Sutton TA, Kelly KJ, Mang HE, Plotkin Z, Sandoval RM, Dagher PC. Minocycline reduces renal microvascular leakage in a rat model of ischemic renal injury. Am J Physiol Renal Physiol. 2005;288:F91–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Prunell GF, Mathiesen T, Diemer NH, Svendgaard NA. Experimental subarachnoid hemorrhage: subarachnoid blood volume, mortality rate, neuronal death, cerebral blood flow, and perfusion pressure in three different rat models. Neurosurgery 2003;52:165–75; discussion 175–166.PubMedGoogle Scholar
  8. 8.
    Yamaguchi M, Zhou C, Nanda A, Zhang JH. Ras protein contributes to cerebral vasospasm in a canine double-hemorrhage model. Stroke 2004;35:1750–5.PubMedCrossRefGoogle Scholar
  9. 9.
    Kawakita K, Kawai N, Kuroda Y, Yasashita S, Nagao S. Expression of matrix metalloproteinase-9 in thrombin-induced brain edema formation in rats. J Stroke Cerebrovasc Dis. 2006;15:88–95.PubMedCrossRefGoogle Scholar
  10. 10.
    Sifringer M, Stefovska V, Zentner I, Hansen B, Stepulak A, Knaute C, et al. The role of matrix metalloproteinases in infant traumatic brain injury. Neurobiol Dis. 2007;25:526–35.PubMedCrossRefGoogle Scholar
  11. 11.
    Vikman P, Beg S, Khurana TS, Hansen-Schwartz J, Edvinsson L. Gene expression and molecular changes in cerebral arteries following subarachnoid hemorrhage in the rat. J Neurosurg. 2006;105:438–44.PubMedCrossRefGoogle Scholar
  12. 12.
    Sehba FA, Mostafa G, Knopman J, Friedrich V Jr, Bederson JB. Acute alterations in microvascular basal lamina after subarachnoid hemorrhage. J Neurosurg. 2004;101:633–40.PubMedCrossRefGoogle Scholar
  13. 13.
    Lee SR, Tsuji K, Lo EH. Role of matrix metalloproteinases in delayed neuronal damage after transient global cerebral ischemia. J Neurosci. 2004;24:671–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Copin JC, Gasche Y. Matrix metalloproteinase-9 deficiency has no effect on glial scar formation after transient focal cerebral ischemia in mouse. Brain Res. 2007;1150:167–73.PubMedCrossRefGoogle Scholar
  15. 15.
    Nagel S, Su Y, Horstmann S, Heiland S, Gardner H, Koziol J, et al. Minocycline and hypothermia for reperfusion injury after focal cerebral ischemia in the rat: effects on BBB breakdown and MMP expression in the acute and subacute phase. Brain Res. 2008;1188:198–206.PubMedCrossRefGoogle Scholar
  16. 16.
    Machado LS, Kozak A, Ergul A, Hess DC, Borlongan CV, Fagan SC. Delayed minocycline inhibits ischemia-activated matrix metalloproteinases 2 and 9 after experimental stroke. BMC Neurosci. 2006;7:56.PubMedCrossRefGoogle Scholar
  17. 17.
    Stirling DP, Koochesfahani KM, Steeves JD, Tetzlaff W. Minocycline as a neuroprotective agent. Neuroscientist 2005;11:308–22.PubMedCrossRefGoogle Scholar
  18. 18.
    Xu L, Fagan SC, Waller JL, Edwards D, Borlongan CV, Zheng J, et al. Low dose intravenous minocycline is neuroprotective after middle cerebral artery occlusion-reperfusion in rats. BMC Neurol. 2004;4:7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag/Wien 2011

Authors and Affiliations

  • Zong-duo Guo
    • 1
  • Hai-tao Wu
    • 1
  • Xiao-chuan Sun
    • 1
  • Xiao-dong Zhang
    • 1
  • John H. Zhang
    • 2
  1. 1.Department of NeurosurgeryFirst Hospital of Chongqing Medical UniversityChongqingPeople’s Republic of China
  2. 2.Department of NeurosurgeryLoma Linda University Medical CenterLoma LindaUSA

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