Minocycline effectively protects the rabbit's spinal cord from aortic occlusion-related Ischemia

Benjamin Drenger, Yakov Fellig, Dror Ben-David, Bella Mintz, Suhel Idrees, Omer Or, Leon Kaplan, Yehuda Ginosar, Yair Barzilay

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Objectives To identify the minocycline anti-inflammatory and antiapoptotic mechanisms through which it is believed to exert spinal cord protection during aortic occlusion in the rabbit model. Design An animal model of aortic occlusion-related spinal cord ischemia. Randomized study with a control group and pre-ischemia and post-ischemia escalating doses of minocycline to high-dose minocycline in the presence of either hyperglycemia, a pro-apoptotic maneuver, or wortmannin, a specific phosphatidylinositol 3-kinase antagonist. Setting Tertiary medical center and school of medicine laboratory. Participants Laboratory animals-rabbits. Interventions Balloon obstruction of infrarenal aorta introduced via femoral artery incision. Results Severe hindlimb paralysis (mean Tarlov score 0.36±0.81 out of 3) was observed in all the control group animals (9 of 11 with paraplegia and 2 of 11 with paraparesis) compared with 11 of 12 neurologically intact animals (mean Tarlov score 2.58±0.90 [p = 0.001 compared with control]) in the high-dose minocycline group. This protective effect was observed partially during a state of hyperglycemia and was completely abrogated by wortmannin. Minocycline administration resulted in higher neurologic scores (p = 0.003) and a shift to viable neurons and more apoptotic-stained nuclei resulting from reduced necrosis (p = 0.001). Conclusions In a rabbit model of infrarenal aortic occlusion, minocycline effectively reduced paraplegia by increasing the number of viable neurons in a dose-dependent manner. Its action was completely abrogated by inhibiting the phosphatidylinositol 3-kinase pathway and was inhibited partially by the pro-apoptotic hyperglycemia maneuver, indicating that the activation of cell salvage pathways and mitochondrial sites are possible targets of minocycline action in an ischemic spinal cord.

Original languageEnglish
Pages (from-to)282-290
Number of pages9
JournalJournal of Cardiothoracic and Vascular Anesthesia
Volume30
Issue number2
DOIs
StatePublished - Apr 1 2016
Externally publishedYes

Keywords

  • hyperglycemia
  • induced cord ischemia
  • minocycline
  • neuroprotection
  • phosphatidylinositol 3-kinase pathway rabbit model

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