title: Minocycline Effectively Protects the Rabbit's Spinal Cord From Aortic Occlusion-Related Ischemia.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Tertiary medical center and school of medicine laboratory.
  
  
  METHODS
  Laboratory animals-rabbits.
  
  
  METHODS
  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.
authors: Department of Anesthesiology and Critical Care Medicine. Electronic address: drenger@huji.ac.il.
authors: Benjamin
authors: B
authors: Drenger
authors: Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Yakov
authors: Y
authors: Fellig
authors: Department of Orthopedic Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Dror
authors: D
authors: Ben-David
authors: Department of Anesthesiology and Critical Care Medicine.
authors: Bella
authors: B
authors: Mintz
authors: Department of Anesthesiology and Critical Care Medicine.
authors: Suhel
authors: S
authors: Idrees
authors: Department of Orthopedic Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Omer
authors: O
authors: Or
authors: Department of Orthopedic Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Leon
authors: L
authors: Kaplan
authors: Department of Anesthesiology and Critical Care Medicine.
authors: Yehuda
authors: Y
authors: Ginosar
authors: Department of Orthopedic Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Yair
authors: Y
authors: Barzilay
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001013:Aorta, Thoracic; D017209:Apoptosis / Q000187:drug effects; D021721:Balloon Occlusion / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005263:Femoral Artery / Q000601:surgery; D006614:Hindlimb; D008297:Male; D008911:Minocycline / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D009474:Neurons / Q000187:drug effects; D010243:Paralysis / Q000209:etiology / Q000517:prevention & control; D011817:Rabbits; D020760:Spinal Cord Ischemia / Q000209:etiology* / Q000517:prevention & control*; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D008911:Minocycline; D000077191:Wortmannin
keywords: hyperglycemia; induced cord ischemia; minocycline; neuroprotection; phosphatidylinositol 3-kinase pathway rabbit model