Minocycline Effectively Protects the Rabbit's Spinal Cord From Aortic Occlusion-Related Ischemia.

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.

• Authors: Benjamin Drenger, Yakov Fellig, Dror Ben-David, Bella Mintz, Suhel Idrees, Omer Or, Leon Kaplan, Yehuda Ginosar, Yair Barzilay
• Journal: Journal of cardiothoracic and vascular anesthesia (J Cardiothorac Vasc Anesth) Vol. 30 Issue 2 Pg. 282-90 (Apr 2016) ISSN: 1532-8422 [Electronic] United States
• PMID: 26853309 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016. Published by Elsevier Inc.

Chemical References

• Androstadienes
• Anti-Inflammatory Agents
• Minocycline
• Wortmannin

Topics

• Androstadienes (pharmacology)
• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Aorta, Thoracic
• Apoptosis (drug effects)
• Balloon Occlusion (adverse effects)
• Dose-Response Relationship, Drug
• Femoral Artery (surgery)
• Hindlimb
• Male
• Minocycline (antagonists & inhibitors, therapeutic use)
• Neurons (drug effects)
• Paralysis (etiology, prevention & control)
• Rabbits
• Spinal Cord Ischemia (etiology, prevention & control)
• Wortmannin