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Preservation of motor function after spinal cord ischemia and reperfusion injury through microglial inhibition

Phillip D Smith1, Marshall T Bell, Ferenc Puskas

  • 1Department of Surgery, Division of Cardiothoracic Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA. phillip.smith@ucdenver.edu

The Annals of Thoracic Surgery
|April 2, 2013
PubMed
Abstract

Insights

Minocycline treatment significantly preserved motor function in mice after spinal cord ischemia and reperfusion injury by inhibiting microglial activation. This suggests minocycline as a potential therapy to prevent paralysis following aortic procedures.

Area of Science:

  • Neuroscience
  • Immunology
  • Vascular Surgery

Background:

  • Paraplegia is a severe complication of thoracoabdominal aortic procedures, often caused by spinal cord ischemia and reperfusion injury (SCIR).
  • Current pharmacologic interventions are ineffective for SCIR, and underlying mechanisms remain poorly understood.
  • Microglia, the resident macrophages of the spinal cord, may significantly contribute to SCIR.

Purpose of the Study:

  • To investigate the role of microglial activation in SCIR.
  • To test the hypothesis that minocycline, an inhibitor of microglial activation, can attenuate SCIR and preserve motor function.

Main Methods:

  • Mature male C57Bl/6 mice underwent 4 minutes of thoracic aortic occlusion and reperfusion.
  • Minocycline was administered before and daily after ischemia; vehicle controls received no treatment.
  • Hind-limb motor function was assessed, and spinal cords were harvested for histological and immunological analysis.

Main Results:

  • Minocycline treatment significantly preserved hind-limb motor function compared to complete paralysis in untreated mice.
  • Immunofluorescence confirmed minocycline inhibited microglial activation (Iba-1 staining).
  • Minocycline-treated spinal cords showed reduced apoptosis compared to controls.

Conclusions:

  • Minocycline effectively limits microglial activation, correlating with preserved motor function after aortic cross-clamping.
  • These findings indicate that microglia play a functional role in SCIR.
  • Minocycline presents a potential pharmacological therapy and a target for preventing paraplegia after aortic interventions.

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