Reduction of central nervous system reperfusion injury in rabbits using doxycycline treatment

Wayne M. Clark, Frank A. Calcagno, Walter L. Gabler, John R. Smith, Bruce M. Coull

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Background and Purpose Activated leukocytes appear to potentiate central nervous system reperfusion injury, and agents that block leukocyte adhesion have shown neuroprotec-tive efficacy in experimental models. Doxycycline, a tetracy-cline antibiotic, inhibits leukocyte function in vitro, presumably through divalent cation binding. We used a model of focal central nervous system reperfusion injury to determine the efficacy of doxycycline treatment in preserving neurological function. Methods Rabbits randomly received 10 mg/kg IV doxycycline 30 minutes before ischemia (pretreatment group) or 45 minutes after ischemia (posttreatment group) or received phosphate-buffered saline vehicle (control group) followed by 10 mg/kg q 8 hours times two. The average length of reversible spinal cord ischemia required to produce paraplegia (P50) at 18 hours was calculated for each group. Results For the control group (n= 13), the P50 was 22.8±2.2 minutes;for the pretreatment group (n=14), 35.5±2.4 minutes (P<.01;t=3.8);and for the posttreatment group (n = 13), 31.4±4.2 minutes (not significant; t=1.6). Doxycycline also attenuated postischemic decreases in in vivo leukocyte counts and inhibited in vitro leukocyte adhesion. Therapeutic doxycycline levels at 24 hours were confirmed in the plasma and spinal cord. Conclusions This significant protective effect suggests that doxycycline, a safe and readily available agent, may play a role in reducing clinical central nervous system reperfusion injury.

Original languageEnglish (US)
Pages (from-to)1411-1415
Number of pages5
JournalStroke
Volume25
Issue number7
DOIs
StatePublished - Jul 1994
Externally publishedYes

Keywords

  • Cerebral ischemia
  • Doxycycline
  • Leukocytes
  • Reperfusion

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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