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

39 Citations (Scopus)

Abstract

Background and Purpose: Activated leukocytes appear to potentiate central nervous system reperfusion injury, and agents that block leukocyte adhesion have shown neuroprotective efficacy in experimental models. Doxycycline, a tetracycline 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)1411-1416
Number of pages6
JournalStroke
Volume25
Issue number7
StatePublished - Jul 1994
Externally publishedYes

Fingerprint

Nervous System Trauma
Doxycycline
Reperfusion Injury
Central Nervous System
Rabbits
Leukocytes
Ischemia
Spinal Cord Ischemia
Control Groups
Paraplegia
Divalent Cations
Tetracycline
Leukocyte Count
Spinal Cord
Theoretical Models
Phosphates
Anti-Bacterial Agents

Keywords

  • cerebral ischemia
  • doxycycline
  • leukocytes
  • reperfusion

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

Clark, W. M., Calcagno, F. A., Gabler, W. L., Smith, J. R., & Coull, B. M. (1994). Reduction of central nervous system reperfusion injury in rabbits using doxycycline treatment. Stroke, 25(7), 1411-1416.

Reduction of central nervous system reperfusion injury in rabbits using doxycycline treatment. / Clark, Wayne M.; Calcagno, Frank A.; Gabler, Walter L.; Smith, John R.; Coull, Bruce M.

In: Stroke, Vol. 25, No. 7, 07.1994, p. 1411-1416.

Research output: Contribution to journalArticle

Clark, WM, Calcagno, FA, Gabler, WL, Smith, JR & Coull, BM 1994, 'Reduction of central nervous system reperfusion injury in rabbits using doxycycline treatment', Stroke, vol. 25, no. 7, pp. 1411-1416.
Clark WM, Calcagno FA, Gabler WL, Smith JR, Coull BM. Reduction of central nervous system reperfusion injury in rabbits using doxycycline treatment. Stroke. 1994 Jul;25(7):1411-1416.
Clark, Wayne M. ; Calcagno, Frank A. ; Gabler, Walter L. ; Smith, John R. ; Coull, Bruce M. / Reduction of central nervous system reperfusion injury in rabbits using doxycycline treatment. In: Stroke. 1994 ; Vol. 25, No. 7. pp. 1411-1416.
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