DOXYCYCLINE TREATMENT REDUCES ISCHEMIC BRAIN-DAMAGE IN TRANSIENT MIDDLE CEREBRAL-ARTERY OCCLUSION IN THE RAT

Agents that inhibit leukocyte adhesion including intercellular adhesio n molecule-1 antibodies (anti-ICAM-1) have shown beneficial effects in experimental central nervous system (CNS) ischemia. Doxycycline inhib its leukocyte function in vitro by binding divalent cations and reduce s spinal cord reperfusion injury. The authors used a clinically releva nt model of focal CNS reperfusion injury to test whether treatment wit h doxycycline would reduce cerebral ischemic damage and improve functi onal outcome. Reversible middle cerebral artery occlusion was produced in adult Sprague-Dawley rats by advancing a filament into the interna l carotid artery for 2 h. Animals received either IP doxycycline (10 m g/kg) (N = 13) or saline (N = 11) 30 min before ischemia, followed by 10 mg/kg every 8 h x 6. Both functional assessment (5 point neurologic scale) and infarct volume was evaluated at 48 h. Functional efficacy: doxycycline 0.5 +/- 0.2 (mean +/-SE) vs control 1.3 +/- 0.3 (p = 0.03 ). Infarct volume: doxycycline 56 +/- 18 mm(3) vs control 158 +/- 44 m m(3) (p = 0.03); This protective effect supports the role of doxycycli ne in reducing CNS reperfusion injury.