rifampin and Brain-Ischemia

The blood-brain barrier possesses active transporters carrying brain-permeable xenobiotics back into the blood against concentration gradients. We demonstrate that multidrug resistance transporter (Mdr)-1 is upregulated on capillary endothelium after focal cerebral ischemia; moreover, Mdr-1 deactivation by pharmacological inhibition or genetic knockout preferably enhances the accumulation and efficacy of two neuroprotectants known as Mdr-1 substrates in the ischemic brain. We predict that Mdr-1 inhibition may greatly facilitate neuroprotective therapies.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Blood-Brain Barrier; Brain; Brain Ischemia; Capillaries; Cerebrovascular Circulation; Endothelium, Vascular; Enzyme Inhibitors; Immunosuppressive Agents; Mice; Mice, Knockout; Neuroprotective Agents; Quinolines; Rifampin; Tacrolimus

Rifampicin is an antibacterial agent that is widely used in tuberculosis and leprosy therapy. Interestingly, some experimental studies indicate that rifampicin acts as a hydroxyl radical scavenger and a glucocorticoid receptor activator. In this study, the neuroprotective effect of rifampicin was evaluated after transient and permanent focal cerebral ischemia. Anaesthetized male C57BL/6j mice were submitted to permanent or transient thread occlusion of the middle cerebral artery (MCA). Reperfusion in transient ischemia was initiated 30 min later by thread retraction. Rifampicin or vehicle were applied intraperitoneally before permanent or immediately after 30 min of transient ischemia. Later, 24 h after permanent or transient ischemia, animals were re-anesthetized and decapitated. Brain injury was evaluated by triphenyltetrazolium chloride staining (TTC), terminal transferase biotinylated-dUTP nick end labeling (TUNEL) and cresyl violet staining. A 20-mg/kg sample of rifampicin showed a significant neuroprotection after cerebral ischemia. The number of TUNEL-positive cells in the striatum, where disseminated tissue injury was observed, was also reduced by application of rifampicin as compared with vehicle-treated animals. The present report shows that administration of rifampicin efficiently reduces brain injury after permanent and transient focal cerebral ischemia in mice.

Topics: Animals; Brain Infarction; Brain Ischemia; Cell Count; Cell Survival; Dose-Response Relationship, Drug; Enzyme Inhibitors; In Situ Nick-End Labeling; Infarction, Middle Cerebral Artery; Laser-Doppler Flowmetry; Male; Mice; Mice, Inbred C57BL; Reperfusion; Reperfusion Injury; Rifampin; Tetrazolium Salts