Minocycline: a potential drug therapy following intracerebral hemmorhage?

Abstract

Intracerebral hemorrhage (ICH) is a devastating condition currently lacking a defined line of treatment. An inflammatory response ensues following its onset, and it has been suggested that it contributes to secondary damage following ICH, making inflammation a potential therapeutic target. Minocycline (MC), a commonly used antibiotic, which also has anti-inflammatory properties, has shown promise as a histological protectant in a number of animal stroke models. However, evidence for its ability to meet clinically relevant end-points, such as lessening of functional deficits with a wide therapeutic time window is scarce. Thus the objective of this study was to examine the effects of MC on short-term histopathological changes and long-term functional outcomes in a collagenase induced ICH model in rats. Drug treatment was initiated 3 h following the onset of stroke via intraperitoneal injection. -- In accordance with other studies, MC suppressed microglial/macrophage reaction (marker of the inflammatory response) in the perilesion region at 5 days (given for 5 days). However, it did not lead to histological protection as assessed by the size of the infarct volumes at 5 or 28 days. Quantitative sensori-motor tests showed that MC, given for 5 days or 14 days, offered no functional benefit up to 28 days following stroke. A number of factors could account for the lack of therapeutic effect, such as the severity of injury produced and the mode of drug delivery. However, the data suggest that minocycline may have a short therapeutic window and thus limited clinical application after ICH.