Minocycline and intracerebral hemorrhage: influence of injury severity and delay to treatment

Intracerebral hemorrhage (ICH) is a devastating condition currently lacking a defined line of treatment. The inflammatory response that ensues following its onset is thought to contribute to secondary injury following ICH, making inflammation a potential therapeutic target. Minocycline (MC), a commonly used antibiotic that also has anti-inflammatory and anti-apoptotic properties, provides histological protection in several animal stroke models when given soon after injury. However, its ability to provide protection with more clinically relevant delays is unknown. The objective of this study was to examine the effects of MC on histopathological changes and long-term functional outcomes in a collagenase-induced ICH model in rats when drug administration was delayed 3 h following the onset of ICH. In accordance with other studies, MC suppressed microglial/macrophage activation in the peri-infarct region at 5 days based on B4 isolectin histochemistry. However, no reduction in infarct volume was detected at 5 or 28 days post-ICH. Minocycline given for either 5 or 14 days also provided no functional benefit as assessed with a battery of sensory-motor tests (i.e., staircase, cylinder, ladder tests). These findings raise questions about the ability of MC to provide protection in ICH when delay to treatment is increased.