Abstracts

Rationale: Minocycline is a broad spectrum tetracycline derived antibiotic with anti-inflammatory properties. Recent research demonstrated that minocycline could be used as a neuroprotective agent to stop the progression of neurodegenerative diseases or after stroke. Here we examined whether minocycline could ameliorate weight loss and diminish cerebral damage of rats submitted to Status Epilepticus (SE) induced by pilocarpine. Methods: Adult rats (220-250 g) were treated with methylscopolamine (2 mg/kg) 30 min before pilocarpine injection (320 mg/kg; i.p.). Control rats were injected with saline instead of pilocarpine. Ninety minutes after SE onset, or saline injection, rats received diazepam (10 mg/kg). Eight of the twelve SE animals were treated with minocycline (25 mg/kg) twenty minutes after diazepam. In the following four days half of these animals also received daily injections of minocycline (12.5 mg/kg) resulting in four groups: pilocarpine+minocycline once; pilocarpine+minocycline daily; pilocarpine and controls (n=4 in each group). All animals were weighed daily and sacrificed five days after SE for examination of the encephalons. Difference in group means was assessed with ANOVA. Results: A steep weight loss one day after treatment was observed in all groups (Figure), with pilocarpine only group differing from controls. Two days after treatment all weights of animals that underwent SE (pilo+mino once, pilo+mino daily and pilocarpine) differed from controls; and pilocarpine also differed from pilo+mino daily. Three days after treatment there were no difference among groups. Four and five days after treatment only pilocarpine-treated animals weight differed from controls. Multiple infarctions areas ranging in size from <1 mm to 2 mm were observed in hippocampus and bilaterally in cortex of half of the pilocarpine treated animals. One lesion of less than 1 mm was observed in one pilocarpine+minocycline once animal. Conclusions: Our results show that minocycline can rescue rats from weight loss and cerebral damage after pilocarpine-induced SE. This compound could be employed as a prophylaxis to protect against general health deterioration commonly observed after episodes of status epilepticus.