Abstracts

Rationale: Minocycline (MINO) is a broad spectrum tetracycline derived antibiotic with anti-inflammatory properties. It has been shown that MINO could be used as a neuroprotective agent for the treatment of neurological diseases. We examined whether a single dose of MINO administered 2 h after pilocarpine-induced Status Epilepticus (SE) could diminish cerebral lesion and spontaneous recurrent seizures (SRS). Methods: Adult Sprague Dawley rats were treated with methylscopolamine (2 mg/kg) 30 min before pilocarpine (320 mg/kg) or saline i.p. injection (Control group). All rats were treated with diazepam (10 mg/kg) i.p. 90 min after SE onset. At 20 min after diazepam injection, rats received MINO 25 mg/kg i.p. (SE Mino group) or saline (SE group). In order to verify cerebral lesions a group of rats were transcardially perfused 5 days after SE induction. Brain sections were processed with Nissl and neuronal nuclei marker (NeuN). The number of NeuN positive cells was estimated using stereology in the piriform cortex (PC). For SRS assessment, rats were video-recorded for approximately 5h per day, beginning 1 week after SE until 30 days later. Results: Nissl stained sections showed that in SE rats, layer 2 was almost completely ablated in the central and posterior portions of the PC when compared to Control and SE Mino. Quantification of NeuN labeled cells showed a large neuronal loss in SE rats (n=4; 34,882 5,072; p<0.05) compared to Controls (n=4; 96,458 3,057) that was partially recovered in SE Mino rats (n=4; 54,015 17,920; p>0.05). The neuron loss was more robust in layer 2 of the central PC in SE rats (19,734 3,166; p<0.01) compared to Controls (64,843 1,554) and this loss was ameliorated in the SE Mino rats (35,125 12,664). The SE rats presented a decrease of layer 2 volume (0.39 0.05 mm3; p<0.05) compared to Controls (0.59 0.05 mm3), that was partially ameliorated by MINO (0.44 0.05 mm3). The analysis of SRS in rats (stage 3 or greater) showed that both SE groups (saline or Mino) presented similar SRS frequency (SE, n=6: 1,15 0,19 SRS/day; SE Mino, n=5: 1,56 0,33 SRS/day; p>