Doxycycline could aggravate the absence-like epileptic seizures via matrix metalloproteinase

What is it about?

Matrix metalloproteinases (MMPs) are known to be activated in the brain by epileptic seizures and elevated MMP-9 activity has been found in a genetic model of generalized absence epilepsy (Wistar Albino Glaxo Rijswijk/WAG/Rij rats). In this study we posed the question, whether MMP inhibitory dose of doxycycline (20 mg/kg) could affect the spike-wave-discharges (SWDs) of the WAG/Rij rat. We found that intraperitoneal (i.p.) administration of 20 mg/kg doxycycline significantly increased the incidence and duration of SWDs for 4 hours. As doxycycline has both MMP inhibitory and anti-inflammatory effects we also tested a lower dose of doxycycline (10 mg/kg, i.p.) and a selective broad-spectrum MMP inhibitor GM6001 (N-[2(R)-2-(hydroxamido carbonylmethyl)-4-methylpentanoyl]-L-tryptophane methylamide) intracerebroventricularly (i.c.v., 10 ng/rat). While 10 mg/kg doxycycline significantly increased the SWD number for 1 hour, GM6001 significantly increased the SWD number during the whole four-hour recording period.

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Why is it important?

Our results could indicate that the induction of MMPs in the epileptic brain, besides contributing to structural remodeling, would also be associated with such functions as homeostatic synaptic plasticity which might counteract epileptic seizures.

Perspectives