Minocycline attenuates microglia activation and blocks the long-term epileptogenic effects of early-life seizures

Neurobiol Dis. 2012 May;46(2):425-30. doi: 10.1016/j.nbd.2012.02.006. Epub 2012 Feb 16.


Innate immunity mediated by microglia appears to play a crucial role in initiating and propagating seizure-induced inflammatory responses. To address the role of activated microglia in the pathogenesis of childhood epilepsy, we first examined the time course of microglia activation following kainic acid-induced status epilepticus (KA-SE) in Cx3cr1(GFP/+) transgenic mice whose microglia are fluorescently labeled. We then determined whether this seizure-induced microglia activation primes the central immune response to overreact and to increase the susceptibility to a second seizure later in life. We used an inhibitor of microglia activation, minocycline, to block the seizure-induced inflammation to determine whether innate immunity plays a causal role in mediating the long-term epileptogenic effects of early-life seizure. First status epilepticus was induced at postnatal day (P) 25 and a second status at P39. KA-SE at P25 caused nearly a two-fold increase in microglia activation within 24h. Significant seizure-induced activation persisted for 7 days and returned to baseline by 14 days. P39 animals with prior exposure to KA-SE not only responded with greater microglial activation in response to "second hit" of KA, but shorter latency to express seizures. Inhibition of seizure-induced inflammation by 7 day minocycline post-treatment abrogated both the exaggerated microglia activation and the increased susceptibility to the second seizure later in life. The priming effect of early-life seizures is accompanied by modified and rapidly reactivated microglia. Our results suggest that anti-inflammatory therapy after SE may be useful to block the epileptogenic process and mitigate the long-term damaging effects of early-life seizures.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Mice
  • Mice, Transgenic
  • Microglia / drug effects*
  • Microglia / metabolism*
  • Minocycline / pharmacology
  • Minocycline / therapeutic use*
  • Neural Inhibition / drug effects*
  • Neural Inhibition / physiology
  • Seizures / physiopathology*
  • Seizures / prevention & control*
  • Time Factors


  • Minocycline