title: Minocycline fails to exert antiepileptogenic effects in a rat status epilepticus model.
abstract: The tetracycline antibiotic minocycline can exert strong anti-inflammatory, antioxidant, and antiapoptotic effects. There is cumulating evidence that epileptogenic brain insults trigger neuroinflammation and anti-inflammatory concepts can modulate the process of epileptogenesis. Based on the mechanisms of action discussed for minocycline, the compound is of interest for intervention studies as it can prevent the polarization of microglia into a pro-inflammatory state. Here, we assessed the efficacy of sub-chronic minocycline administration initiated immediately following an electrically-induced status epilepticus in rats. The treatment did not affect the development of spontaneous seizures. However, minocycline attenuated behavioral long-term consequences of status epilepticus with a reduction in hyperactivity and hyperlocomotion. Furthermore, the compound limited the spatial learning deficits observed in the post-status epilepticus model. The typical status epilepticus-induced neuronal cell loss was evident in the hippocampus and the piriform cortex. Minocycline exposure selectively protected neurons in the piriform cortex and the hilus, but not in the hippocampal pyramidal layer. In conclusion, the data argue against an antiepileptogenic effect of minocycline in adult rats. However, the findings suggest a disease-modifying impact of the tetracycline affecting the development of behavioral co-morbidities, as well as long-term consequences on spatial learning. In addition, minocycline administration resulted in a selective neuroprotective effect. Although strong anti-inflammatory effects have been proposed for minocycline, we could not verify these effects in our experimental model. Considering the multitude of mechanisms claimed to contribute to minocycline's effects, it is of interest to further explore the exact mechanisms underlying the beneficial effects in future studies.
authors.affiliation: Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig-Maximilians-University (LMU), Koeniginstr. 16, D-80539 Munich, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Russmann
authors.affiliation: Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig-Maximilians-University (LMU), Koeniginstr. 16, D-80539 Munich, Germany.
authors.forename: Joanna
authors.initials: J
authors.lastname: Goc
authors.affiliation: Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig-Maximilians-University (LMU), Koeniginstr. 16, D-80539 Munich, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Boes
authors.affiliation: Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig-Maximilians-University (LMU), Koeniginstr. 16, D-80539 Munich, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Ongerth
authors.affiliation: Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig-Maximilians-University (LMU), Koeniginstr. 16, D-80539 Munich, Germany.
authors.forename: Josephine D
authors.initials: JD
authors.lastname: Salvamoser
authors.affiliation: Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig-Maximilians-University (LMU), Koeniginstr. 16, D-80539 Munich, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Siegl
authors.affiliation: Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig-Maximilians-University (LMU), Koeniginstr. 16, D-80539 Munich, Germany. Electronic address: potschka@pharmtox.vetmed.uni-muenchen.de.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Potschka
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D002540:Cerebral Cortex / Q000473:pathology; D004558:Electric Stimulation; D005260:Female; D006624:Hippocampus / Q000473:pathology; D018782:Maze Learning / Q000187:drug effects; D017628:Microglia / Q000187:drug effects; D008911:Minocycline / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000188:drug therapy; D013226:Status Epilepticus / Q000188:drug therapy*
chemical_list: D000927:Anticonvulsants; D018696:Neuroprotective Agents; D008911:Minocycline
keywords: Epileptogenesis; Learning; Microglia; Minocycline; Neuroinflammation; Status epilepticus