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National Institute of Environmental Health Sciences

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Publication Detail

Title: Comparison of the effect of minocycline and simvastatin on functional recovery and gene expression in a rat traumatic brain injury model.

Authors: Vonder Haar, Cole; Anderson, Gail D; Elmore, Brandy E; Moore, Lynn H; Wright, Amanda M; Kantor, Eric D; Farin, Fred M; Bammler, Theo K; MacDonald, James W; Hoane, Michael R

Published In J Neurotrauma, (2014 May 15)

Abstract: The goal of this study was to compare the effects of minocycline and simvastatin on functional recovery and brain gene expression after a cortical contusion impact (CCI) injury. Dosage regimens were designed to provide serum concentrations in a rat model in the range obtained with clinically approved doses; minocycline 60 mg/kg q12h and simvastatin 10 mg/kg q12h for 72 h. Functional recovery was assessed using motor and spatial learning tasks and neuropathological measurements. Microarray-based transcriptional profiling was used to determine the effect on gene expression at 24 h, 72 h, and 7 days post-CCI. Gene Ontology analysis (GOA) was used to evaluate the effect on relevant biological pathways. Both minocycline and simvastatin improved fine motor function, but not gross motor or cognitive function. Minocycline modestly decreased lesion size with no effect of simvastatin. At 24 h post-CCI, GOA identified a significant effect of minocycline on chemotaxis, blood circulation, immune response, and cell to cell signaling pathways. Inflammatory pathways were affected by minocycline only at the 72 h time point. There was a minimal effect of simvastatin on gene expression 24 h after injury, with increasing effects at 72 h and 7 days. GOA identified a significant effect of simvastatin on inflammatory response at 72 h and 7 days. In conclusion, treatment with minocycline and simvastatin resulted in significant effects on gene expression in the brain reflecting adequate brain penetration without producing significant neurorestorative effects.

PubMed ID: 24308531 Exiting the NIEHS site

MeSH Terms: Animals; Brain Injuries/complications; Brain Injuries/genetics; Brain Injuries/pathology; Disease Models, Animal; Male; Minocycline/pharmacokinetics; Minocycline/pharmacology*; Neuroprotective Agents/pharmacokinetics; Neuroprotective Agents/pharmacology*; Oligonucleotide Array Sequence Analysis; Rats; Rats, Sprague-Dawley; Recovery of Function/drug effects*; Simvastatin/pharmacokinetics; Simvastatin/pharmacology*; Transcriptome/drug effects*

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