Transient neuroprotection by minocycline following traumatic brain injury is associated with attenuated microglial activation but no changes in cell apoptosis or neutrophil infiltration

Nicole Bye, Mark Habgood, Jennifer Kay Callaway, N Malakooti, Ann Potter, Thomas K Kossmann, Maria Cristina Morganti-Kossmann

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208 Citations (Scopus)


Cerebral inflammation and apoptotic cell death are two processes implicated in the progressive tissue damage that occurs following traumatic brain injury (TBI), and strategies to inhibit one or both of these pathways are being investigated as potential therapies for TBI patients. The tetracycline derivative minocycline was therapeutically effective in various models of central nervous system injury and disease, via mechanisms involving suppression of inflammation and apoptosis. We therefore investigated the effect of minocycline in TBI using a closed head injury model. Following TBI, mice were treated with minocycline or vehicle, and the effect on neurological outcome, lesion volume, inflammation and apoptosis was evaluated for up to 7 days. Our results show that while minocycline decreases lesion volume and improves neurological outcome at I day post-trauma, this response is not maintained at 4 days. The early beneficial effect is likely not due to anti-apoptotic mechanisms, as the density of apoptotic cells is not affected at either time-point. However, protection by minocycline is associated with a selective anti-inflammatory response, in that microglial activation and interleukin-1 beta expression are reduced, while neutrophil infiltration and expression of multiple cytokines are not affected. These findings demonstrate that further studies on minocycline in TBI are necessary in order to consider it as a novel therapy for brain-injured patients. Crown Copyright (c) 2006 Published by Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)220 - 233
Number of pages13
JournalExperimental Neurology
Issue numberDec 2006
Publication statusPublished - 2007

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