• Ali Ertürk, Susanne Mentz, Erik E Stout, Maj Hedehus, Sara L Dominguez, Lisa Neumaier, Franziska Krammer, Gemma Llovera, Karpagam Srinivasan, David V Hansen, Arthur Liesz, Kimberly A Scearce-Levie, and Morgan Sheng.
• Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich, 81377 Munich, Germany, Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany, Graduate School of Neuroscience Munich, 82152 Planegg-Martinsried, Germany, and Department of Neuroscience, Genentech, Inc., South San Francisco, California 94080 Ali.Ertuerk@med.uni-muenchen.de.
• J. Neurosci. 2016 Sep 21; 36 (38): 9962-75.

UnlabelledAfter traumatic brain injury (TBI), neurons surviving the initial insult can undergo chronic (secondary) degeneration via poorly understood mechanisms, resulting in long-term cognitive impairment. Although a neuroinflammatory response is promptly activated after TBI, it is unknown whether it has a significant role in chronic phases of TBI (>1 year after injury). Using a closed-head injury model of TBI in mice, we showed by MRI scans that TBI caused substantial degeneration at the lesion site within a few weeks and these did not expand significantly thereafter. However, chronic alterations in neurons were observed, with reduced dendritic spine density lasting >1 year after injury. In parallel, we found a long-lasting inflammatory response throughout the entire brain. Deletion of one allele of CX3CR1, a chemokine receptor, limited infiltration of peripheral immune cells and largely prevented the chronic degeneration of the injured brain and provided a better functional recovery in female, but not male, mice. Therefore, targeting persistent neuroinflammation presents a new therapeutic option to reduce chronic neurodegeneration.Significance StatementTraumatic brain injury (TBI) often causes chronic neurological problems including epilepsy, neuropsychiatric disorders, and dementia through unknown mechanisms. Our study demonstrates that inflammatory cells invading the brain lead to secondary brain damage. Sex-specific amelioration of chronic neuroinflammation rescues the brain degeneration and results in improved motor functions. Therefore, this study pinpoints an effective therapeutic approach to preventing secondary complications after TBI.Copyright © 2016 the authors 0270-6474/16/369962-14$15.00/0.

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