RT Journal Article
SR Electronic
T1 Interfering with the Chronic Immune Response Rescues Chronic Degeneration After Traumatic Brain Injury
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9962
OP 9975
DO 10.1523/JNEUROSCI.1898-15.2016
VO 36
IS 38
A1 Ali Ertürk
A1 Susanne Mentz
A1 Erik E. Stout
A1 Maj Hedehus
A1 Sara L. Dominguez
A1 Lisa Neumaier
A1 Franziska Krammer
A1 Gemma Llovera
A1 Karpagam Srinivasan
A1 David V. Hansen
A1 Arthur Liesz
A1 Kimberly A. Scearce-Levie
A1 Morgan Sheng
YR 2016
UL http://www.jneurosci.org/content/36/38/9962.abstract
AB After 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 STATEMENT Traumatic 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.