Interfering with the Chronic Immune Response Rescues Chronic Degeneration After Traumatic Brain Injury

Ertürk, Ali; Mentz, Susanne; Stout, Erik E.; Hedehus, Maj; Dominguez, Sara L.; Neumaier, Lisa; Krammer, Franziska; Llovera, Gemma; Srinivasan, Karpagam; Hansen, David V.; Liesz, Arthur; Scearce-Levie, Kimberly A. und Sheng, Morgan (2016): Interfering with the Chronic Immune Response Rescues Chronic Degeneration After Traumatic Brain Injury. In: Journal of Neuroscience, Bd. 36, Nr. 38: S. 9962-9975

Abstract

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 CX(3)CR1, 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Fakultätsübergreifende Einrichtungen: Center for International Health (CIH)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0270-6474
• Sprache: Englisch