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.
Item Type: | Journal article |
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Faculties: | Medicine |
Research Centers: | Center for International Health (CIH) |
Subjects: | 600 Technology > 610 Medicine and health |
ISSN: | 0270-6474 |
Language: | English |
Item ID: | 46116 |
Date Deposited: | 27. Apr 2018, 08:10 |
Last Modified: | 04. Nov 2020, 13:22 |