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Interfering with the Chronic Immune Response Rescues Chronic Degeneration After Traumatic Brain Injury.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2016 Sep 21; Vol. 36 (38), pp. 9962-75. - Publication Year :
- 2016
-
Abstract
- Unlabelled: 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.<br />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.<br /> (Copyright © 2016 the authors 0270-6474/16/369962-14$15.00/0.)
- Subjects :
- Animals
Brain pathology
CX3C Chemokine Receptor 1
Calcium-Binding Proteins metabolism
Chronic Disease
Dendritic Spines immunology
Dendritic Spines pathology
Dendritic Spines ultrastructure
Disease Models, Animal
Exploratory Behavior physiology
Female
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microfilament Proteins metabolism
Motor Activity
Neurons metabolism
Neurons pathology
Psychomotor Performance physiology
Receptors, Chemokine genetics
Receptors, Chemokine metabolism
Time Factors
Brain Injuries, Traumatic complications
Inflammation etiology
Nerve Degeneration diagnostic imaging
Nerve Degeneration etiology
Nerve Degeneration pathology
Recovery of Function physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 36
- Issue :
- 38
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 27656033
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.1898-15.2016