CCR2 Deficiency Impairs Macrophage Infiltration and Improves Cognitive Function after Traumatic Brain Injury

Autor: Sarah H. Wang, Myrna L. Cozen, Eric J. Huang, Mary C. Nakamura, Jialing Liu, Deborah Bingham, Christine L. Hsieh, Eréne C. Niemi, Israel F. Charo, Jiasheng Zhang, Chih Cheng Lee
Rok vydání: 2014
Předmět:
Male
CCR2
Myeloid
animal diseases
Hippocampus
Open field
Mice
Receptors
Macrophage
chemotaxis
Postural Balance
Mice
Knockout
CD11b Antigen
traumatic brain injury
Brain
hemic and immune systems
Motor coordination
medicine.anatomical_structure
Neurological
Mental health
medicine.symptom
Psychology
behavior studies
Physical Injury - Accidents and Adverse Effects
Receptors
CCR2
Traumatic brain injury
Knockout
Clinical Sciences
Inflammation
macrophage
Traumatic Brain Injury (TBI)
Motor Activity
parasitic diseases
medicine
Animals
Maze Learning
Traumatic Head and Spine Injury
Neurology & Neurosurgery
flow cytometry
Macrophages
Neurosciences
Original Articles
brain injury
medicine.disease
Brain Disorders
nervous system
inflammation
Brain Injuries
Immunology
Neurology (clinical)
Cognition Disorders
Zdroj: Journal of neurotrauma, vol 31, iss 20
ISSN: 1557-9042
0897-7151
Popis: Traumatic brain injury (TBI) provokes inflammatory responses, including a dramatic rise in brain macrophages in the area of injury. The pathway(s) responsible for macrophage infiltration of the traumatically injured brain and the effects of macrophages on functional outcomes are not well understood. C-C-chemokine receptor 2 (CCR2) is known for directing monocytes to inflamed tissues. To assess the role of macrophages and CCR2 in TBI, we determined outcomes in CCR2-deficient (Ccr2(-/-)) mice in a controlled cortical impact model. We quantified brain myeloid cell numbers post-TBI by flow cytometry and found that Ccr2(-/-) mice had greatly reduced macrophage numbers (∼80-90% reduction) early post-TBI, compared with wild-type mice. Motor, locomotor, and cognitive outcomes were assessed. Lack of Ccr2 improved locomotor activity with less hyperactivity in open field testing, but did not affect anxiety levels or motor coordination on the rotarod three weeks after TBI. Importantly, Ccr2(-/-) mice demonstrated greater spatial learning and memory, compared with wild-type mice eight weeks after TBI. Although there was no difference in the volume of tissue loss, Ccr2(-/-) mice had significantly increased neuronal density in the CA1-CA3 regions of the hippocampus after TBI, compared with wild-type mice. These data demonstrate that Ccr2 directs the majority of macrophage homing to the brain early after TBI and indicates that Ccr2 may facilitate harmful responses. Lack of Ccr2 improves functional recovery and neuronal survival. These results suggest that therapeutic blockade of CCR2-dependent responses may improve outcomes following TBI.
Databáze: OpenAIRE
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