Tumor necrosis factor α antagonism improves neurological recovery in murine intracerebral hemorrhage.

Lei, Beilei

Dawson, Hana N

Roulhac-Wilson, Briana

Wang, Haichen

Laskowitz, Daniel T

James, Michael L

England

2017-05-01T17:21:10Z

2017-05-01T17:21:10Z

2013-08-20

BACKGROUND: Intracerebral hemorrhage (ICH) is a devastating stroke subtype characterized by a prominent neuroinflammatory response. Antagonism of pro-inflammatory cytokines by specific antibodies represents a compelling therapeutic strategy to improve neurological outcome in patients after ICH. To test this hypothesis, the tumor necrosis factor alpha (TNF-α) antibody CNTO5048 was administered to mice after ICH induction, and histological and functional endpoints were assessed. METHODS: Using 10 to 12-week-old C57BL/6J male mice, ICH was induced by collagenase injection into the left basal ganglia. Brain TNF-α concentration, microglia activation/macrophage recruitment, hematoma volume, cerebral edema, and rotorod latency were assessed in mice treated with the TNF-α antibody, CNTO5048, or vehicle. RESULTS: After ICH induction, mice treated with CNTO5048 demonstrated reduction in microglial activation/macrophage recruitment compared to vehicle-treated animals, as assessed by unbiased stereology (P = 0.049). This reduction in F4/80-positive cells was associated with a reduction in cleaved caspase-3 (P = 0.046) and cerebral edema (P = 0.026) despite similar hematoma volumes, when compared to mice treated with vehicle control. Treatment with CNTO5048 after ICH induction was associated with a reduction in functional deficit when compared to mice treated with vehicle control, as assessed by rotorod latencies (P = 0.024). CONCLUSIONS: Post-injury treatment with the TNF-α antibody CNTO5048 results in less neuroinflammation and improved functional outcomes in a murine model of ICH.

https://www.ncbi.nlm.nih.gov/pubmed/23962089

1742-2094-10-103

1742-2094

https://hdl.handle.net/10161/14240

eng

Springer Science and Business Media LLC

J Neuroinflammation

10.1186/1742-2094-10-103

Animals

Antibodies, Monoclonal

Cerebral Hemorrhage

Disease Models, Animal

Inflammation

Male

Mice

Mice, Inbred C57BL

Nervous System Diseases

Random Allocation

Recovery of Function

Tumor Necrosis Factor-alpha

Tumor necrosis factor α antagonism improves neurological recovery in murine intracerebral hemorrhage.

Journal article

Laskowitz, Daniel T|0000-0003-3430-8815

James, Michael L|0000-0002-8715-5210

https://www.ncbi.nlm.nih.gov/pubmed/23962089

103

Anesthesiology

Anesthesiology, Neuroanesthesia

Basic Science Departments

Clinical Science Departments

Duke

Duke Clinical Research Institute

Institutes and Centers

Neurobiology

Neurology

Neurology, Neurocritical Care

Neurosurgery

School of Medicine

Published online

10