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

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Lei, B; Dawson, HN; Roulhac-Wilson, B; Wang, H; Laskowitz, DT; James, ML

Published Date

  • August 20, 2013

Published In

Volume / Issue

  • 10 /

Start / End Page

  • 103 -

PubMed ID

  • 23962089

Pubmed Central ID

  • 23962089

Electronic International Standard Serial Number (EISSN)

  • 1742-2094

Digital Object Identifier (DOI)

  • 10.1186/1742-2094-10-103

Language

  • eng

Conference Location

  • England