title: Tumor necrosis factor α antagonism improves neurological recovery in murine intracerebral hemorrhage.
abstract: 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.
authors: Multidisciplinary Neuroprotection Laboratories, Durham, NC 27710, USA.
authors: Beilei
authors: B
authors: Lei
authors: Hana N
authors: HN
authors: Dawson
authors: Briana
authors: B
authors: Roulhac-Wilson
authors: Haichen
authors: H
authors: Wang
authors: Daniel T
authors: DT
authors: Laskowitz
authors: Michael L
authors: ML
authors: James
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002543:Cerebral Hemorrhage / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009422:Nervous System Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy; D011897:Random Allocation; D020127:Recovery of Function / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha
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