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: Beilei Lei, Hana N Dawson, Briana Roulhac-Wilson, Haichen Wang, Daniel T Laskowitz, Michael L James
• Journal: Journal of neuroinflammation (J Neuroinflammation) Vol. 10 Pg. 103 (Aug 20 2013) ISSN: 1742-2094 [Electronic] England
• PMID: 23962089 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Antibodies, Monoclonal (therapeutic use)
• Cerebral Hemorrhage (immunology, pathology, therapy)
• Disease Models, Animal
• Inflammation (immunology, metabolism, therapy)
• Male
• Mice
• Mice, Inbred C57BL
• Nervous System Diseases (immunology, pathology, therapy)
• Random Allocation
• Recovery of Function (immunology)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, physiology)