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Tumor necrosis factor α antagonism improves neurological recovery in murine intracerebral hemorrhage.
- Source :
-
Journal of neuroinflammation [J Neuroinflammation] 2013 Aug 20; Vol. 10, pp. 103. Date of Electronic Publication: 2013 Aug 20. - Publication Year :
- 2013
-
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.<br />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.<br />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).<br />Conclusions: Post-injury treatment with the TNF-α antibody CNTO5048 results in less neuroinflammation and improved functional outcomes in a murine model of ICH.
- Subjects :
- Animals
Cerebral Hemorrhage immunology
Cerebral Hemorrhage pathology
Disease Models, Animal
Inflammation immunology
Inflammation metabolism
Inflammation therapy
Male
Mice
Mice, Inbred C57BL
Nervous System Diseases immunology
Nervous System Diseases pathology
Nervous System Diseases therapy
Random Allocation
Antibodies, Monoclonal therapeutic use
Cerebral Hemorrhage therapy
Recovery of Function immunology
Tumor Necrosis Factor-alpha antagonists & inhibitors
Tumor Necrosis Factor-alpha physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1742-2094
- Volume :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of neuroinflammation
- Publication Type :
- Academic Journal
- Accession number :
- 23962089
- Full Text :
- https://doi.org/10.1186/1742-2094-10-103