Tumor necrosis factor α antagonism improves neurological recovery in murine intracerebral hemorrhage.
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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.
Disease Models, Animal
Mice, Inbred C57BL
Nervous System Diseases
Recovery of Function
Tumor Necrosis Factor-alpha
Published Version (Please cite this version)10.1186/1742-2094-10-103
Publication InfoLei, Beilei; Dawson, Hana N; Roulhac-Wilson, Briana; Wang, Haichen; Laskowitz, Daniel T; & James, Michael L (2013). Tumor necrosis factor α antagonism improves neurological recovery in murine intracerebral hemorrhage. J Neuroinflammation, 10. pp. 103. 10.1186/1742-2094-10-103. Retrieved from https://hdl.handle.net/10161/14240.
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Adjunct Assistant Professor in the Department of Neurology
Our laboratory studies the role of tau protein in neurodegeneration. Aggregated tau protein is a hallmark feature of a group of neurodegenerative dementias called tauopathies. This group of diseases accounts for a large majority of all dementias and includes Alzheimer's disease, Pick's disease and frontotemporal dementia to name a few. To model tauopathies, we overexpressed normal and mutated human tau protein or no tau protein in the central nervous system of transgenic mice. Several of t
Associate Professor of Anesthesiology
I have an extensive background in neuroanesthesia and neurointensive care and a special research interest in translational and clinical research aspects of intracerebral hemorrhage. After completing residencies in neurology and anesthesiology with fellowships in neurocritical care, neuroanesthesia, and vascular neurology, I developed a murine model of intracerebral hemorrhage in the Multidisciplinary Neuroprotection Laboratories at Duke University. After optimization of the model, I h
Professor of Neurology
Our laboratory uses molecular biology, cell culture, and animal modeling techniques to examine the CNS response to acute injury. In particular, our laboratory examines the role of microglial activation and the endogenous CNS inflammatory response in exacerbating secondary injury following acute brain insult. Much of the in vitro work in this laboratory is dedicated to elucidating cellular responses to injury with the ultimate goal of exploring new therapeutic interventions in the clinical settin
Assistant Professor of Neurology
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