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.
Type
Journal articleSubject
AnimalsAntibodies, Monoclonal
Cerebral Hemorrhage
Disease Models, Animal
Inflammation
Male
Mice
Mice, Inbred C57BL
Nervous System Diseases
Random Allocation
Recovery of Function
Tumor Necrosis Factor-alpha
Permalink
https://hdl.handle.net/10161/14240Published Version (Please cite this version)
10.1186/1742-2094-10-103Publication Info
Lei, 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.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
Collections
More Info
Show full item recordScholars@Duke
Hana Nenicka Dawson
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
Michael Lucas James
Professor of Anesthesiology
With a clinical background in neuroanesthesia and neurointensive care, I have a special
interest in translational research in intracerebral hemorrhage and traumatic brain
injury. I am fortunate to be part of a unique team of highly motivated and productive
individuals who allow me to propel ideas from bench to bedside and the ability to
reverse translate ideas from the bedside back to the bench.
Daniel Todd Laskowitz
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
Haichen Wang
Assistant Professor in Neurology
Alphabetical list of authors with Scholars@Duke profiles.

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy
Rights for Collection: Scholarly Articles
Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info