Brain Natriuretic Peptide Improves Long-Term Functional Recovery after Acute CNS Injury in Mice
Abstract
There is emerging evidence to suggest that brain natriuretic peptide (BNP) is elevated
after acute brain injury, and that it may play an adaptive role in recovery through
augmentation of cerebral blood flow (CBF). Through a series of experiments, we tested
the hypothesis that the administration of BNP after different acute mechanisms of
central nervous system (CNS) injury could improve functional recovery by improving
CBF. C57 wild-type mice were exposed to either pneumatic-induced closed traumatic
brain injury (TBI) or collagenase-induced intracerebral hemorrhage (ICH). After injury,
either nesiritide (hBNP) (8 μg/kg) or normal saline were administered via tail vein
injection at 30 min and 4 h. The mice then underwent functional neurological testing
via rotorod latency over the following 5 days and neurocognitive testing via Morris
water maze testing on days 24–28. Cerebral blood flow (CBF) was assessed by laser
Doppler from 25 to 90 min after injury. After ICH, mRNA polymerase chain reaction
(PCR) and histochemical staining were performed during the acute injury phase (<24 h)
to determine the effects on inflammation. Following TBI and ICH, administration of
hBNP was associated with improved functional performance as assessed by rotorod and
Morris water maze latencies (p < 0.01). CBF was increased (p < 0.05), and inflammatory
markers (TNF-α and IL-6; p < 0.05), activated microglial (F4/80; p < 0.05), and neuronal
degeneration (Fluoro-Jade B; p < 0.05) were reduced in mice receiving hBNP. hBNP improves
neurological function in murine models of TBI and ICH, and was associated with enhanced
CBF and downregulation of neuroinflammatory responses. hBNP may represent a novel
therapeutic strategy after acute CNS injury.
Type
Journal articleSubject
brain natriuretic peptidecerebral blood flow
intracerebral hemorrhage
nesiritide
neuroinflammation
neuroprotection
traumatic brain injury
cerebral-blood-flow
congestive-heart-failure
acute ischemic-stroke
nitric-oxide synthase
hypertensive-rats
angiotensin-ii
plasma-concentrations
optical fractionator
l-arginine
critical care medicine
clinical neurology
neurosciences
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https://hdl.handle.net/10161/5971Published Version (Please cite this version)
10.1089/neu.2009.1022Citation
Michael L. James, Haichen Wang, Talaignair Venkatraman, Pingping Song, Christopher
D. Lascola, and Daniel T. Laskowitz. Journal of Neurotrauma. January 2010, 27(1):
217-228
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Show full item recordScholars@Duke
Michael Lucas James
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
Christopher David Lascola
Associate Professor of Radiology
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
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