Brain natriuretic peptide improves long-term functional recovery after acute CNS injury in mice.
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 microg/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-alpha 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.
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA. james040@mc.duke.edu
Michael L
ML
James
Haichen
H
Wang
Talaignair
T
Venkatraman
Pingping
P
Song
Christopher D
CD
Lascola
Daniel T
DT
Laskowitz
D000208:Acute Disease; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D016207:Cytokines / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D005452:Fluoresceins; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D045283:Natriuretic Agents / Q000494:pharmacology / Q000627:therapeutic use; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology* / Q000627:therapeutic use; D009410:Nerve Degeneration / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009930:Organic Chemicals; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D016896:Treatment Outcome
D016207:Cytokines; D005452:Fluoresceins; D045283:Natriuretic Agents; D018696:Neuroprotective Agents; D009930:Organic Chemicals; D012333:RNA, Messenger; C435731:fluoro jade; D020097:Natriuretic Peptide, Brain