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 mg=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-a 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.

Recombinant human brain natriuretic peptide attenuates LPS-induced cellular injury in human fetal lung fibroblasts via inhibiting MAPK and NF-κB pathway activation

“…However, the effects of rhBNP on HFL-1 cells in terms of inflammation have not yet been described. rhBNP is known to exert its anti-inflammatory activity in various organs (18)(19)(20)(21). Therefore, further investigation of the mechanism by which rhBNP influences LPS-induced human lung fibroblasts has important clinical implications.…”

Heads and Tails of Natriuretic Peptides: Neuroprotective Role of Brain Natriuretic Peptide

“…Experimental evidences have also described the protective effect of NPs in cerebral injury18, 19, 20, 21; however, although the study of NPs (mainly BNP) has been focused as a biomarker of heart failure3, 26 and biomarker of cardioembolic stroke,5, 6, 7, 8, 9, 10 a clinical analysis about the protective effect of BNP in stroke that confirms the beneficial effect of these molecules has not been performed so far.…”

“…In brain, expression of NP receptors have been described in regions such as the cerebral cortex, limbic area, preoptic–hypothalamic regions, cerebellum, or brainstem,1, 15, 16, 17 and there are experimental evidences that show NPs may exert neuroprotective effects in cultured cells and in vivo studies 18, 19, 20, 21…”

Intrastriatal Injection of Autologous Blood or Clostridial Collagenase as Murine Models of Intracerebral Hemorrhage

“…Lists of possible therapies may be generated by high throughput technologies, such as transcriptomic and proteomic work. While these technologies continue to advance our knowledge of potential therapeutic targets, forward and backward translation of promising targets may be best examined through use of clinically relevant preclinical models [19][20][21][22] . Such models are useful because they allow rapid throughput of selected candidates, examination of mechanisms in vivo, inexpensive investigation of dosing, therapeutic window, and other parameters germane to developing clinical trials [23][24][25] .…”