natriuretic-peptide--c-type and Brain-Injuries

C-type natriuretic peptide (CNP) is an important vascular regulator that is present in the brain. Our previous study demonstrated the innate neuroprotectant role of CNP in the neonatal brain after hypoxic-ischemic (HI) insults. In this study, we further explored the role of CNP in cerebrovascular pathology using both in vivo and in vitro models. In a neonatal mouse HI brain injury model, we found that intracerebroventricular administration of recombinant CNP dose-dependently reduces brain infarct size. CNP significantly decreases brain edema and immunoglobulin G (IgG) extravasation into the brain tissue, suggesting a vasculoprotective effect of CNP. Moreover, in primary brain microvascular endothelial cells (BMECs), CNP dose-dependently protects BMEC survival and monolayer integrity against oxygen-glucose deprivation (OGD). The vasculoprotective effect of CNP is mediated by its innate receptors NPR2 and NPR3, in that inhibition of either NPR2 or NPR3 counteracts the protective effect of CNP on IgG leakage after HI insult and BMEC survival under OGD. Of importance, CNP significantly ameliorates brain atrophy and improves neurological deficits after HI insults. Altogether, the present study indicates that recombinant CNP exerts vascular protection in neonatal HI brain injury via its innate receptors, suggesting a potential therapeutic target for the treatment of neonatal HI brain injury.

Topics: Animals; Animals, Newborn; Brain; Brain Edema; Brain Infarction; Brain Injuries; Cells, Cultured; Endothelial Cells; Female; Hypoxia-Ischemia, Brain; Infusions, Intraventricular; Male; Mice; Natriuretic Peptide, C-Type; Neuroprotective Agents; Vascular System Injuries

C-type natriuretic peptide (CNP), a member of the natriuretic peptide family, is produced in vascular endothelium. We assessed the accuracy of natriuretic (NT)-proCNP, the N-terminal fragment of the C-type natriuretic peptide precursor, in predicting development of sepsis in multiple-traumatized patients with/without traumatic brain injury verified by computed tomography.. Retrospective clinical study.. Level II trauma center.. Three patient groups were stratified according to computed tomography results: isolated traumatic brain injury (n = 20), multiple-traumatized with traumatic brain injury (n = 26) and multiple-traumatized without traumatic brain injury (n = 26). During 13 days after multiple trauma, 37 (51%) patients developed sepsis.. Circulating plasma NT-proCNP levels were measured daily (days 0-13) in all patients. Without any retrospective stratification of trauma patients, plasma NT-proNCP levels did not differ in septic (n = 37) and nonseptic (n = 35) patients (p = .505). Between days 2 and 6 posttrauma, there was a significant (p = .002) increase of circulating NT-proCNP in multiple-traumatized patients without traumatic brain injury who developed sepsis (n = 19) compared with nonseptic multiple-traumatized patients without traumatic brain injury. Conversely, in septic patients either with traumatic brain injury alone or with multiple trauma and traumatic brain injury, the NT-proCNP showed a trend toward lower levels than in nonseptic patients. Prediction of sepsis (receiver-operating characteristic test) from days 2 to 6 after multiple trauma by NT-proCNP in patients without traumatic brain injury was accurate with an area under the curve of 0.84 +/- 0.03. The optimal cutoff value of 2.3 pmol/L produced sensitivity of 84% to 96% and specificity of 61% to 91% from day 2 to 6 after trauma.. Our data showed that the levels of circulating NT-proCNP between multiple-traumatized patients without traumatic brain injury who do and do not develop sepsis are distinctly different. Plasma NT-proCNP concentration can potentially serve as an accurate predictor of sepsis in this cohort of patients.

Topics: Adult; Analysis of Variance; APACHE; Austria; Biomarkers; Brain Injuries; Cohort Studies; Critical Care; Female; Follow-Up Studies; Glasgow Coma Scale; Hospital Mortality; Humans; Injury Severity Score; Male; Middle Aged; Multiple Trauma; Natriuretic Peptide, C-Type; Normal Distribution; Predictive Value of Tests; Probability; Retrospective Studies; Risk Assessment; Sepsis; Survival Rate; Trauma Centers; Young Adult

Topics: Biomarkers; Brain Injuries; Critical Care; Critical Illness; Female; Humans; Intensive Care Units; Male; Multiple Trauma; Natriuretic Peptide, C-Type; Predictive Value of Tests; Prognosis; Risk Assessment; Sepsis; Survival Analysis

Topics: Animals; Brain Injuries; Endotoxins; Female; Male; Natriuretic Peptide, C-Type; Neurotensin; Rabbits