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

J Am Heart Assoc. 2017 Dec 4;6(12):e007329. doi: 10.1161/JAHA.117.007329.

Abstract

Background: Besides the relevant role of brain-type natriuretic peptide (BNP) as biomarker of cardioembolic strokes, new experimental evidences suggest that this peptide may mediate neuroprotective effects. In this study, we have evaluated for the first time the clinical association between BNP (by means of proBNP) and good outcome in ischemic stroke patients, and analyzed the effect of blood BNP increase in an ischemic animal model.

Methods and results: A retrospective study with 2 different cohorts (262 patients in cohort I and 610 in cohort II) from the same prospective stroke registry was performed. proBNP concentration was analyzed within the first 12 hours from stroke onset. The primary predictor variable was functional outcome evaluated by modified Rankin Scale at 3 months. For the experimental study, BNP pretreatment was tested in an ischemic animal model subjected to a transient occlusion of the cerebral artery, and the infarct volume and sensorimotor deficit were evaluated for 14 days. Cardioembolic strokes presented a positive correlation between proBNP concentration and modified Rankin Scale at 3 months; however, noncardioembolic strokes presented a negative correlation. In the logistic regression analysis, noncardioembolic strokes with concentrations of proBNP ≥340 pg/mL were associated with a good outcome. In line with these clinical findings, the experimental study revealed that those BNP pretreated animals presented a reduction on infarct volumes at 24 hours and functional recovery at days 7 and 14 compared with the control groups.

Conclusions: These clinical and experimental evidences support the potential role of BNP as a protective factor against cerebral ischemia.

Keywords: brain natriuretic peptide; cardioembolic stroke; neuroprotection; noncardioembolic stroke.

MeSH terms

  • Animals
  • Biomarkers / blood
  • Brain Ischemia / blood*
  • Brain Ischemia / diagnosis
  • Brain Ischemia / physiopathology
  • Brain Ischemia / prevention & control
  • Chi-Square Distribution
  • Disability Evaluation
  • Disease Models, Animal
  • Infarction, Middle Cerebral Artery / blood*
  • Infarction, Middle Cerebral Artery / diagnosis
  • Infarction, Middle Cerebral Artery / physiopathology
  • Infarction, Middle Cerebral Artery / prevention & control
  • Logistic Models
  • Male
  • Motor Activity
  • Natriuretic Peptide, Brain / administration & dosage
  • Natriuretic Peptide, Brain / blood*
  • Natriuretic Peptide, Brain / pharmacokinetics
  • Neuroprotective Agents / administration & dosage
  • Odds Ratio
  • Prognosis
  • Protective Factors
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Registries
  • Retrospective Studies
  • Risk Factors
  • Sensory Thresholds
  • Stroke / blood*
  • Stroke / diagnosis
  • Stroke / physiopathology
  • Stroke / prevention & control
  • Time Factors

Substances

  • Biomarkers
  • Neuroprotective Agents
  • Natriuretic Peptide, Brain