Intranasal surfactant protein D as neuroprotective rescue in a neonatal rat model of periventricular leukomalacia

J Matern Fetal Neonatal Med. 2017 Feb;30(4):446-451. doi: 10.1080/14767058.2016.1174996. Epub 2016 May 16.

Abstract

Background: Periventricular leukomalacia (PVL) is the leading cause of neurocognitive deficits in children with prematurity. We previously hypothesized that surfactant protein D (SPD) with its ability to bind toll-like receptors may have a possible ameliorating effect in PVL.

Methods: Three groups were defined as: LPS-administered and postnatal intranasal saline administered group, LPS-administered and postnatal intranasal SPD-treated group, and control group. Twenty-eight offspring rats were reared with their dams until their sacrifice for histological evaluation on day 7.

Results: A significant loss of brain weight occurred in the LPS group compared with controls. The postnatal intranasal SPD treatment significantly reduced the number of TUNEL-positive cells in the periventricular white matter as compared with the LPS-treated group. Compared with the control group, LPS injection in the rat brain significantly reduced the MBP-positive staining. Postnatal SPD treatment greatly prevented LPS-stimulated loss of MBP staining.

Conclusions: Present study demonstrated a neuroprotective effect of SPD in a rat model of PVL. Our results offer future implications towards increasing our understanding about multifactorial mechanisms underlying periventricular leukomalacia and developing plausible therapeutic strategies in order to prevent neurocognitive deficits in preterm infants.

Keywords: Nasal drug delivery; newborn; periventricular leukomalacia; surfactant protein D.

MeSH terms

  • Administration, Intranasal
  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects*
  • Brain / drug effects*
  • Brain / growth & development
  • Brain / pathology
  • Disease Models, Animal
  • Female
  • Leukomalacia, Periventricular / drug therapy*
  • Leukomalacia, Periventricular / pathology
  • Neuroprotective Agents / metabolism
  • Neuroprotective Agents / therapeutic use*
  • Pregnancy
  • Pulmonary Surfactant-Associated Protein D / therapeutic use*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Single-Blind Method
  • Statistics, Nonparametric

Substances

  • Neuroprotective Agents
  • Pulmonary Surfactant-Associated Protein D