Effects of pigment epithelium-derived factor on traumatic brain injury

Restor Neurol Neurosci. 2015;33(1):81-93. doi: 10.3233/RNN-140417.

Abstract

Purpose: Pigment epithelium-derived factor (PEDF) is a multifunctional protein with antiangiogenic, anti-inflammatory, neurotrophic and neurogenic properties. The effect of PEDF on traumatic brain injury (TBI) has not been explored. In this study, we aimed to show the in vivo effects of PEDF on lesion volume, cell death and cell proliferation after TBI.

Methods: Rats were subjected to controlled cortical impact injury (CCII). PEDF mRNA brain levels were measured by RT-PCR. The lesion volume, cell proliferation, cell death and microglia activation were assessed in the brains of lesioned animals with intraventricular alzet infusion of PEDF or aCSF, and intraperitoneal injections of BrdU.

Results: We detected a significant increase of PEDF mRNA levels after TBI. PEDF intraventricular infusion showed no significant effect on the contusion volume, whereas the number of dead cells, activated microglia, BrdU-positive cells around the lesion were significantly decreased. In contrast, PEDF application increased cell proliferation in the ipsilateral subventricular zone. No effect was found on cell proliferation in the dentate gyrus.

Conclusion: The present work indicates that PEDF acts as a multifunctional agent after TBI influencing cell death, inflammation and cell proliferation.

Keywords: PEDF; SVZ; cell death; microglia; traumatic brain injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Brain Injuries / drug therapy*
  • Bromodeoxyuridine / metabolism
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems
  • Ectodysplasins / metabolism
  • Eye Proteins / genetics
  • Eye Proteins / metabolism
  • Eye Proteins / therapeutic use*
  • In Situ Nick-End Labeling
  • Male
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism
  • Nerve Growth Factors / therapeutic use*
  • Protease Inhibitors / therapeutic use*
  • RNA, Messenger / metabolism
  • Rats
  • Serpins / genetics
  • Serpins / metabolism
  • Serpins / therapeutic use*
  • Time Factors

Substances

  • Ectodysplasins
  • Eye Proteins
  • Nerve Growth Factors
  • Protease Inhibitors
  • RNA, Messenger
  • Serpins
  • pigment epithelium-derived factor
  • Bromodeoxyuridine