9-cis retinoic acid induces neurorepair in stroke brain

Sci Rep. 2017 Jul 3;7(1):4512. doi: 10.1038/s41598-017-04048-2.

Abstract

The purpose of this study was to examine the neurorestorative effect of delayed 9 cis retinoic acid (9cRA) treatment for stroke. Adult male rats received a 90-min right distal middle cerebral artery occlusion (dMCAo). Animals were separated into two groups with similar infarction sizes, based on magnetic resonance imaging on day 2 after dMCAo. 9cRA or vehicle was given via an intranasal route daily starting from day 3. Stroke rats receiving 9cRA post-treatment showed an increase in brain 9cRA levels and greater recovery in motor function. 9cRA enhanced the proliferation of bromodeoxyuridine (+) cells in the subventricular zone (SVZ) and lesioned cortex in the stroke brain. Using subventricular neurosphere and matrigel cultures, we demonstrated that proliferation and migration of SVZ neuroprogenitor cells were enhanced by 9cRA. Our data support a delayed and non-invasive drug therapy for stroke. Intranasal 9cRA can facilitate the functional recovery and endogenous repair in the ischemic brain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alitretinoin / metabolism*
  • Alitretinoin / pharmacology
  • Animals
  • Body Weight
  • Bone Morphogenetic Protein 7 / metabolism
  • Cell Movement
  • Cell Proliferation
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Disease Models, Animal
  • Immunohistochemistry
  • Lateral Ventricles / drug effects
  • Lateral Ventricles / metabolism
  • Magnetic Resonance Imaging / methods
  • Male
  • Motor Activity
  • Rats
  • Stroke / diagnostic imaging
  • Stroke / etiology
  • Stroke / metabolism*
  • Stroke / pathology*

Substances

  • Bmp7 protein, rat
  • Bone Morphogenetic Protein 7
  • Alitretinoin