The role of the sonic hedgehog signaling pathway in early brain injury after experimental subarachnoid hemorrhage in rats

Neurosci Lett. 2013 Sep 27:552:81-6. doi: 10.1016/j.neulet.2013.07.042. Epub 2013 Aug 7.

Abstract

Previous studies have demonstrated that the sonic hedgehog (Shh) pathway plays a neuro-protective role. However, whether the Shh pathway is induced by subarachnoid hemorrhage (SAH) has not been investigated. We sought to investigate Shh activation in the cortex in the early stage of SAH, and assessed the effect of cyclopamine (a specific inhibitor of the Shh pathway) on Shh pathway regulation and evaluated the impact of cyclopamine on SAH. We found that the Shh pathway was up-regulated in the cortex after SAH, and that blocking the Shh pathway increased cell apoptosis. Early brain damages, including brain edema, blood-brain barrier impairment, and cortical apoptosis were significantly aggravated following with cyclopamine treatment compared with vehicle treatment. Our results suggest that the Shh pathway should be activated in the brain after SAH, and plays a beneficial role in SAH development, possibly by inhibiting cerebral oxidative stress through induction of antioxidant and detoxifying enzymes.

Keywords: Cyclopamine; Early brain injury; Sonic hedgehog pathway; Subarachnoid hemorrhage.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Blood-Brain Barrier / drug effects
  • Brain Edema / complications
  • Brain Edema / metabolism
  • Brain Edema / pathology
  • Brain Injuries / complications
  • Brain Injuries / metabolism*
  • Brain Injuries / pathology
  • Cerebral Cortex / injuries
  • Cerebral Cortex / metabolism*
  • Hedgehog Proteins / metabolism*
  • Male
  • Rats
  • Signal Transduction / drug effects
  • Subarachnoid Hemorrhage / complications
  • Subarachnoid Hemorrhage / metabolism*
  • Subarachnoid Hemorrhage / pathology
  • Up-Regulation / drug effects
  • Veratrum Alkaloids / pharmacology

Substances

  • Hedgehog Proteins
  • Shh protein, rat
  • Veratrum Alkaloids
  • cyclopamine