Ethyl pyruvate alleviates early brain injury following subarachnoid hemorrhage in rats

Acta Neurochir (Wien). 2016 Jun;158(6):1069-76. doi: 10.1007/s00701-016-2795-3. Epub 2016 Apr 12.


Background: Previous studies have demonstrated the neuroprotective effects of ethyl pyruvate in central nervous system (CNS) diseases. However, whether ethyl pyruvate attenuates early brain injury after subarachnoid hemorrhage (SAH) remains unknown. This study was conducted to investigate the potential effects of ethyl pyruvate on early brain injury induced by SAH and explore the underlying mechanisms.

Methods: Eighty-eight male Sprague-Dawley rats were used. An SAH model was induced by endovascular perforation. Ethyl pyruvate (100 mg/kg) or a vehicle was administered intraperitoneally at 1 h after SAH induction. SAH grade, neurological scores, brain water content, Evans blue extravasation, Western blots, and immunofluorescence were used to study the mechanisms of ethyl pyruvate.

Results: Ethyl pyruvate treatment inhibited microglia activation and reduced the expression of proinflammatory cytokines (IL-1β and TNF-α). Ethyl pyruvate treatment also prevented disruption of tight junction proteins (occluding and claudin-5) and reduced expression of MMP-9. In addition, ethyl pyruvate treatment markedly reduced TUNEL-positive cells and expression of cleaved caspase-3.

Conclusions: Our results indicated that ethyl pyruvate treatment attenuated early brain injury and improved neurological function after SAH by inhibiting microglia activation and apoptosis and stabilizing the BBB.

Keywords: Apoptosis; Blood brain barrier; Early brain injury; Ethyl pyruvate; Subarachnoid hemorrhage.

MeSH terms

  • Animals
  • Apoptosis
  • Blood-Brain Barrier / drug effects
  • Brain Injuries / drug therapy*
  • Brain Injuries / etiology
  • Claudin-5 / metabolism
  • Cytokines / metabolism
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Neuroprotective Agents / metabolism
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Pyruvates / pharmacology
  • Pyruvates / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Subarachnoid Hemorrhage / complications
  • Subarachnoid Hemorrhage / drug therapy*
  • Subarachnoid Hemorrhage / metabolism


  • Claudin-5
  • Cytokines
  • Neuroprotective Agents
  • Pyruvates
  • ethyl pyruvate
  • Matrix Metalloproteinase 9