Cerebral Ischemic Stroke: Cellular Fate and Therapeutic Opportunities

Front Biosci (Landmark Ed). 2019 Jan 1;24:435-450.


In cerebral tissues, due to continuous and high metabolic demand, energy is produced exclusively by mitochondrial oxidative phosphorylation (OXPHOS). Obstruction of blood flow leads to cerebral ischemia, hypoxia and decreased cellular ATP production. The reactive oxygen species (ROS) generated as by-product of OXPHOS alter many intracellular signaling pathways and result in damaged cellular components. Under such hypoxic conditions, a key factor known as hypoxia inducible factor 1 (HIF1) is stabilized and activated and such activation induces expression of a defined set of target genes which are required for cell survival and angiogenesis. Reperfusion that follows such ischemia alters signaling pathways which are involved in cellular fate. Here, we will review the role of ROS, HIF-1 alpha and other signaling network in mitochondrial dysfunction and cell fate determination in ischemia-reperfusion models in the brain. We will also address both current and future therapeutic strategies for clinical significance that are being developed for treatment of cerebral ischemia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain Ischemia / drug therapy
  • Brain Ischemia / metabolism*
  • Brain Ischemia / physiopathology
  • Free Radical Scavengers / therapeutic use
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Mitochondria / metabolism
  • Platelet Aggregation Inhibitors / therapeutic use
  • Reactive Oxygen Species / metabolism*
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / physiopathology
  • Stroke / drug therapy
  • Stroke / metabolism*
  • Stroke / physiopathology


  • Free Radical Scavengers
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Platelet Aggregation Inhibitors
  • Reactive Oxygen Species