Article

NeuroRX

, Volume 1, Issue 1, pp 17-25

Neuronal death/survival signaling pathways in cerebral ischemia

  • Taku SugawaraAffiliated withDepartment of Neurosurgery, Stanford University School of MedicineDepartment of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine
  • , Miki FujimuraAffiliated withDepartment of Neurosurgery, Stanford University School of MedicineDepartment of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine
  • , Nobuo NoshitaAffiliated withDepartment of Neurosurgery, Stanford University School of MedicineDepartment of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine
  • , Gyung Whan KimAffiliated withDepartment of Neurosurgery, Stanford University School of MedicineDepartment of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine
  • , Atsushi SaitoAffiliated withDepartment of Neurosurgery, Stanford University School of MedicineDepartment of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine
  • , Takeshi HayashiAffiliated withDepartment of Neurosurgery, Stanford University School of MedicineDepartment of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine
  • , Purnima NarasimhanAffiliated withDepartment of Neurosurgery, Stanford University School of MedicineDepartment of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine
  • , Carolina M. MaierAffiliated withDepartment of Neurosurgery, Stanford University School of MedicineDepartment of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine
  • , Pak H. ChanAffiliated withDepartment of Neurosurgery, Stanford University School of MedicineDepartment of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of MedicineNeurosurgical Laboratories, Stanford University Email author 

Summary

Cumulative evidence suggests that apoptosis plays a pivotal role in cell deathin vitro after hypoxia. Apoptotic cell death pathways have also been implicated in ischemic cerebral injury inin vivo ischemia models. Experimental ischemia and reperfusion models, such as transient focal/global ischemia in rodents, have been thoroughly studied and the numerous reports suggest the involvement of cell survival/death signaling pathways in the pathogenesis of apoptotic cell death in ischemic lesions. In these models, reoxygenation during reperfusion provides a substrate for numerous enzymatic oxidation reactions. Oxygen radicals damage cellular lipids, proteins and nucleic acids, and initiate cell signaling pathways after cerebral ischemia. Genetic manipulation of intrinsic antioxidants and factors in the signaling pathways has provided substantial understanding of the mechanisms involved in cell death/survival signaling pathways and the role of oxygen radicals in ischemic cerebral injury. Future studies of these pathways may provide novel therapeutic strategies in clinical stroke.

Key Words

Cerebral ischemia apoptosis signaling pathway oxidative stress