Neuroprotective Effects of Bioactive Compounds and MAPK Pathway Modulation in Ischemia-Stressed PC12 Pheochromocytoma Cells

This review surveys the efforts taken to investigate in vitro neuroprotective features of synthetic compounds and cell-released growth factors on PC12 clonal cell line temporarily deprived of oxygen and glucose followed by reoxygenation (OGD/R). These cells have been used previously to mimic some of the properties of in vivo brain ischemia-reperfusion-injury (IRI) and have been instrumental in identifying common mechanisms such as calcium overload, redox potential, lipid peroxidation and MAPKs modulation. In addition, they were useful for establishing the role of certain membrane penetrable cocktails of antioxidants as well as potential growth factors which may act in neuroprotection. Pharmacological mechanisms of neuroprotection addressing modulation of the MAPK cascade and increased redox potential by natural products, drugs and growth factors secreted by stem cells, in either undifferentiated or nerve growth factor-differentiated PC12 cells exposed to ischemic conditions are discussed for future prospects in neuroprotection studies.