Death effector activation in the subventricular zone subsequent to perinatal hypoxia/ischemia.
Perinatal hypoxia/ischemia (H/I) is the leading cause of neurological injury resulting from birth complications and pre-maturity. Our studies have demonstrated that this injury depletes the subventricular zone (SVZ) of progenitors. In this study, we sought to reveal which cell death pathways are activated within these progenitors after H/I. We found that calpain activity is detected as early as 4 h of reperfusion and is sustained for 48 h, while caspase 3 activation does not occur until 8 h and peaks at 24 h post-insult. Activated calpains and caspase 3 co-localized within precursors situated in the lateral aspects of the SVZ (which coincides with progenitor cell death), whereas neither enzyme was activated in the medial SVZ (which harbors the neural stem cells that are resilient to this insult). These studies reveal targets for neuroprotective agents to protect precursors from cell death towards the goal of restoring normal brain development after H/I.
Romanko
Michael J
MJ
Molecular Medicine Graduate Program, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
Zhu
Changlian
C
Bahr
Ben A
BA
Blomgren
Klas
K
Levison
Steven W
SW
D000818:Animals; D000831:Animals, Newborn; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D005311:Fetal Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000503:physiopathology; D020547:Lateral Ventricles / Q000196:embryology; D008297:Male; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000378:metabolism*; D013687:Telencephalon / Q000196:embryology / Q000378:metabolism* / Q000503:physiopathology
D051017:Apoptosis Regulatory Proteins; D002154:Calpain; D053148:Caspase 3