Apoptosis in perinatal hypoxic-ischemic brain injury: how important is it and should it be inhibited?
The discovery of safe and effective therapies for perinatal hypoxia-ischemia (HI) and stroke remains an unmet goal of perinatal medicine. Hypothermia and antioxidants such as allopurinol are currently under investigation as treatments for neonatal HI. Drugs targeting apoptotic mechanisms are currently being studied in adult diseases such as cancer, stroke, and trauma and have been proposed as potential therapies for perinatal HI and stroke. Before developing antiapoptosis therapies for perinatal brain injury, we must determine whether this form of cell death plays an important role in these injuries and if the inhibition of these pathways promotes more benefit than harm. This review summarizes current evidence for apoptotic mechanisms in perinatal brain injury and addresses issues pertinent to the development of antiapoptosis therapies for perinatal HI and stroke.
Northington
Frances J
FJ
Department of Pediatrics, Eudowood Neonatal Pulmonary Division, Dept. of Pediatrics, CMSC 6-104, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Baltimore, MD 21287, USA. frances@jhmi.edu
Graham
Ernest M
EM
Martin
Lee J
LJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology*; D008959:Models, Neurological; D015398:Signal Transduction / Q000502:physiology*