Secondary energy failure after cerebral hypoxia-ischemia in the immature rat.
A delayed or secondary energy failure occurs during recovery from perinatal cerebral hypoxia-ischemia. The question remains as to whether the energy failure causes or accentuates the ultimate brain damage or is a consequence of cell death. To resolve the issue, 7-day postnatal rats underwent unilateral common carotid artery occlusion followed thereafter by systemic hypoxia with 8% oxygen for 2.5 hours. During recovery, the brains were quick frozen and individually processed for histology and the measurements of 1) high-energy phosphate reserves and 2) neuronal (MAP-2, SNAP-25) and glial (GFAP) proteins. Phosphocreatine (PCr) and ATP, initially depleted during hypoxia-ischemia, were partially restored during the first 18 hours of recovery, with secondary depletions at 24 and 48 hours. During the initial recovery phase (6 to 18 hours), there was a significant correlation between PCr and the histology score (0 to 3), but not for ATP. During the late recovery phase, there was a highly significant correlation between all measured metabolites and the damage score. Significant correlation also exhibited between the neuronal protein markers, MAP-2 and SNAP-25, and PCr as well as the sum of PCr and Cr at both phases of recovery. No correlation existed between the high-energy reserves and the glial protein marker, GFAP. The close correspondence of PCr to histologic brain damage and the loss of MAP-2 and SNAP-25 during both the early and late recovery intervals suggest evolving cellular destruction as the primary event, which precedes and leads to the secondary energy failure.
Vannucci
Robert C
RC
Department of Pediatrics, The Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, USA. robert.vannucci@verizon.net
Towfighi
Javad
J
Vannucci
Susan J
SJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D003401:Creatine / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D015415:Biomarkers; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D003401:Creatine