Prostaglandin H synthase-2 and cytosolic phospholipase A2 in the hypoxic-ischemic brain: role in neuronal death or survival?
The breakdown of membrane phospholipids and subsequent arachidonic acid metabolism to prostanoids is a well-documented brain response to cerebral ischemia. To further elucidate the components of this signal transduction pathway, immunocytochemistry was used to determine the levels of two potentially important enzymes, cytosolic phospholipase A2 (cPLA2) and prostaglandin H synthase-2 (PGHS-2), in the immature rat brain following moderate unilateral hypoxic-ischemia (HI). The CA1 pyramidal cells of the hippocampus which undergo delayed neuronal death on the injured side following HI demonstrated a significant induction of PGHS-2 immunoreactivity 48 h post-insult. However, a consistent increase in PGHS-2 was also evident in the resistant dentate granule cells at an earlier time point. Although PGHS-2 is present in both susceptible and resistant cell populations following HI, the possibility remains that divergence further down-stream in the pathway is responsible for selective vulnerability. In contrast to the neuronal PGHS-2 expression, cPLA2 immunoreactivity appears to be of glial origin with increases in and around the CAI-2 pyramidal cell layer at the 72-168-h time points. These results suggest that prostanoids are likely to serve important roles in HI brain damage and repair in infant brain.
Walton
M
M
Department of Pharmacology, Faculty of Medicine and Health Science, University of Auckland, New Zealand.
Sirimanne
E
E
Williams
C
C
Gluckman
P D
PD
Keelan
J
J
Mitchell
M D
MD
Dragunow
M
M
D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology* / Q000473:pathology; D016923:Cell Death / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D003600:Cytosol / Q000201:enzymology*; D006624:Hippocampus / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D002534:Hypoxia, Brain / Q000201:enzymology* / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D018715:Microscopy, Video; D009474:Neurons / Q000473:pathology*; D010741:Phospholipases A / Q000502:physiology*; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2