Differential expression of insulin-like growth factor binding proteins (IGFBP) 4 and 5 mRNA in the rat brain after transient hypoxic-ischemic injury.
Recent studies suggest a role for the insulin-like growth factor (IGF) system in the repair of damaged tissue following hypoxic-ischemic injury in the infant rat brain. We have used a unilateral model of hypoxic-ischemic injury to assess the possible involvement of two IGF binding proteins (IGFBPs), IGFBP-4 and IGFBP-5, in the post-asphyxial response. Ligation of the right carotid artery of 21-day-old rats was followed by either 15 min or 60 min exposure to 8% oxygen to produce moderate and severe damage respectively. Using in situ hybridization, the distribution of IGFBP-4 and IGFBP-5 mRNA was determined in brains collected over 10 days following the insult. In the control brains (no damage), both IGFBPs were expressed in distinct regions. IGFBP-4 mRNA was detected in limited areas of the hippocampus and in several cortical layers, while IGFBP-5 mRNA was found primarily in the thalamus. In response to hypoxic-ischemic injury, IGFBP-4 mRNA expression was reduced in regions of neuronal loss, suggesting a neuronal origin for IGFBP-4. The expression of IGFBP-5 mRNA was not altered by the 15 min insult, but was heavily induced from 3 days following the 60 min insult, particularly in the subependymal layer and adjacent white matter on the ligated hemisphere. This suggests that IGFBP-5 may be involved in recovery from severe hypoxic-ischemic injury and may be important in the regeneration of oligodendrocytes.
Beilharz
E J
EJ
Research Centre for Developmental Medicine and Biology, University of Auckland, New Zealand.
Klempt
N D
ND
Klempt
M
M
Sirimanne
E
E
Dragunow
M
M
Gluckman
P D
PD
D000818:Animals; D001345:Autoradiography; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D015342:DNA Probes; D002534:Hypoxia, Brain / Q000378:metabolism*; D017403:In Situ Hybridization; D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D012313:RNA / Q000302:isolation & purification; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013002:Somatomedins / Q000378:metabolism; D013462:Sulfur Radioisotopes; D013997:Time Factors
D002352:Carrier Proteins; D015342:DNA Probes; D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D012333:RNA, Messenger; D013002:Somatomedins; D013462:Sulfur Radioisotopes; D012313:RNA