Effect of hemorrhagic shock on apoptosis and energy-dependent efflux system in the brain.
Recent findings suggest that apoptosis, which contributes to neuronal damage after ischemic injury, may play a role in sequelae associated with severe blood loss. This study examined the effect of hemorrhage and resuscitation on the expression (in situ hybridization and computerized image analysis) of bcl-2 mRNA, which codes for a protein that inhibits apoptosis, and mdr1 mRNA, which codes for a glycoprotein marker for drug efflux from the brain. Anaesthetized rats were subjected to volume-controlled (15 mL/kg) hemorrhage followed by resuscitation with shed blood (BR) or nonresuscitated (NR); control animals had femoral artery cannulation only (SHAM). Following 24 hr blood loss, distinctly lower levels of bcl-2 gene expression were observed in dentate gyrus of NR rats (0.25 +/- 0.04) as compared to SHAM rats (0.52 +/- 0.07); suscitation with shed blood prevented this reduction (0.58 +/- 0.05). Similar results were observed in cortex, striatum, and hypothalamus. Also, mdr1 mRNA levels were significantly reduced in all brain areas of the NR group as compared to the BR and SHAM groups. The findings suggest that blood resuscitation suppressed apoptosis and protected against loss of energy-dependent efflux system in the brain in response to hemorrhage.
Yu
Zhao-Ying
ZY
Resuscitative Medicine Department, Naval Medical Research Center, Silver Spring, Maryland 20910, USA.
Ono
Shinsuke
S
Spatz
Maria
M
McCarron
Richard M
RM
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000378:metabolism / Q000473:pathology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger