5-(N-Ethyl-N-isopropyl)-amiloride, an Na(+)-H(+) exchange inhibitor, protects gerbil hippocampal neurons from ischemic injury.
The effect of the selective Na(+)/H(+) antiporter inhibitor 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) on cerebral ischemia/reperfusion injury was evaluated in the Mongolian gerbil. Ischemia was induced in unanaesthetized gerbils by a 5-min period of bilateral common carotid artery occlusion followed by reperfusion for 6 days. Two groups of gerbils were injected intraperitoneally with either dimethyl sulfoxide (DMSO; 10 microl) or EIPA (5 mg/kg in 10 microl DMSO) 30 min prior to ischemia. The increase in locomotor activity in the EIPA-treated group was significantly less than that of the control group at both 24 h and 6-day post-ischemia. The extent of CA1 pyramidal neuron loss was significantly reduced in the EIPA-treated group in comparison with that of DMSO treated controls. These results suggest that EIPA can protect cerebral neurons from ischemia/reperfusion injury and implicates acidosis and Na(+)/H(+) exchange as a causative factor in such injury.
Phillis
J W
JW
Department of Physiology, Wayne State University School of Medicine, 540 E. Canfield Ave., Detroit, MI 48201, USA. jphillis@med.wayne.edu
Estevez
A Y
AY
Guyot
L L
LL
O'Regan
M H
MH
D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002545:Brain Ischemia / Q000517:prevention & control*; D005849:Gerbillinae; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000517:prevention & control*; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*
D018696:Neuroprotective Agents; D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride; C039614:ethylisopropylamiloride