MK-801 is neuroprotective but does not improve survival in severe forebrain ischemia.
The effects of MK-801 on postischemic recovery, survival and neuronal preservation in the cortex, hippocampus and striatum were studied in Mongolian gerbils. The drug was administered 30 min prior to 20 of min forebrain ischemia induced by bilateral ligation of the carotids. Neurological recovery and survival were monitored for 7 days. At the end of the monitoring period neuronal damage was analyzed in the brains of the survivors in both groups. Treatment with MK-801 did not improve either neurological recovery or end-point survival. However, significant (P < 0.01) neuronal protection was observed in the hippocampi and striata of the drug treated animals while cortical neurons were not significantly protected. These findings demonstrate that protection against ischemic neuronal damage can be observed without concomitant improvement in either postischemic neurological recovery or survival. Protection of selectively vulnerable brain regions, often used as the predictor of the therapeutic potential of an agent, does not appear to correlate well with postischemic survival in this animal model of ischemia.
Von Lubitz
D K
DK
Department of Biochemistry, Hahnemann University, Philadelphia, PA.
McKenzie
R J
RJ
Lin
R C
RC
Devlin
T M
TM
Skolnick
P
P
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000627:therapeutic use*; D005260:Female; D005557:Formaldehyde; D005849:Gerbillinae; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009474:Neurons / Q000187:drug effects*
D005557:Formaldehyde; D016291:Dizocilpine Maleate