Differences in vulnerability to permanent focal cerebral ischemia among 3 common mouse strains.
OBJECTIVE
Genetically engineered mice are used to study the role of single genes in cerebral ischemia, but inherent, strain-dependent differences in neuronal vulnerability may affect experimental end points. To examine this possibility, tissue injury resulting from focal ischemia and its relationship to cerebral hemodynamics were determined in 3 common mutant mouse strains.


METHODS
Permanent middle cerebral artery ligation was performed in male C57BL/6J, Balb/C, and 129X1/SvJ mice. Mean arterial blood pressure, blood gases, basal and postischemic cortical blood flow ([(14)C]iodoantipyrine autoradiography and laser-Doppler flowmetry), posterior communicating artery patency, and infarct size were determined.


RESULTS
Basal cortical blood flow did not differ among strains. Ten minutes after middle cerebral artery ligation, relative red cell flow in the ischemic cortex was 6% to 7% of preischemic flow in every strain. Despite similar hemodynamics, cortical infarcts in Balb/C mice were 3-fold larger than those in 129X1/SvJ and C57BL/6J mice; infarct size in the latter 2 strains was not significantly different. The posterior communicating artery was either poorly developed or absent in >90% of the Balb/C and C57BL/6J but in <50% of the 129X1/SvJ mice.


CONCLUSIONS
The extent of ischemic injury differed markedly between the 3 strains. The presence and patency of posterior communicating arteries, although variable among strains, did not affect preischemic or postischemic cortical blood flow or bear any relationship to ischemic injury. Therefore, intrinsic factors, other than hemodynamic variability, may contribute to the differences in ischemic vulnerability among strains. These findings underscore the importance of selecting genetically matched wild-type controls.
Majid
A
A
Department of Neurology and Center for the Study of Nervous System Injury, Washington University School of Medicine, St Louis, MO, USA.
He
Y Y
YY
Gidday
J M
JM
Kaplan
S S
SS
Gonzales
E R
ER
Park
T S
TS
Fenstermacher
J D
JD
Wei
L
L
Choi
D W
DW
Hsu
C Y
CY
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives*; D001345:Autoradiography; D001784:Blood Gas Analysis; D002545:Brain Ischemia / Q000235:genetics*; D002244:Carbon; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000098:blood supply; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains / Q000235:genetics*; D012039:Regional Blood Flow; D012107:Research Design / Q000592:standards; D013045:Species Specificity
D002250:Carbon Radioisotopes; D002244:Carbon; D000983:Antipyrine; C008135:iodoantipyrine