An analysis of four different methods of producing focal cerebral ischemia with endothelin-1 in the rat.
Endothelin-1 (ET-1), a potent vasoconstrictor, reduces local blood flow to levels that produce ischemic injury when injected directly into brain tissue. The purpose of this study was to compare 4 different methods of inducing focal ischemia with ET-1: (1) topical application to the forelimb motor region of the cortex, (2) intracerebral injection into the forelimb motor region of the cortex, (3) a combination of intracortical and intrastriatal injections and 4. injection of ET-1 adjacent to the middle cerebral artery (MCA). We examined the effect of delivery method and dose of ET-1 on lesion size, inter-animal variability and behavioral outcome on 3 separate tests of motor function and limb preference. We calculated success rate as the percentage of animals that survived surgery and developed a significant impairment (>20% decrease in performance post-surgery) in the staircase-reaching test. All 4 methods produced similar deficits in the staircase, balance beam, and cylinder tests, but the application of ET-1 adjacent to the MCA, though widely used, provided the lowest success rate. The combined cortical and striatal ET-1 produced a high success rate and consequently we examined cerebral blood flow (CBF), the apparent diffusion coefficient (ADC) and T2-weighted magnetic resonance imaging (MRI) changes for this model. We found that infarct volume measured using T2-weighted MRI correlated with histological measurements and that ADC and CBF together predicted which areas will suffer permanent injury. The combined cortical and striatal injection model offers a number of advantages for studies of recovery of function.
Windle
Victoria
V
Basic Medical Sciences, Faculty of Medicine, Memorial University, St John's, NL, Canada.
Szymanska
Aleksandra
A
Granter-Button
Shirley
S
White
Chistopher
C
Buist
Richard
R
Peeling
James
J
Corbett
Dale
D
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D020520:Brain Infarction / Q000139:chemically induced / Q000473:pathology; D002545:Brain Ischemia / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D004333:Drug Administration Routes; D019332:Endothelin-1 / Q000008:administration & dosage / Q000633:toxicity*; D007267:Injections / Q000379:methods; D007276:Injections, Intraventricular; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009044:Motor Cortex / Q000187:drug effects / Q000503:physiopathology; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans
D019332:Endothelin-1