Correlation between tissue depolarizations and damage in focal ischemic rat brain.
Ischemia-induced depolarizations may play a key role in the development of cerebral ischemic injury. Our goal was to assess the relationship between tissue depolarizations and tissue damage in focal ischemia. We performed multi-electrode cortical direct current (DC) potential recording and, subsequently, diffusion-weighted and T(2)-weighted magnetic resonance imaging (MRI) in rats after i) cortical application of KCl, and ii) permanent and transient middle cerebral artery (MCA)-occlusion in rats. Cortical KCl application induced 10.0+/-2.2 transient negative DC potential shifts per h on the ipsilateral hemisphere (i.e. cortical spreading depressions) (n=4). During 6 h of permanent MCA-occlusion (n=9) 1-10 DC potential shifts were observed, dependent on the brain location. Anoxic depolarization developed in the ischemic core. Outside ischemic areas DC potential shifts resembled cortical spreading depressions. Depolarizations in cortical ischemic borderzones were also transient, but generally long-lasting. Reperfusion induced 1 (n=5) or 3 h (n=6) after MCA-occlusion resulted in repolarization in 2.9+/-1.5 min. Ischemic lesion volumes after 7 h, calculated from diffusion-weighted and T(2)-weighted MR images, correlated significantly with total depolarization time in cortical perifocal zones (R=0.741, p<0.05), but not with the number of depolarizations. The extent of ischemic damage, as measured from alterations in the water diffusion coefficient and T(2), was also significantly related to the total time of depolarization (R=0.762 and 0.738, respectively, p<0.01). We conclude that early ischemic tissue injury is related to the total duration of tissue depolarization and not to the frequency of depolarizations.
Dijkhuizen
R M
RM
Department of Neurosurgery, University Hospital Utrecht, Utrecht, The Netherlands. rickd@NMR.MGH.Harvard.edu
Beekwilder
J P
JP
van der Worp
H B
HB
Berkelbach van der Sprenkel
J W
JW
Tulleken
K A
KA
Nicolay
K
K
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D002545:Brain Ischemia / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology*; D013181:Cortical Spreading Depression; D004594:Electrophysiology; D002546:Ischemic Attack, Transient / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology
D011189:Potassium Chloride