Effects of intravenous dimethyl sulfoxide on ischemia evolution in a rat permanent occlusion model.
Dimethyl sulfoxide (DMSO) has a variety of biological actions that suggest efficacy as a neuroprotectant. We (1) tested the neuroprotective potential of DMSO at different time windows on infarct size using 2,3,5-triphenyltetrazolium staining and (2) investigated the effects of DMSO on ischemia evolution using quantitative diffusion and perfusion imaging in a permanent middle cerebral artery occlusion (MCAO) model in rats. In experiment 1, DMSO treatment (1.5 g/kg intravenously over 3 h) reduced infarct volume 24 h after MCAO by 65% (P<0.00001) when initiated 20 h before MCAO, by 44% (P=0.0006) when initiated 1 h after MCAO, and by 17% (P=0.11) when started 2 h after MCAO. Significant infarct reduction was also observed after a 3-day survival in animals treated 1 h after MCAO (P=0.005). In experiment 2, treatment was initiated 1 h after MCAO and maps for cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) were acquired before treatment and then every 30 mins up to 4 h. Cerebral blood flow characteristics and CBF-derived lesion volumes did not differ between treated and untreated animals, whereas the ADC-derived lesion volume essentially stopped progressing during DMSO treatment, resulting in a persistent diffusion/perfusion mismatch. This effect was mainly observed in the cortex. Our data suggest that DMSO represents an interesting candidate for acute stroke treatment.
Bardutzky
Juergen
J
Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, USA. juergen_bardutzky@med.uni-heidelberg.de
Meng
Xianjun
X
Bouley
James
J
Duong
Timothy Q
TQ
Ratan
Rajiv
R
Fisher
Marc
M
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D038524:Diffusion Magnetic Resonance Imaging; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage / Q000627:therapeutic use*; D018450:Disease Progression; D007839:Functional Laterality / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000150:complications* / Q000473:pathology; D007275:Injections, Intravenous; D008297:Male; D018696:Neuroprotective Agents; D051381:Rats; D011921:Rats, Inbred WKY
D018696:Neuroprotective Agents; D004121:Dimethyl Sulfoxide
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