Diazoxide and dimethyl sulphoxide alleviate experimental cerebral hypoperfusion-induced white matter injury in the rat brain.
Aging and dementia are accompanied by cerebral white matter (WM) injury, which is considered to be of ischemic origin. A causal link between cerebral ischemia and WM damage has been demonstrated in rats; however, few attempts appear to have been made to test potential drugs for the alleviation of ischemia-related WM injury. We induced cerebral hypoperfusion via permanent, bilateral occlusion of the common carotid arteries of rats. A mitochondrial ATP-sensitive potassium channel opener diazoxide (5 mg/kg) or its solvent dimethyl sulphoxide (DMSO) was administered i.p. (0.25 ml) on 5 consecutive days after surgery. Sham-operated animals served as control for surgery, and non-treated rats as controls for treatments. Thirteen weeks after surgery, the animals were sacrificed and astrocytes and microglia were labeled immunocytochemically in the internal capsule, the corpus callosum and the optic tract. The astrocytic proliferation was enhanced by cerebral hypoperfusion in the optic tract, and reduced by diazoxide in DMSO, but not by DMSO alone in the corpus callosum. After carotid artery occlusion, microglial activation was enhanced two-fold in the corpus callosum and four-fold in the optic tract. DMSO decreased microglial activation in the optic tract, while diazoxide in DMSO, but not DMSO alone, restored microglial activation to the control level in the corpus callosum. In summary, the rat optic tract appeared to be particularly vulnerable to ischemia, while the effect of diazoxide was restricted to the corpus callosum. We conclude that diazoxide dissolved in DMSO can moderate ischemia-related neuroinflammation by suppressing glial reaction in selective cerebral WM areas.
Farkas
Eszter
E
Department of Anatomy, School of Medicine, University of Szeged, P.O. Box 427, 6701 Szeged, Hungary. farkase@anat-fm.szote.u-szeged.hu
Annaházi
Anita
A
Institóris
Adám
A
Mihály
András
A
Luiten
Paul G M
PG
Bari
Ferenc
F
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology*; D003337:Corpus Callosum / Q000187:drug effects / Q000473:pathology; D003981:Diazoxide / Q000494:pharmacology / Q000627:therapeutic use*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014795:Visual Pathways / Q000187:drug effects / Q000473:pathology
D003981:Diazoxide; D004121:Dimethyl Sulfoxide