Free radicals and brain damage due to transient middle cerebral artery occlusion: the effect of dimethylthiourea.
The objective of this study was to assess whether dimethylthiourea (DMTU), an established free radical scavenger, ameliorates ischaemic damage due to 2-3 h of transient middle cerebral artery (MCA) occlusion, induced by an intraluminal filament. A major point addressed was whether DMTU given before MCA occlusion only delayed the "maturation" of the damage, or if it had a lasting effect on infarct size. The end point was morphological, and either encompassed triphenyltetrazolium chloride (TTC) staining of tissue slices after 24 h or 48 h of recovery, or histopathological assessment of infarct size after 7 days of recovery. In a preliminary series of experiments, rats were subjected to 3 h of MCA occlusion, and infarct volume was assessed by TTC staining after 24 h of recovery. DMTU in a dose of 750 mg/kg reduced infarct volume by more than 50%. However, due to a high mortality rate, that protocol was not subsequently pursued. When the ischaemia duration was reduced to 2 h and the DMTU dose to 400 mg/kg, a similar amelioration of the tissue damage was observed. However, since DMTU reduced a spontaneous rise in body temperature to 39.0-39.5 degrees C, DMTU-treated animals in the main series of experiments with 24 and 48 h of recovery were treated so that they had the same temperature rise as the saline controls. Under such constant temperature conditions, the effect of DMTU at 24 h of recovery was borderline (P = 0.052) and at 48 h it was nil. The lack of a lasting effect of DMTU was supported by the findings on evaluation of infarct area after 7 days of recovery. The results raise the important question whether DMTU, and perhaps other free radical scavengers, delay rather than ameliorate the ischaemic lesion developing after transient MCA occlusion.
Kiyota
Y
Y
Laboratory for Experimental Brain Research, University Hospital, Lund, Sweden.
Pahlmark
K
K
Memezawa
H
H
Smith
M L
ML
Siesjö
B K
BK
D000818:Animals; D001831:Body Temperature / Q000502:physiology; D002536:Cerebral Arteries / Q000502:physiology*; D002544:Cerebral Infarction / Q000473:pathology / Q000517:prevention & control; D005609:Free Radicals / Q000378:metabolism; D006651:Histocytochemistry; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D010078:Oxazines; D051381:Rats; D017208:Rats, Wistar; D012394:Rosaniline Dyes; D013194:Staining and Labeling; D013778:Tetrazolium Salts; D013890:Thiourea / Q000031:analogs & derivatives* / Q000627:therapeutic use
D005609:Free Radicals; D010078:Oxazines; D012394:Rosaniline Dyes; D013778:Tetrazolium Salts; C009591:triphenyltetrazolium; C038983:1,3-dimethylthiourea; D013890:Thiourea; C007063:Celestine Blue