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 (DM TU), an established free radical scavenger, ameliorates ischaemic dama ge due to 2-3 h of transient middle cerebral artery (MCA) occlusion, i nduced by an intraluminal filament. A major point adressed was whether DMTU given before MCA occlusion only delayed the ''maturation'' of th e damage, or if it had a lasting effect on infarct size. The end point was morphological, and either encompassed triphenyltetrazolium chlori de (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 b y 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 t issue damage was observed. However, since DMTU reduced a spontaneous r ise in body temperature to 39.0-39.5-degrees-C, DMTU-treated animals i n the main series of experiments with 24 and 48 h of recovery were tre ated 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 la ck of a lasting effect of DMTU was supported by the findings on evalua tion of infarct area after 7 days of recovery. The results raise the i mportant question whether DMTU, and perhaps other free radical scaveng ers, delay rather than ameliorate the ischaemic lesion developing afte r transient MCA occlusion.