The Effect of Oedema and Tissue Swelling on the Measurement of Neuroprotection; a Study using Chlormethiazole and Permanent Middle Cerebral Artery Occlusion in Rats

The effect of chlormethiazole on hemispheric swelling and cortical tissue water content has been investigated in a model of permanent middle cerebral artery (MCA) occlusion. Chlormethiazole (1 mmol/kg i.p.) or saline was administered 60 min after the induction of ischaemia and the animals sacrificed after 24 hours. The cross sectional area of the left hemisphere was increased by 21.8 + 1.9 % in saline treated rats, but only by 8.4 + 2.4% in chlormethiazole treated rats. However, the reduction in the absolute area of neurodegenerative damage (mm²) following chlormethiazole administration was considerably greater than the reduction in hemispheric swelling. Cortical tissue water content of ischaemic brain increased from 76.4% to 84.2% and this was attenuated to 78.8% by chlormethiazole administration. These data demonstrate that, providing damage is measured by fitting tissue slices onto prematched stereotactic maps, the decrease in oedema which accompanies a decrease in neurodegeneration does not result in erroneous estimates of neuroprotection.