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.
Sydserff
S G
SG
Astra Neuroscience Research Unit, London.
Green
A R
AR
Cross
A J
AJ
D000818:Animals; D001834:Body Water; D001921:Brain / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D001929:Brain Edema / Q000503:physiopathology* / Q000517:prevention & control; D002545:Brain Ischemia / Q000503:physiopathology* / Q000517:prevention & control; D002536:Cerebral Arteries / Q000502:physiology*; D002719:Chlormethiazole / Q000494:pharmacology*; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012044:Regression Analysis
D018696:Neuroprotective Agents; D002719:Chlormethiazole