Measurement of Regional Tissue Water and Ionic Concentrations During the Evolution of Infraction and the Therapeutic Value of Nimodipine in Rat Middle Cerebral Artery Occlusion Model of Ischemia

ABSTRACT

The evolution of infarction in the rat middle cerebral artery(MCA) occlusion model was examined by atomic absorption spectrometric measurements of Na, K and Ca concentrations in brain tissue sample. At 2, 4, 6, 8, and 24 hours after MCA occlusion and sham occlusion the brain tissue samples were obtained. Tissue water concentrations were estimated from dry-wet weight measurement. The effects of nimodipine(2 microgram/kg/min for 10 min) administered intra-venously at 4 hours(Group A), 6 hours(Group B), and 9 hours(Group C) after MCA occlusion were investigated on both the size of infarction and tissue water, Na, K, Ca concentrations at 24 hours. The result were as follows 1) Normal concentrations of water, Na, K, and Ca averaged 0.793+/-0.009ml, 54.06+/-4.18 micromole, 81.04+/-3.44 micromole, and 3.578+/-0.712 micromole/gm wet weight. At the infarct site by 24 hours, the changes of tissue water and ionic concentrations were conspicuously evident so that water increased by more than 10%(p<0.005), Na increased by more than 120%(p<0.005), K decreased by more than 75%(p<0.005), and Ca increased by more than 200%(p<0.005). 2) The remarkable shifts of Na, K, and Ca concentrations occurred at 4-6 hours so that 60-85% of the ionic shifts developed by 6 hours. This characteristics of chronological ionic changes correlated well with the findings of 2% TTC staining during the evolution of infarction. Water concentrations increased rapidly at 2-4 hours so that nearly 80% of water shift developed by 4 hours. 3) In group A(administered at 4 hours), nimodipine treatment significantly reduced both the ionic shifts at the infarct site and the size of infarction compared with non-treated rats(p<0.05). 4) In group B(administered at 6 hours), nimodipine treatment did not significantly reduce the ionic shifts but did reduce the size of infarction compared with non-treated rats(p<0.05). In group C(administered at 8 hours), nimodipine treatment significantly reduce neither the ionic shifts nor the size of infarction. In summary it was concluded that the progressive changes in tissue water and ionic concentrations developed at the infarct sites and the critical period of the changes was between 4 and 6 hours, and nimodipine treatment was effective when administered within 4 hours. The results suggested that measurement of tissue ionic concentrations could be used as an alternative method for assessing tissue damage and a reliable method to quantify the tissue damage. This method may be useful for determining the time window for therapeutic protocol, as well as for evaluating therapeutic effects.