山梨医科大学雑誌　第10巻2号　057-069(1995)

Effect of H-7 on Cerebral Ischemia: Evaluated by Diffusion Weighted MR Imaging

Mohammad Zakir HUSSAIN, Hideo NISHI, Kuni OHTTOMO, Tsutomu HOSAKA, Eikoh ITOH, Guio UCHIYAMA and Tsutomu ARAKI

Abstract: Purpose: To determine whether the apparent diffusion coefficient (ADC) value is useful in interpreting the effect of H-7 [1, 5 (iso-quinolinyl sulfonyl)-2-methyl piperazine] on brain Ischemia and to investigate the drug's effect on formation of brain edema in vivo.
Materials and methods: H-7 was investigated for its effect on brain ischemia by diffusion weighted imaging (DWI) and T2-weighted imaging (T2WI). We used magnetic resonance (MR) apparatus and measured ADC values of ischemic lesions of 6 rats treated with this drug and those without treatment 2, 4, 6 and 12 hours after middle cerebral artery occlusion (MCAO) (n=6). Another 15 rats were studied for determination of histopathological changes after MCAO. Ten rats were sacrificed at 6 hr (5 untreated and 5 treated) and 5 rats at 12 hr (3 untreated and 2 treated) after MCAO.
Results: The mean ADC values were higher in the treated rats at 2, 4 and 6 hr after MCAO and the differences in ADC values compared to control group were significant (Mann-Whitney U test, P<0.05), in both cortex and caudate lesions, while the values decreased in the treated rats at 12 hours and became lower than those in the untreated group (p<0.05). Histopathologically, both treated and untreated specimens showed severe edema with marked cellular swelling recognized as vacuolation in the nerve cells and astrocytes. There was no histopathological difference between the two groups.
Conclusion: ADC measurement may be used to assess the effect of drugs which affect the brain responses to ischemia. Conventional histopathological examinations did not reveal effects of H-7 on cerebral ischemia. Further studies dealing with the correlations among the histochemical, ultrastructural and DWI studies may be necessary.

Key words: H-7, cerebral ischemia, ADC (apparent diffusion coefficient), diffusion weighted imaging and MR




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