Correlation between changes in apparent diffusion coefficient and induction of heat shock protein, cell-specific injury marker expression, and protein synthesis reduction on diffusion-weighted magnetic resonance images after temporary focal cerebral ischemia in rats

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Object. The authors investigated the relationship between the time course of apparent diffusion coefficient (ADC) changes and stress protein induction, ischemic neuroglial damage, and cerebral protein synthesis (CPS) after temporary focal cerebral ischemia in rats.

Methods. In Group I, ADC changes were measured on magnetic resonance (MR) images obtained during the second half of a 1-hour middle cerebral artery (MCA) occlusion, during a 1-hour reperfusion, and after 23 hours of reperfusion in rats. Immunohistochemical studies for heat shock protein (hsp) 70, glial fibrillary acidic protein (GFAP), and neuronal nuclear (NeuN) protein were performed. In Group II, CPS was assessed using autoradiographic studies obtained after occlusion.

At 36 minutes of occlusion, MR imaging demonstrated significantly less ADC reduction in the frontoparietal cortex (82 ± 9% of the contralateral hemisphere) than in the striatum (64 ± 11%; p < 0.05). After 1 hour of reperfusion, the lesion resolved and the difference between cortex and striatum was no longer evident. After 23 hours of reperfusion, the ADC lesion recurred in striatum (76 ± 12%) compared with frontoparietal cortex (100 ± 11%; p < 0.05). Immunohistochemical studies showed hsp 70 expression and an increased GFAP reactivity localized in the frontoparietal cortex of the ischemic hemisphere, along with a significant drop in striatal NeuN immunoreactivity. A trend toward greater reduction in striatal CPS (53 ± 15%) than in frontoparietal cortex CPS (78 ± 23%) was also observed.

Conclusions. Sequential ADC maps correlate with the expression of neuroglial stress and injury markers after temporary focal ischemia in rats, distinguishing the striatum (infarct core) from the cortex (ischemic penumbra). A greater reduction in striatal CPS further supports the conclusion that the striatum is more susceptible to temporary MCA occlusion than the cortex.

Article Information

Contributor Notes

Address reprint requests to: Philip R. Weinstein, M.D., Department of Neurological Surgery, 787-M University of California, San Francisco, California 94143. email: weinsteinp@neuro.ucsf.edu.
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