Reversal of early diffusion-weighted magnetic resonance imaging abnormalities does not necessarily reflect tissue salvage in experimental cerebral ischemia

Background and Purpose-Diffusion-weighted MRI (DWI) can detect early ischem ic changes and is sometimes used as a surrogate neurological end point in c linical trials. Recent experimental stroke studies have shown that with bri ef periods of ischemia, some DWI lesions transiently reverse, only to recur later. This study examined the histological condition of the tissue during the period of DWI reversal. Methods-Rats underwent 30 minutes of middle cerebral artery occlusion follo wed by reperfusion. DWI images were obtained during ischemia and 3 to 5 hou rs, 1 day, and 7 days later. MRI scans were compared with histology (5 hour s, n=5; 7 days, n=5) with the use of neuronal (microtubule-associated prote in 2 [MAP2]) and astrocytic (glial fibrillary acidic protein [GFAP]) marker s and heat-shock protein 72 (HSP72). Results-DWI abnormalities reversed 3 to 5 hours after ischemia onset but re curred at 1 day. Four animals showed complete reversal of the initial DWI h yperintensity, and 6 showed partial reversal. When the 5-hour DWI was compl etely normal, there was significant loss of MAP2 immunoreactivity, comprisi ng approximately 30% of the initial DWI lesion. However, GFAP staining reve aled morphologically normal astrocytes. HSP72 immunoreactivity at 5 hours w as extensive and corresponded to the initial DWI lesion. Conclusions-After brief ischemic periods, normalization of the DWI does not necessarily imply that the tissue is normal. Neurons already exhibit evide nce of structural damage and stress. Normal GFAP staining suggests that oth er nonneuronal cell populations may partially compensate for altered fluid balances at the time of DWI reversal despite the presence of neuronal injur y. These observations suggest that caution is warranted when relying solely on DWI for assessment of ischemic damage.