American Journal of Neuroradiology 23:180-188, February 2002
© 2002 American Society of Neuroradiology
BRAIN
Acute Postischemic Renormalization of the Apparent Diffusion Coefficient of Water is not Associated with Reversal of Astrocytic Swelling and Neuronal Shrinkage in Rats
a Department of Neurology, UMass Memorial Health Care and University of Massachusetts Medical School, Worcester
b Department of Radiology, UMass Memorial Health Care and University of Massachusetts Medical School, Worcester
c Department of Pathology, Neuropathology Section, Henry Ford Hospital, Detroit, MI
d Department of Anesthesiology, Henry Ford Hospital, Detroit, MI
e Department of Biomedical Engineering, Worcester Polytechnic Institute, MA
f Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, MA
Address reprint requests to Fuhai Li, MD, Department of Neurology, UMass Memorial Health Care, 119 Belmont Street (Memorial Campus), Worcester, MA 01605
BACKGROUND AND PURPOSE: Initially decreased apparent diffusion coefficient (ADC) values are reversible if reperfusion is rapidly performed after focal brain ischemia. We sought to determine if reperfusion-induced renormalization of initially abnormal values indicates reversal of cellular, morphologic changes that occur during acute ischemia.
METHODS: Eighteen rats underwent 30 minutes of middle cerebral artery occlusion (MCAO) without reperfusion (group A, n = 6), with 1.5 hours of reperfusion (group B, n = 6), or with 12 hours of reperfusion (group C, n = 6). Diffusion- and perfusion-weighted MR images were obtained at the end of MCAO and 1.5 and 12 hours after reperfusion. Immediately after the final MR study, the brains were fixed by cardiac perfusion with 4% paraformaldehyde. Neuronal injury was evaluated on hematoxylin-eosin-stained slices, and astrocytic size was determined by the area of glial fibrillary acidic protein (GFAP) plus S-100 expression.
RESULTS: In group A in which ADC values decreased significantly, 47 ± 12% of the neurons were slightly shrunken; astrocytes were moderately swollen, and the area expressing GFAP plus S-100 was larger than that in the contralateral hemisphere (117 µm2 ± 6 vs 89 µm2 ± 2; P < .001). In group B in which ADC had renormalized, most neurons were moderately shrunken, and the frequency of such neurons was greater in group B (92% ± 2) than in group A (P < .001); astrocytes were markedly swollen, and the area was larger than that in the contralateral hemisphere (123 µm2 ± 8 vs 85 µm2 ± 4, P < .001). In group C in which a secondary ADC decrease occurred, most neurons (94% ± 3) were severely shrunken, and some had eosinophilic cytoplasm; astrocytes were disintegrated, and the area of GFAP plus S-100 expression was reduced (78 µm2 ± 4 vs 90 µm2 ± 5, P < .001).
CONCLUSION: Reperfusion-induced acute renormalization of ADC values is not associated with the reversal of neuronal shrinkage and astrocytic swelling that occur during ischemia. Conversely, the morphologic changes of astrocytes and neurons progressively worsen over time, although ADC values show a biphasic change.
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