STZ-induced Progressive Brain Atrophy Studied By Magnetic Resonance Imaging And Histochemistry

Type1diabetes mellitus (T1DM) is a kind of chronic metabolic disease, which is characterized as insulin deficiency and usually causes persistent damage to multiple organs and systems of body. Many cross-sectional, retrospective studies found that, compared to normal subject, type1diabetic patients showed significant cerebral atrophy. But few of the studies investigated the progressive change of cerebral atrophy over time. In our lab, former study reported significant cerebral atrophy of type1diabetic rats at4th week after STZ injection. In this study, we investigated the cerebral atrophy over a longer time span, and focused on the progression of cerebral atrophy.First we established a rat model of type1diabetes mellitus by intraperitoneal injection (i.p.) of streptozotocin (STZ). Then we acquired the magnetic resonance imaging (MRI) data at12th and20th week after STZ injection, and brain volume and volume changes over time were analyzed by voxel-based morphometry (VBM) method. After that, rats were decapitated and brain sections were obtained to investigate the neuron loss in the regions with progressive atrophy.Based on high resolution rapid acquisition with relaxation enhancement (RARE) sequence and voxel-based morphometry analysis, we found that STZ-treated rats, at both12w and20w, showed significant reduced total volume of grey matter (GM), white matter (WM) and the whole brain, as compared to the control rats. Voxel-wise two-way ANOVA revealed significant effect of groupxtime interaction in multiple GM and WM regions. Based on the result of MRI, we adopted the Nissl staining and hematein-eosin staining (HE) to investigate the brain regions observed in MRI. In somatosensory cortex, motor cortex and hippocampal CA3region of STZ-treated rats, we found significant neuron apopotosis, which was unconspicous in control rats.In conclusion, we found significant cerebral atrophy in STZ treated rats, compared to the control rats, and such cerebral atrophy showed significant progressive change over time in multiple brain regions. The consistency of MRI and immunohistochemistry results infer that the significant effect of group xtime interaction observed in MRI might be caused by neuron loss in these brain regions.