Application of 9.4 Tesla resting-state functional MRI to Assess Neuronal function and Detect Microglial Density in AKI Rat Model

Abstract Background Converging evidence increasingly implicates acute kidney injury (AKI) contribute to a series of brain injury. However, the neurobiological mechanisms of AKI induced brain alterations remains unclear. Examining the neurobiology of AKI induce brain injury and an early detection using non-invasive imaging method is critical for the early diagnosis and target treatment. Methods The AKI Sprague-Dawley male rats and the healthy control group performed the Morris water maze and acquired rs-fMRI images with 9.4-Tesla Bruker BioSpec system at 24, 48 and 72 hours following administering contrast medium or saline. Whole brain amplitude of Low-Frequency Fluctuations (ALFF) at each time course was compared among groups. The AKI rats were then euthanized immediately, followed by H&E staining and immunohistochemistry (IHC). Besides, Flow cytometry analysis, Western blotting and immunofluorescence were performed to evaluate neuron and activated microglia. Results In contrast to HC group, lower ALFF in bilateral Cornu Ammonis (CA1) were observed in AKI-CI group. Specifically, there were significant differences in the ALFF values in the CA1 between the 48 h and 72 h in AKI groups. In addition, the percentages of microglia increased in AKI group at 24 h (range from 15.07 to 41.70%) and dramatically increased after 24h (range from 41.70–82.57%). Moreover, quantitative Flow cytometry analysis of microglial proportion is strongly correlated with the mALFF value (|r|༞0.80, P༜0.001). Conclusions Aberrant functional activity in the hippocampus, mainly CA1, contributes to the AKI induced brain injury. The ALFF of hippocampus may be an effective imaging biomarker for detecting grading of microglial proportion and have implications for early target treatment.