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AimsAcute kidney injury (AKI) has been associated with a variety of neurological problems, while the neurobiological mechanism remains unclear. In the present study, we utilized resting‐state functional magnetic resonance imaging (rs‐fMRI) to detect brain injury at an early stage and investigated the impact of microglia on the neuropathological mechanism of AKI.MethodsRs‐fMRI data were collected from AKI rats and the control group with a 9.4‐Tesla scanner at 24, 48, and 72 h post administration of contrast medium or saline. The amplitude of low‐frequency fluctuations (ALFF) was then compared across the groups at each time course. Additionally, flow cytometry and SMART‐seq2 were employed to evaluate microglia. Furthermore, pathological staining and Western blot were used to analyze the samples.ResultsMRI results revealed that AKI led to a decreased ALFF in the hippocampus, particularly in the 48 h and 72 h groups. Additionally, western blot suggested that AKI‐induced the neuronal apoptosis at 48 h and 72 h. Flow cytometry and confocal microscopy images demonstrated that AKI activated the aggregation of microglia into neurons at 24 h, with a strong upregulation of M1 polarization at 48 h and peaking at 72 h, accompanying with the release of proinflammatory cytokines. The ALFF value was strongly correlated with the proportion of microglia (|r| > 0.80, p < 0.001).ConclusionsOur study demonstrated that microglia aggregation and inflammatory factor upregulation are significant mechanisms of AKI‐induced neuronal apoptosis. We used fMRI to detect the alterations in hippocampal function, which may provide a noninvasive method for the early detection of brain injury after AKI.

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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.