Microglia dysfunction drives disrupted hippocampal amplitude of low frequency after acute kidney injury

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.

Automated summary

In this study, resting-state functional magnetic resonance imaging (rs-fMRI) was used to detect early brain injury in acute kidney injury (AKI) rats and investigate the impact of microglia on the neuropathological mechanism of AKI. The results showed that AKI led to a decreased amplitude of low-frequency fluctuations (ALFF) in the hippocampus, especially at 48 h and 72 h. AKI activated the aggregation of microglia into neurons at 24 h, with a peak at 48 h, accompanied by the release of proinflammatory cytokines. The study demonstrated that microglia aggregation and inflammatory factor upregulation are significant mechanisms of AKI-induced neuronal apoptosis.