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Updated: Jul 23, 2025
Investigations on Alterations of Hippocampal Circuit Function Following Mild Traumatic Brain Injury
Published on: November 19, 2012
Microglia dysfunction drives disrupted hippocampal amplitude of low frequency after acute kidney injury
Ziyang Yu1, Huize Pang2, Yifan Yang1
1School of Medicine, Xiamen University, Xiamen, China.
Aims:
Acute 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.
Methods:
Rs-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.
Results:
MRI 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).
Conclusions:
Our 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.
Insights
Acute kidney injury (AKI) causes brain injury by activating microglia and increasing inflammation, leading to neuronal apoptosis. Resting-state fMRI can detect these early hippocampal changes in AKI.
Area of Science:
- Neuroscience
- Nephrology
- Radiology
Background:
- Acute kidney injury (AKI) is linked to neurological deficits, but the underlying neurobiological mechanisms are not fully understood.
- Investigating early brain changes in AKI is crucial for timely intervention and improved patient outcomes.
Purpose of the Study:
- To investigate the neurobiological mechanisms of AKI-induced brain injury using resting-state functional magnetic resonance imaging (rs-fMRI).
- To examine the role of microglia activation and inflammatory responses in the neuropathology of AKI.
- To assess the potential of rs-fMRI for early detection of brain injury in AKI.
Main Methods:
- Collected rs-fMRI data from AKI and control rats at 24, 48, and 72 hours post-induction.
- Analyzed the amplitude of low-frequency fluctuations (ALFF) in the hippocampus.
- Utilized flow cytometry, SMART-seq2, Western blot, and pathological staining to evaluate microglia and neuronal apoptosis.
Main Results:
- AKI induced decreased hippocampal ALFF at 48 and 72 hours, correlating with neuronal apoptosis.
- Microglia aggregated around neurons by 24 hours, with M1 polarization peaking at 72 hours, releasing proinflammatory cytokines.
- A strong correlation was found between hippocampal ALFF and microglia proportion (|r| > 0.80, p < 0.001).
Conclusions:
- Microglia aggregation and inflammatory factor upregulation are key mechanisms in AKI-induced neuronal apoptosis.
- rs-fMRI can detect functional alterations in the hippocampus, offering a noninvasive method for early AKI-related brain injury detection.
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01:22Acute Kidney Injury I: Introduction