Hippocampal alterations in rats of early-stage hyperuricemia using diffusion kurtosis imaging: A preliminary study

Although several quantitative methods are available for evaluating hyperuricemia-associated brain dysfunction, diffusion kurtosis imaging (DKI) exhibits greater sensitivity to subtle microstructural tissue changes, potentially enabling earlier detection of damage.

To investigate the feasibility of hyperuricemia on cognitive impairment in rats using DKI.

Fifty male rats were randomly divided into the normal control (CON) group and hyperuricemia model (HUA) group. Ten rats from each group were randomly selected and underwent longitudinal DKI scanning at baseline (week 0) and at weeks 2, 4, 6, and 8. DKI indicators were acquired with selecting bilateral symmetric regions of interest (ROI) in the hippocampal region, including, mean diffusivity (MD), fractional anisotropy (FA) and mean kurtosis (MK). The HE staining, GFAP and Iba-1 immunofluorescence staining were employed to reveal hippocampal histopathological changes. Additionally, the Morris water maze (MWM) test was applied to assess cognitive ability of rats at week 8th.

In this study, the MD and FA values of hippocampal in HUA group exhibited a gradually decreasing trend, while the MK value gradually increased. Longitudinal analysis revealed earlier MK differences (weeks 4th-8th) and later FA divergences (weeks 6th-8th) between HUA and CON groups (p < 0.05). During weeks 4th-8th, the relative fluorescence intensity (RFI) of GFAP and, Iba-1 exhibited an inverse trend with FA value, whereas their changing trend was similar to that of MK value. Compared with controls, HUA rats showed the progressively longer latencies across training days, and fewer traversals and shorter durations of the platform in spatial exploration experiments.

DKI imaging was a non-invasive and sensitive method for identifying the HUA-induced hippocampal alterations and cognitive damage.