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• Original Article •
Dynamic DTI assessment of white matter evolution and its correlation with neurobehavioral function after hypoxic-ischemic brain injury in neonatal rats​
MIAO Chenxu  ZHAO Xin  LI Yue  GUO Chenxi  FU Yiwei  ZHOU Tian  YANG Jinze  QIN Chi  ZHANG Xiaoan 

DOI:10.12015/issn.1674-8034.2026.02.018.


[Abstract] Objective To longitudinally and dynamically assess the temporal patterns of white matter evolution after hypoxic-ischemic (HI) injury in neonatal rats using diffusion tensor imaging (DTI), and to explore its correlation with both short-term and long-term neurobehavioral outcomes.Materials and Methods A total of twenty-six 7-day-old Sprague-Dawley (SD) rats were randomly assigned to either a sham operation group (Sham) or a HI group, with 13 rats in each group. Among them, 10 rats in each group were used for subsequent long-term in vivo magnetic resonance imaging scanning and neurobehavioral assessments, while the remaining 3 rats were sacrificed 24 hours after HI for brain collection, to be used for Western blot (WB) and quantitative real-time polymerase chain reaction (qRT-PCR). The HI model was established using the modified Rice-Vannucci method. The Sham group underwent identical surgical procedures except for common carotid artery ligation and hypoxia. Post-modeling, body weight was monitored daily for 7 days, and brain infarction volume was assessed via T2-weighted imaging (T2WI) at 24 hours post-HI. DTI scans were performed on days 1, 3, and 7 post-HI, and fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured in the cerebral cortex, hippocampus, and corpus callosum. The expression levels of IL-1β and TNF-α were detected by WB and qRT-PCR. Neurobehavioral assessments were conducted from post-operative day 1 to day 30, with short-term evaluations including the negative geotaxis test and the 28-point neuroscore, and long-term evaluations comprising the rotarod test, open field test, Y-maze, and novel object recognition test.Results Compared to the Sham group, the HI group exhibited a reduced body weight gain rate within 7 days post-HI (P < 0.05), increased cerebral infarction volume at 24 hours post-HI, and up-regulated expression of the inflammatory factors IL-1β and TNF-α in brain tissue (P < 0.001). The HI group showed a progressive decrease in FA values and an increase in MD, AD, and RD values across the three brain regions starting from post-HI day 1. Behaviorally, the HI group demonstrated prolonged negative geotaxis latency, shortened rotarod fall latency, reduced percentage of time spent in the center of the open field, decreased discrimination index in the novel object recognition test, and lowered spontaneous alternation rate in the Y-maze (all P < 0.001). Regarding the regional differences in the association, FA values in the cerebral cortex were closely associated with motor function (e.g., positively correlated with rotarod performance, r = 0.82, P < 0.001), while hippocampal FA values were highly correlated with cognitive performance (e.g., positively correlated with Y-maze performance, r = 0.77, P < 0.001). In terms of temporal evolution, the correlation between white matter metrics and short-term behavioral performance strengthened from day 1 to day 7. DTI parameters on day 7 versus long-term behaviors indicated that FA values in multiple brain regions were positively correlated with rotarod performance, the 28-point neuroscore, open field activity, Y-maze performance, and novel object recognition, whereas MD, AD, and RD values showed negative correlations.Conclusions It was found that HI injury in neonatal rats induced progressive white matter damage accompanied by neuroinflammation, which was most severe on day 7, correlated closely with neurobehavioral deficits. Moreover, this association exhibited distinct region-dependent differences, characterized by motor deficits being primarily linked to white matter injury in the cerebral cortex, whereas cognitive impairments were more closely associated with hippocampal damage. Therefore, early DTI parameters hold promise as potential imaging biomarkers for assessing injury severity and predicting long-term neurological outcomes, providing a critical time window and theoretical foundation for early clinical intervention.
[Keywords] hypoxic-ischemic brain injury；neonatal rat；diffusion tensor imaging；magnetic resonance imaging；white matter injury；neurobehavior

MIAO Chenxu1, 2, 3   ZHAO Xin1, 2, 3   LI Yue1, 2, 3   GUO Chenxi1, 2, 3   FU Yiwei1, 2, 3   ZHOU Tian1, 2, 3   YANG Jinze1, 2, 3   QIN Chi1, 2, 3   ZHANG Xiaoan1, 2, 3*  

1 Department of Medical Imaging, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China

2 Henan International Joint Laboratory of Neuromedical Imaging, Zhengzhou 450052, China

3 Henan Provincial Key Laboratory of Pediatric Neuroimaging Medicine, Zhengzhou 450052, China

Corresponding author: ZHANG X A, E-mail: zxa@zzu.edu.cn

Conflicts of interest   None.

Received  2025-11-03
Accepted  2026-01-05
DOI: 10.12015/issn.1674-8034.2026.02.018
DOI:10.12015/issn.1674-8034.2026.02.018.

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