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Mild hypoxic-ischemic injury in the neonatal rat brain: longitudinal evaluation of white matter using diffusion
1Department of Diagnostic Radiology, University of Hong Kong, Hong Kong, People's Republic of China.
Background And Purpose:
Selective white matter (WM) damage is a known sequela of mild hypoxic-ischemic (HI) injury in the neonatal rat model. The aim of this study was to evaluate longitudinally mild HI-induced WM damage (represented by the external capsule [EC]) by diffusion tensor MR imaging (DTI) and to correlate the findings with histology.
Materials And Methods:
Seven-day-old Sprague-Dawley rats (n = 19) underwent unilateral ligation of the left common carotid artery followed by hypoxia for 50 minutes to create mild HI injury. DTI was performed longitudinally at 5 time points from day 1 to day 90 postinjury (n = 19, 16, 13, 11, 9, respectively), and fractional anisotropy (FA), trace, radial diffusivity (lambda( perpendicular)), and axial diffusivity (lambda(//)) of the injury and control contralateral ECs were quantified. Rats were randomly sacrificed (n = 15, in total), and the corresponding ECs were stained with hematoxylin-eosin, Luxol fast blue (LFB), and neurofilament (NF) to evaluate morphologic changes, amount of myelin, and axonal count at every time point. A paired t test was applied to evaluate statistical differences between both ECs, and the Pearson correlation test was used to evaluate the relationships between DTI indices and histologic evaluations. In addition, longitudinal changes in DTI indices and histologic evaluations were analyzed by a linear mixed model and an analysis of variance test, respectively.
Results:
We demonstrated significantly decreased FA, increased lambda( perpendicular), and similar lambda(//) in the injury compared with the control EC, which was persistent through all time points. Histologic evaluation by LFB and NF staining showed reduced myelin stain intensity in the injury EC and similar axonal counts in both ECs. Longitudinally, there was an increase in FA, a decrease in lambda( perpendicular) and trace, and stability in lambda(//) in both ECs. Also, there was progressive reduction in the differences in FA, trace, and lambda( perpendicular) between the injury and control EC, especially between day 1 and day 7 postinjury and in tandem with changes in myelin stain. FA was significantly correlated with myelin stain (r = 0.681, P < .01) and axonal count (r = 0.673, P < .01), whereas lambda( perpendicular) was significantly correlated with myelin stain only (r = -0.528, P < .01), and lambda(//), with axonal count only (r = 0.372, P = .043).
Conclusions:
Diffusion indices can reflect dysmyelination in mild HI injury, continual myelination of both injury and control ECs with growth, and the partial recovery of myelin postinjury. We propose that diffusion indices may be used as biomarkers to monitor noninvasively the longitudinal changes of mild HI-induced WM damage.
Insights
Diffusion tensor imaging (DTI) can track white matter damage after mild hypoxic-ischemic (HI) injury in neonatal rats. DTI indices correlate with myelin and axonal changes, showing potential as biomarkers for monitoring recovery.
Area of Science:
- Neuroscience
- Radiology
- Neonatal Research
Background:
- Neonatal hypoxic-ischemic (HI) injury can cause selective white matter (WM) damage.
- The external capsule (EC) is a vulnerable WM tract in neonatal rats.
- Longitudinal assessment of HI-induced WM damage is crucial for understanding recovery.
Purpose of the Study:
- To longitudinally evaluate mild HI-induced WM damage in the EC using diffusion tensor MR imaging (DTI).
- To correlate DTI findings with histological assessments of myelin and axonal integrity.
- To explore the potential of DTI as a biomarker for monitoring WM damage.
Main Methods:
- Mild HI injury was induced in 7-day-old rats.
- DTI was performed longitudinally at 5 time points up to 90 days post-injury.
- Histological analysis (hematoxylin-eosin, Luxol fast blue, neurofilament) assessed morphologic changes, myelin, and axonal count.
Main Results:
- DTI revealed persistent decreased fractional anisotropy (FA) and increased radial diffusivity in the injured EC.
- Histology showed reduced myelin in the injured EC but similar axonal counts.
- Longitudinal DTI showed progressive recovery of FA and radial diffusivity, correlating with myelin changes.
- FA and radial diffusivity significantly correlated with myelin staining, while axial diffusivity correlated with axonal count.
Conclusions:
- Diffusion indices reflect dysmyelination and partial myelin recovery following mild HI injury.
- DTI can monitor longitudinal changes in WM damage and recovery.
- DTI indices show promise as non-invasive biomarkers for HI-induced WM injury.
