Mild Hypoxic-Ischemic Injury in the Neonatal Rat Brain: Longitudinal Evaluation of White Matter Using Diffusion Tensor MR Imaging

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Fig 1.
Regions of interest are manually drawn over the both sides of the EC on an FA map at day 30 post-HI injury (circled area). Then, the regions of interest are placed on the identical sites on the trace, λ_//, and λ_⊥ maps.
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Fig 2.
Histologic evaluations of mild HI-induced WM damage. A and B, HE stain at day 1 post-HI injury. No necrosis area is found in the injury EC (A). Mild vacuolation changes are found in the injury EC (arrows) compared with the control EC (B). C and D, LFB stain at day 30 post-HI injury. Nerve fibers appear sparse and thinner in the injury EC (C). LFB stain shows decreased stain intensity compared with the control EC (D). E and F, NF stain at day 90 post-HI injury. Distributions and axonal counts are similar in the injury EC (E) and the control EC (F). Scale bar (in F, applicable to A-F) indicates 25 μm.

Table 1:

FA, trace, λ_//, and λ_⊥ in injury and control ECs from D1 to D90 in a mild-HI neonatal rat model*

Time Points	Injury EC	Control EC	Ratio	P
FA
D1	0.240 ± 0.051^a	0.262 ± 0.057^a	0.922 ± 0.091^a	<.01
D7	0.307 ± 0.056^b	0.321 ± 0.053^b	0.962 ± 0.132^b	<.01
D14	0.320 ± 0.040^b	0.337 ± 0.061^b	0.967 ± 0.138^b	<.01
D30	0.377 ± 0.043^c	0.392 ± 0.054^c	0.968 ± 0.147^b	<.01
D90	0.416 ± 0.037^d	0.430 ± 0.040^d	0.970 ± 0.086^b	<.01
Trace (μm²/ms)
D1	2.808 ± 0.204^a	2.683 ± 0.351^a	1.059 ± 0.121^a	<.01
D7	2.272 ± 0.019^b	2.273 ± 0.016^b	1.001 ± 0.054^b	.97
D14	2.162 ± 0.154^b	2.145 ± 0.130^b	1.008 ± 0.033^b	.08
D30	2.284 ± 0.277^b	2.260 ± 0.125^b	1.012 ± 0.053^b	.13
D90	2.272 ± 0.317^b	2.247 ± 0.303^b	1.011 ± 0.042^b	.09
λ_// (μm²/ms)
D1	1.107 ± 0.108	1.125 ± 0.107	0.987 ± 0.083	.10
D7	1.089 ± 0.109	1.091 ± 0.099	1.000 ± 0.060	.86
D14	1.082 ± 0.079	1.080 ± 0.079	1.003 ± 0.039	.73
D30	1.075 ± 0.084	1.073 ± 0.098	1.008 ± 0.113	.93
D90	1.087 ± 0.159	1.081 ± 0.157	1.009 ± 0.069	.56
λ_⊥ (μm²/ms)
D1	0.835 ± 0.083^a	0.769 ± 0.096^a	1.092 ± 0.079^a	<.01
D7	0.645 ± 0.060^b	0.616 ± 0.048^b	1.050 ± 0.100^b	<.01
D14	0.621 ± 0.061^b	0.594 ± 0.052^b	1.049 ± 0.093^b	<.01
D30	0.617 ± 0.043^b	0.591 ± 0.043^b	1.046 ± 0.073^b	<.01
D90	0.593 ± 0.076^b	0.570 ± 0.078^b	1.043 ± 0.060^b	<.01

Note:—FA indicates fractional anisotropy; EC, external capsule; λ_//, axial diffusivity; λ_⊥, radial diffusivity; Ratio, injury/control diffusion tensor imaging indices of EC; D1-D90, day 1-day 90 post HI; HI, hypoxic-ischemic.
* A paired t test was used to evaluate the statistical significance between injury and control ECs. A linear mixed model, followed by a post hoc pair-wise comparison test, was applied to evaluate significant differences among longitudinal time points. Superscript a,b,c,d,e reflect significant differences between time points. Values in the same column without a common superscript indicate a significant difference less than 0.05 between 2 time points. Values are shown as mean ± SD.

Table 2:

Histologic evaluations of mild HI-induced WM damage in injury and control ECs from D1 to D90 post-HI*

	Injury EC	Control EC	Ratio	P
LFB staining intensity (optical density)
D1	0.055 ± 0.006^a	0.081 ± 0.008^a	0.684 ± 0.086^a	<.01
D7	0.098 ± 0.008^b	0.129 ± 0.017^b	0.768 ± 0.097^b	<.01
D14	0.113 ± 0.014^c	0.143 ± 0.015^b	0.801 ± 0.160^b	<.01
D30	0.143 ± 0.015^d	0.173 ± 0.012^c	0.818 ± 0.083^b	<.01
D90	0.177 ± 0.021^e	0.214 ± 0.026^d	0.824 ± 0.092^b	<.01
Axon count
D1	201 ± 29^a	234 ± 32^a	0.859 ± 0.129	.074
D7	463 ± 48^a	503 ± 85^a	0.920 ± 0.084	.254
D14	679 ± 19	697 ± 32^a	0.974 ± 0.025	.087
D30	701 ± 132	716 ± 89^a	0.979 ± 0.084	.724
D90	1059 ± 476^b	1240 ± 402^b	0.854 ± 0.025	.335

Note:—WM indicates white matter; LFB, Luxol fast blue.
* A paired t test was used to evaluate the statistical significance between injury and control ECs. One-way analysis of variance followed by a Tukey test was used to evaluate the statistical significance among longitudinal time points. Superscript a,b,c,d,e reflect significant differences between time points. Values in the same column without a common superscript indicate a significant difference less than 0.05 between 2 time points. Values are shown as mean ± SD.