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. 2015 Nov;35(11):1852-61.
doi: 10.1038/jcbfm.2015.143. Epub 2015 Jun 24.

The Effects of Perturbed Cerebral Blood Flow and Cerebrovascular Reactivity on Structural MRI and Behavioral Readouts in Mild Traumatic Brain Injury

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Free PMC article

The Effects of Perturbed Cerebral Blood Flow and Cerebrovascular Reactivity on Structural MRI and Behavioral Readouts in Mild Traumatic Brain Injury

Justin A Long et al. J Cereb Blood Flow Metab. .
Free PMC article

Abstract

This study investigated the effects of perturbed cerebral blood flow (CBF) and cerebrovascular reactivity (CR) on relaxation time constant (T2), apparent diffusion coefficient (ADC), fractional anisotropy (FA), and behavioral scores at 1 and 3 hours, 2, 7, and 14 days after traumatic brain injury (TBI) in rats. Open-skull TBI was induced over the left primary forelimb somatosensory cortex (N=8 and 3 sham). We found the abnormal areas of CBF and CR on days 0 and 2 were larger than those of the T2, ADC, and FA abnormalities. In the impact core, CBF was reduced on day 0, increased to 2.5 times of normal on day 2, and returned toward normal by day 14, whereas in the tissue surrounding the impact, hypoperfusion was observed on days 0 and 2. CR in the impact core was negative, most severe on day 2 but gradually returned toward normal. T2, ADC, and FA abnormalities in the impact core were detected on day 0, peaked on day 2, and pseudonormalized by day 14. Lesion volumes peaked on day 2 and were temporally correlated with forelimb asymmetry and foot-fault scores. This study quantified the effects of perturbed CBF and CR on structural magnetic resonance imaging and behavioral readouts.

Figures

Figure 1
Figure 1
Representative cerebral blood flow, T2, apparent diffusion coefficient, apparent diffusion coefficient, and CO2 reactivity maps at 1 hour, 3 hours, and 2, 7, and 14 days post traumatic brain injury. Gray-scale Bar for cerebral blood flow: −1 to 2.5 mL/g/min, T2: 30 to 100 ms, apparent diffusion coefficient: 0.0004–0.0013 mm2/s, fractional anisotropy: 0.1–0.6; color scale bar for CO2 reactivity: −100% (blue-purple) to 100% (red-yellow).
Figure 2
Figure 2
Normalized (A) cerebral blood flow, (B) T2, (C) apparent diffusion coefficient, and (D) fractional anisotropy from the ipsilesional cortex at different time points after traumatic brain injury. Values were normalized to homologous region in the contralesional cortex (mean±s.e.m., n=8, * P<0.05, ** P<0.01, *** P<0.001 between ipsilesional and contralesional sides). Cerebral blood flow, T2, apparent diffusion coefficient, and fractional anisotropy of the homologous region in the contralesional cortex did not change with time and were not statistically different from sham-operated animals.
Figure 3
Figure 3
Line graphs of the temporal progression of % cerebral blood flow changes responding to 5% CO2 challenge in the contralesional and ipsilesional cortices for (A) regions of interest 1, (B) regions of interest 2, and (C) regions of interest 3 (mean±s.e.m., n=8, * P<0.05, **P<0.01, *** P<0.001 between ipsilesional and contralesional sides).
Figure 4
Figure 4
Bar graph of lesion volumes defined by T2 abnormality at 1 hour, 3  hours, 2, 7, and 14 days post traumatic brain injury (mean±s.e.m., n=8, * P<0.05, ** P<0.01, *** P<0.001). Lesion volumes were determined as pixels that had T2 values higher than the mean plus 2 s.d. of the value in the homologous contralesional region.
Figure 5
Figure 5
(A) Representative images for both Sham and traumatic brain injury animals are shown at × 20 and × 60 for DAPI (blue), glial fibrillary acidic protein (green), neurons (red) and a composite image. White arrows indicate normal neuronal soma morphology in Sham animals and abnormal morphology in traumatic brain injury animals. Gray arrows indicate glial fibrillary acidic protein positive cells in both Sham and traumatic brain injured animals. (B) Representative images for Sham and traumatic brain injury animals are shown at × 10 and × 20 for DAPI (blue) and Iba1 (green) and a composite image for each group. White arrows indicate Iba1 positive cells in the traumatic brain injury animals.
Figure 6
Figure 6
(A) Representative images for Fluro Jade staining (green) are shown at × 20 and × 60 from the cortex of sham and traumatic brain injury animals. Positive Fluro Jade cells are indicated by white arrows. (B) Histogram demonstrating the average number of Fluro Jade positive cells within the cortex in sham and traumatic brain injury animals on day 14 post traumatic brain injury.
Figure 7
Figure 7
Bar graphs of the (A) affected forelimb asymmetry and (B) affected forelimb fault scores at pre-traumatic brain injury, 2, 7, and 14 days post traumatic brain injury (mean±s.e.m., n=8, * P<0.05, ** P<0.01 between scores of Pre-traumatic brain injury and each subsequent time point).

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