Application of diceCT to Study the Development of the Zika Virus-Infected Mouse Brain
Abstract
:1. Introduction
2. Materials and Methods
2.1. ZIKV Stocks and Infection of Neonatal Mice
2.2. DiceCT Staining and Scanning
2.3. Image Segmentation, Visualisation, and Quantitation of Brain Volumes
2.4. Blinded Review of 6 dpi Scans
2.5. Tissue Destaining and Preparation of Sections
2.6. Immunolabelling and Nissl Staining of Post-diceCT Tissue
2.7. Statistical Analyses
3. Results
3.1. DiceCT Can Track Brain Development and the Impact of ZIKV Infection
3.2. Tissue Can Be Utilised Post diceCT for Traditional Histology and Immunostaining
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Mouse ID | Weight (g) | Head Length, L, Width, W, Depth, D (cm) | ZIKV RT-PCR | Movement |
1 | 6.40 | L = 1.9; W = 0.8; D = 0.6 | positive | Mild hind limb dysfunction |
2 | 7.50 | L = 2.3; W = 1; D = 1 | negative | normal |
3 | 6.64 | L = 2.1; W = 1.2; D = 0.9 | positive | Mild hind limb dysfunction |
4 | 5.93 | L = 2.1; W = 0.9; D = 0.7 | positive | Mild hind limb dysfunction |
5 | 7.37 | L = 1.8; W = 0.7; D = 0.8 | negative | normal |
6 | 7.34 | L = 2.1; W = 0.9; D = 0.7 | negative | normal |
Mean ± SEM | Body Weight (g) | Head Length (cm) | Head Width (cm) | Head Depth (cm) |
Mock (2, 5, 6) | 7.40 ± 0.05 | 2.17 ± 0.07 | 1.03 ± 0.09 | 0.87 ± 0.09 |
ZIKV (1, 3, 4) | * 6.32 ± 0.21 | 1.93 ± 0.09 | 0.8 ± 0.06 | 0.7 ± 0.06 |
p = 0.007, t = 5.042, df = 4 | p = 0.102, t = 2.211, df = 4 | p = 0.091, t = 2.214, df = 4 | p = 0.189, t = 1.581, df = 4 |
Mouse ID | Reviewer 1 | Reviewer 2 | Reviewer 3 | Reviewer 4 |
---|---|---|---|---|
1 | No pathological findings were noted | No pathological findings were noted | No pathological findings were noted | No pathological findings were noted |
UI | UI | UI | UI | |
2 | Major gap at the rear of the brain | Asymmetrical gaps at the level of the hippocampus/thalamus | Asymmetrical, apparent volume loss in the hippocampus | Asymmetrical, increased space between the hippocampal region and thalamus and towards the hindbrain |
ZIKV | ZIKV | ZIKV | ZIKV | |
3 | No pathological findings were noted | Some gaps, but no asymmetrical volume loss | No pathological findings were noted | Slight gaps between the hippocampal region and thalamus |
probably UI | UI | UI | probably UI | |
4 | Multiple asymmetrical gaps penetrating across the midbrain | Clear asymmetrical gaps between structures, with the majority of abnormalities around the thalamus and hippocampus, continuing through the posterior brain | Very clear asymmetrical abnormalities, particularly at the level of the posterior hippocampus, and continuing more posteriorly | Gaps between hippocampus and cortex (right) and thalamus (left); Gap (right) appears to go through the majority of the brain |
ZIKV | ZIKV | ZIKV | ZIKV | |
5 | Maybe minor anomalies; | Asymmetrical gaps between the hippocampus and thalamus | Abnormality in the region anterior to nuc accumbens and at the level of striatum (less defined); Clear asymmetry at the level of the poster hippocampus; | Gap between the hippocampal region and the thalamus |
UD | ZIKV | ZIKV | probably ZIKV | |
6 | Symmetrical gaps penetrating across images through the midbrain | Clear gaps at the hippocampus, continuing throughout the posterior brain | Very clear abnormalities, particularly at the level of the posterior hippocampus and extending posteriorly | Gap between the hippocampal region and thalamus on the left and right side, which runs through the majority of the brain |
ZIKV | ZIKV | ZIKV | ZIKV | |
7 | Maybe minor anomalies | Minor abnormalities | Some minor abnormality, which may be an imaging artifact or normal anatomical variation | Slight gap between the hippocampal region and thalamus; |
UD | UI | UD | probably UI |
Mouse Number | Total Brain | 1. Olfactory Bulb | 2. Cerebrum | 3. Hippocampus | 4. Interbrain | 5. Midbrain | 6. Cerebellum | 7. Hindbrain |
---|---|---|---|---|---|---|---|---|
1 | 14,940 | 974 | 6985 | 878 | 1922 | 1221 | 1437 | 1522 |
2 | 15,549 | 786 | 8429 | 549 | 1408 | 1486 | 1378 | 1513 |
3 | 15,534 | 787 | 8665 | 726 | 1377 | 1174 | 1385 | 1421 |
4 | 15,677 | 775 | 8604 | 892 | 1312 | 1210 | 1353 | 1531 |
5 | 15,565 | 774 | 7845 | 974 | 1794 | 1126 | 1406 | 1646 |
6 | 16,045 | 822 | 8412 | 861 | 1699 | 1347 | 1489 | 1416 |
7 | 15,402 | 718 | 8397 | 623 | 1569 | 1198 | 1490 | 1407 |
SD | 305 | 75 | 550 | 145 | 214 | 114 | 50 | 80 |
mean | 15,530 | 805 | 8191 | 786 | 1583 | 1252 | 1420 | 1494 |
% variation from the mean | 1.9 | 9.3 | 6.7 | 18.4 | 13.5 | 9.1 | 3.5 | 5.3 |
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Green, A.L.; Cowell, E.C.; Carr, L.M.; Hemsley, K.; Sherratt, E.; Collins-Praino, L.E.; Carr, J.M. Application of diceCT to Study the Development of the Zika Virus-Infected Mouse Brain. Viruses 2024, 16, 1330. https://doi.org/10.3390/v16081330
Green AL, Cowell EC, Carr LM, Hemsley K, Sherratt E, Collins-Praino LE, Carr JM. Application of diceCT to Study the Development of the Zika Virus-Infected Mouse Brain. Viruses. 2024; 16(8):1330. https://doi.org/10.3390/v16081330
Chicago/Turabian StyleGreen, Amy L., Evangeline C. Cowell, Laura M. Carr, Kim Hemsley, Emma Sherratt, Lyndsey E. Collins-Praino, and Jillian M. Carr. 2024. "Application of diceCT to Study the Development of the Zika Virus-Infected Mouse Brain" Viruses 16, no. 8: 1330. https://doi.org/10.3390/v16081330