An Examination of the Long-Term Neurodevelopmental Impact of Prenatal Zika Virus Infection in a Rat Model Using a High Resolution, Longitudinal MRI Approach
Since Zika virus (ZIKV) first emerged as a public health concern in 2015, our ability to identify and track the long-term neurological sequelae of prenatal Zika virus (ZIKV) infection in humans has been limited. Our lab has developed a rat model of maternal ZIKV infection with associated vertical tr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/6/1123 |
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| author | Rita T. Patel Brennan M. Gallamoza Praveen Kulkarni Morgan L. Sherer Nicole A. Haas Elise Lemanski Ibrahim Malik Khan Hekmatyar Mark S. Parcells Jaclyn M. Schwarz |
| author_facet | Rita T. Patel Brennan M. Gallamoza Praveen Kulkarni Morgan L. Sherer Nicole A. Haas Elise Lemanski Ibrahim Malik Khan Hekmatyar Mark S. Parcells Jaclyn M. Schwarz |
| author_sort | Rita T. Patel |
| collection | DOAJ |
| description | Since Zika virus (ZIKV) first emerged as a public health concern in 2015, our ability to identify and track the long-term neurological sequelae of prenatal Zika virus (ZIKV) infection in humans has been limited. Our lab has developed a rat model of maternal ZIKV infection with associated vertical transmission to the fetus that results in significant brain malformations in the neonatal offspring. Here, we use this model in conjunction with longitudinal magnetic resonance imaging (MRI) to expand our understanding of the long-term neurological consequences of prenatal ZIKV infection in order to identify characteristic neurodevelopmental changes and track them across time. We exploited both manual and automated atlas-based segmentation of MR images in order to identify long-term structural changes within the developing rat brain following inoculation. The paradigm involved scanning three cohorts of male and female rats that were prenatally inoculated with 10<sup>7</sup> PFU ZIKV, 10<sup>7</sup> UV-inactivated ZIKV (iZIKV), or diluent medium (mock), at 4 different postnatal day (P) age points: P2, P16, P24, and P60. Analysis of tracked brain structures revealed significantly altered development in both the ZIKV and iZIKV rats. Moreover, we demonstrate that prenatal ZIKV infection alters the growth of brain regions throughout the neonatal and juvenile ages. Our findings also suggest that maternal immune activation caused by inactive viral proteins may play a role in altered brain growth throughout development. For the very first time, we introduce manual and automated atlas-based segmentation of neonatal and juvenile rat brains longitudinally. Experimental results demonstrate the effectiveness of our novel approach for detecting significant changes in neurodevelopment in models of early-life infections. |
| first_indexed | 2024-03-10T10:30:28Z |
| format | Article |
| id | doaj.art-9fa60ac7eeb24e8a91699b5998b35ce9 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T10:30:28Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-9fa60ac7eeb24e8a91699b5998b35ce92023-11-21T23:40:53ZengMDPI AGViruses1999-49152021-06-01136112310.3390/v13061123An Examination of the Long-Term Neurodevelopmental Impact of Prenatal Zika Virus Infection in a Rat Model Using a High Resolution, Longitudinal MRI ApproachRita T. Patel0Brennan M. Gallamoza1Praveen Kulkarni2Morgan L. Sherer3Nicole A. Haas4Elise Lemanski5Ibrahim Malik6Khan Hekmatyar7Mark S. Parcells8Jaclyn M. Schwarz9Department of Psychological and Brain Sciences, University of Delaware, Newark, DE 19716, USADepartment of Psychological and Brain Sciences, University of Delaware, Newark, DE 19716, USACenter for Translational Neuroimaging, Department of Psychology, Northeastern University, Boston, MA 02115, USAW. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USADepartment of Psychological and Brain Sciences, University of Delaware, Newark, DE 19716, USADepartment of Psychological and Brain Sciences, University of Delaware, Newark, DE 19716, USACenter for Biomedical and Brain Imaging, Department of Psychological and Brain Sciences, University of Delaware, Newark, DE 19716, USACenter for Biomedical and Brain Imaging, Department of Psychological and Brain Sciences, University of Delaware, Newark, DE 19716, USADepartment of Animal and Food Sciences, University of Delaware, Newark, DE 19716, USADepartment of Psychological and Brain Sciences, University of Delaware, Newark, DE 19716, USASince Zika virus (ZIKV) first emerged as a public health concern in 2015, our ability to identify and track the long-term neurological sequelae of prenatal Zika virus (ZIKV) infection in humans has been limited. Our lab has developed a rat model of maternal ZIKV infection with associated vertical transmission to the fetus that results in significant brain malformations in the neonatal offspring. Here, we use this model in conjunction with longitudinal magnetic resonance imaging (MRI) to expand our understanding of the long-term neurological consequences of prenatal ZIKV infection in order to identify characteristic neurodevelopmental changes and track them across time. We exploited both manual and automated atlas-based segmentation of MR images in order to identify long-term structural changes within the developing rat brain following inoculation. The paradigm involved scanning three cohorts of male and female rats that were prenatally inoculated with 10<sup>7</sup> PFU ZIKV, 10<sup>7</sup> UV-inactivated ZIKV (iZIKV), or diluent medium (mock), at 4 different postnatal day (P) age points: P2, P16, P24, and P60. Analysis of tracked brain structures revealed significantly altered development in both the ZIKV and iZIKV rats. Moreover, we demonstrate that prenatal ZIKV infection alters the growth of brain regions throughout the neonatal and juvenile ages. Our findings also suggest that maternal immune activation caused by inactive viral proteins may play a role in altered brain growth throughout development. For the very first time, we introduce manual and automated atlas-based segmentation of neonatal and juvenile rat brains longitudinally. Experimental results demonstrate the effectiveness of our novel approach for detecting significant changes in neurodevelopment in models of early-life infections.https://www.mdpi.com/1999-4915/13/6/1123Zika virus (ZIKV)neuroimagingMRIneurodevelopmentpregnancycongenital infection |
| spellingShingle | Rita T. Patel Brennan M. Gallamoza Praveen Kulkarni Morgan L. Sherer Nicole A. Haas Elise Lemanski Ibrahim Malik Khan Hekmatyar Mark S. Parcells Jaclyn M. Schwarz An Examination of the Long-Term Neurodevelopmental Impact of Prenatal Zika Virus Infection in a Rat Model Using a High Resolution, Longitudinal MRI Approach Viruses Zika virus (ZIKV) neuroimaging MRI neurodevelopment pregnancy congenital infection |
| title | An Examination of the Long-Term Neurodevelopmental Impact of Prenatal Zika Virus Infection in a Rat Model Using a High Resolution, Longitudinal MRI Approach |
| title_full | An Examination of the Long-Term Neurodevelopmental Impact of Prenatal Zika Virus Infection in a Rat Model Using a High Resolution, Longitudinal MRI Approach |
| title_fullStr | An Examination of the Long-Term Neurodevelopmental Impact of Prenatal Zika Virus Infection in a Rat Model Using a High Resolution, Longitudinal MRI Approach |
| title_full_unstemmed | An Examination of the Long-Term Neurodevelopmental Impact of Prenatal Zika Virus Infection in a Rat Model Using a High Resolution, Longitudinal MRI Approach |
| title_short | An Examination of the Long-Term Neurodevelopmental Impact of Prenatal Zika Virus Infection in a Rat Model Using a High Resolution, Longitudinal MRI Approach |
| title_sort | examination of the long term neurodevelopmental impact of prenatal zika virus infection in a rat model using a high resolution longitudinal mri approach |
| topic | Zika virus (ZIKV) neuroimaging MRI neurodevelopment pregnancy congenital infection |
| url | https://www.mdpi.com/1999-4915/13/6/1123 |
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