Hypoxic ischemic (HI) insult damages premature white matter and grey matter in infants and causes significant mortality and morbidity. To investigate the pathological mechanisms of neonatal HI injury and find satisfactory treatments, animal models of neonatal hypoxic ischemic injury have been established and widely used. In this project, novel in vivo magnetic resonance imaging and computational techniques will be used to examine the spatiotemporal evolution of HI injury in a neonatal mouse model. Longitudinal multi-contrast MRI data will be collected and analyzed with co-registered end-point histological data in a common framework based on our MR based atlas of the developing mouse brain.
In aim 1, we will examine grey and white matter injury using in vivo MRI/histology combined analysis.
In aim 2, we will examine neurodegeneration in the cortex, hippocampus, and cerebellum using oscillating gradient diffusion MRI and histology.
In aim3, we will integrate the longitudinal multi-contrast MRI data with histological data in the central framework to characterize the spatiotemporal progression of neonatal HI injury and its regional specificity. We will then use the tools developed here to characterize HI injury in mice lacking functional Fas death receptor. We will also examine the neuroprotective effects of necrostatin in this model. We expect the project to provide detailed maps of temporal course of injury and regional susceptibility, extend our knowledge on the relationships between pathology and diagnostic markers in the mouse model, and shed light on the mechanisms of HI injury and potential treatments. This information and techniques developed in this project will be useful to design effective strategies for intervention and to monitor treatment response in studies using this or similar models.
Neonatal hypoxic ischemic (HI) injury causes significant mortality and morbidity. To find satisfactory treatment, we will examine the complex spatiotemporal patterns of neonatal HI injury in a well-established mouse model using in vivo longitudinal multi-contrast magnetic resonance imaging data and histology.
|Kakkad, Samata; Zhang, Jiangyang; Akhbardeh, Alireza et al. (2016) Collagen fibers mediate MRI-detected water diffusion and anisotropy in breast cancers. Neoplasia 18:585-593|
|Chavez-Valdez, Raul; Flock, Debbie L; Martin, Lee J et al. (2016) Endoplasmic reticulum pathology and stress response in neurons precede programmed necrosis after neonatal hypoxia-ischemia. Int J Dev Neurosci 48:58-70|
|Xu, Jiadi; Qin, Qin; Wu, Dan et al. (2016) Steady pulsed imaging and labeling scheme for noninvasive perfusion imaging. Magn Reson Med 75:238-48|
|Peng, Qi; Wu, Bin; Jiang, Mali et al. (2016) Characterization of Behavioral, Neuropathological, Brain Metabolic and Key Molecular Changes in zQ175 Knock-In Mouse Model of Huntington's Disease. PLoS One 11:e0148839|
|Wu, Dan; Zhang, Jiangyang (2016) In vivo mapping of macroscopic neuronal projections in the mouse hippocampus using high-resolution diffusion MRI. Neuroimage 125:84-93|
|Breu, Markus; Zhang, Jiangyang; Porambo, Michael et al. (2016) Diffusion Tensor Imaging Abnormalities in the Cerebral White Matter Correlate with Sex-Dependent Neurobehavioral Deficits in Adult Mice with Neonatal Ischemia. Dev Neurosci 38:83-95|
|Wu, Dan; Zhang, Jiangyang (2016) Recent Progress in Magnetic Resonance Imaging of the Embryonic and Neonatal Mouse Brain. Front Neuroanat 10:18|
|Wu, Dan; Zhang, Jiangyang (2016) The Effect of Microcirculatory Flow on Oscillating Gradient Diffusion MRI and Diffusion Encoding with Dual-Frequency Orthogonal Gradients (DEFOG). Magn Reson Med :|
|Burnsed, Jennifer C; Chavez-Valdez, Raul; Hossain, Mir Shanaz et al. (2015) Hypoxia-ischemia and therapeutic hypothermia in the neonatal mouse brain--a longitudinal study. PLoS One 10:e0118889|
|Schunke, Kathryn J; Toung, Thomas K; Zhang, Jian et al. (2015) A novel atherothrombotic model of ischemic stroke induced by injection of collagen into the cerebral vasculature. J Neurosci Methods 239:65-74|
Showing the most recent 10 out of 18 publications