title: Neuroplasticity for spontaneous functional recovery after neonatal hypoxic ischemic brain injury in rats observed by functional MRI and diffusion tensor imaging.
abstract: For infants and children, an incredible resilience from injury is often observed. There is growing evidence that functional recovery after brain injury might well be a consequence of the reorganization of the neural network as a process of neuroplasticity. We demonstrate the presence of neuroplasticity at work in spontaneous recovery after neonatal hypoxic ischemic (HI) injury, by elucidating a precise picture in which such reorganization takes place using functional MRI techniques. For all 12 siblings, 6 rats were subjected to severe HI brain injury and 6 rats underwent sham operation only. Severe HI brain injury was induced to postnatal day 7 (p7) Sprague-Dawley rats according to the Rice-Vannucci model (right carotid artery occlusion followed by 150min of hypoxia with 8% O2 and 92% of N2). Brain activation maps along with anatomical and functional connectivity maps related to the sensory motor function were obtained at adult (p63) using blood oxygen level dependent (BOLD)-functional MRI (fMRI), resting state-functional MRI (rs-fMRI) and diffusion tensor imaging (DTI); each of these MRI data was related to sensory motor functional outcome. In-depth investigation of the functional MRI data revealed: 1) intra-hemispheric expansion of BOLD signal activation in the contralesional undamaged hemisphere for ipsilesional forepaw stimuli to include the M2 and Cg1 in addition to the S1 and M1 wide spreading in the anterior and posterior directions, 2) inter-hemispheric transfer of BOLD signal activation for contralesional forepaw stimuli, normally routed to the injured hemisphere, to analogous sites in the contralesional undamaged hemisphere, localized newly to the M1 and M2 with a reduced portion of the S1, 3) inter-hemispheric axonal disconnection and axonal rewiring within the undamaged hemisphere as shown through DTI, and 4) increased functional interactions within the cingulate gyrus in the HI injured rats as shown through rs-fMRI. The BOLD signal amplitudes as well as DTI and rs-fMRI data well correlate with behavioral tests (tape to remove). We found that function normally utilizing what would be the injured hemisphere is transferred to the uninjured hemisphere, and functionality of the uninjured hemisphere remains not untouched but is also rewired in an expansion corresponding to the newly formed sensorimotor function from both the contralesional and the ipsilesional sides. The conclusion drawn from the data in our current study is that enhanced motor function in the contralesional hemisphere governs both the normal and damaged sides, indicating that active plasticity with brain laterality was spontaneously generated to overcome functional loss and established autonomously through normal experience via modification of neural circuitry for neonatal HI injured brain.
authors.affiliation: Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea; Department of Global Biomedical Engineering, Sungkyunkwan University, Suwon 16419, South Korea.
authors.forename: Won-Beom
authors.initials: WB
authors.lastname: Jung
authors.affiliation: Center for Molecular and Cellular Imaging, Samsung Biomedical Research Institute, Seoul 06351, South Korea.
authors.forename: Geun Ho
authors.initials: GH
authors.lastname: Im
authors.affiliation: Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea; Samsung Advanced Institute of Health Science and Technology, Sungkyunkwan University, Seoul 06351, South Korea.
authors.forename: Julius Juhyun
authors.initials: JJ
authors.lastname: Chung
authors.affiliation: Department of Pediatrics Division of Neonatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea.
authors.forename: So-Yoon
authors.initials: SY
authors.lastname: Ahn
authors.affiliation: Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea.
authors.forename: Tae Yeon
authors.initials: TY
authors.lastname: Jeon
authors.affiliation: Samsung Advanced Institute of Health Science and Technology, Sungkyunkwan University, Seoul 06351, South Korea; Department of Pediatrics Division of Neonatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea.
authors.forename: Yun Sil
authors.initials: YS
authors.lastname: Chang
authors.affiliation: Department of Pediatrics Division of Neonatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea.
authors.forename: Won Soon
authors.initials: WS
authors.lastname: Park
authors.affiliation: Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pediatrics Division of Neonatology, Asan Medical Center, University of Ulsan School of Medicine, Seoul 05535, South Korea.
authors.forename: Ki-Soo
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea; Department of Global Biomedical Engineering, Sungkyunkwan University, Suwon 16419, South Korea; Samsung Advanced Institute of Health Science and Technology, Sungkyunkwan University, Seoul 06351, South Korea. Electronic address: hijunghee@skku.edu.
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000503:physiopathology*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D004195:Disease Models, Animal; D059907:Functional Neuroimaging / Q000379:methods*; D020925:Hypoxia-Ischemia, Brain / Q000503:physiopathology*; D009043:Motor Activity / Q000502:physiology*; D009044:Motor Cortex / Q000503:physiopathology*; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D013003:Somatosensory Cortex / Q000503:physiopathology*
keywords: DTI; Developing brain; Hypoxic–ischemic brain; Plasticity; Resting state-fMRI; fMRI