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Increased GABA-A Receptor Binding and Reduced Connectivity at the Motor Cortex in Children with Hemiplegic Cerebral Palsy: A Multimodal Investigation Using 18F-Fluoroflumazenil PET, Immunohistochemistry, and MR Imaging

Authors
 Hae-Jeong Park  ;  Chul Hoon Kim  ;  Eun Sook Park  ;  Bumhee Park  ;  So Ra Oh  ;  Maeng-Keun Oh  ;  Chang Il Park  ;  Jong Doo Lee 
Citation
 JOURNAL OF NUCLEAR MEDICINE, Vol.54(8) : 1263-1269, 2013 
Journal Title
 JOURNAL OF NUCLEAR MEDICINE 
ISSN
 0161-5505 
Issue Date
2013
MeSH
Adolescent ; Animals ; Cerebral Palsy/complications ; Cerebral Palsy/diagnostic imaging ; Cerebral Palsy/metabolism* ; Cerebral Palsy/physiopathology ; Child ; Female ; Flumazenil/analogs & derivatives* ; Gene Expression Regulation ; Hemiplegia/complications* ; Humans ; Immunohistochemistry ; Magnetic Resonance Imaging* ; Male ; Motor Cortex/diagnostic imaging ; Motor Cortex/metabolism* ; Motor Cortex/physiopathology ; Positron-Emission Tomography* ; Protein Binding ; Rats ; Receptors, GABA-A/metabolism* ; Young Adult
Keywords
GABA-A receptor ; cerebral palsy ; connectivity ; hemiplegic spastic cerebral palsy
Abstract
γ-aminobutyric acid (GABA)-A receptor-mediated neural transmission is important to promote practice-dependent plasticity after brain injury. This study investigated alterations in GABA-A receptor binding and functional and anatomic connectivity within the motor cortex in children with cerebral palsy (CP). METHODS: We conducted (18)F-fluoroflumazenil PET on children with hemiplegic CP to investigate whether in vivo GABA-A receptor binding is altered in the ipsilateral or contralateral hemisphere of the lesion site. To evaluate changes in the GABA-A receptor subunit after prenatal brain injury, we performed GABA-A receptor immunohistochemistry using rat pups with a diffuse hypoxic ischemic insult. We also performed diffusion tensor MR imaging and resting-state functional MR imaging on the same children with hemiplegic CP to investigate alterations in anatomic and functional connectivity at the motor cortex with increased GABA-A receptor binding. RESULTS: In children with hemiplegic CP, the (18)F-fluoroflumazenil binding potential was increased within the ipsilateral motor cortex. GABA-A receptors with the α1 subunit were highly expressed exclusively within cortical layers III, IV, and VI of the motor cortex in rat pups. The motor cortex with increased GABA-A receptor binding in children with hemiplegic CP had reduced thalamocortical and corticocortical connectivity, which might be linked to increased GABA-A receptor distribution in cortical layers in rats. CONCLUSION: Increased expression of the GABA-A receptor α1 subunit within the ipsilateral motor cortex may be an important adaptive mechanism after prenatal brain injury in children with CP but may be associated with improper functional connectivity after birth and have adverse effects on the development of motor plasticity.
Full Text
http://jnm.snmjournals.org/content/54/8/1263.long
DOI
10.2967/jnumed.112.117358
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Rehabilitation Medicine (재활의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Park, Bum Hee(박범희)
Park, Eun Sook(박은숙) ORCID logo https://orcid.org/0000-0002-9144-3063
Park, Chang Il(박창일)
Park, Hae Jeong(박해정) ORCID logo https://orcid.org/0000-0002-4633-0756
Oh, So Ra(오소라)
Lee, Jong Doo(이종두)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/87480
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