title: 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.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hae-Jeong
authors.initials: HJ
authors.lastname: Park
authors.forename: Chul Hoon
authors.initials: CH
authors.lastname: Kim
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Park
authors.forename: Bumhee
authors.initials: B
authors.lastname: Park
authors.forename: So Ra
authors.initials: SR
authors.lastname: Oh
authors.forename: Maeng-Keun
authors.initials: MK
authors.lastname: Oh
authors.forename: Chang Il
authors.initials: CI
authors.lastname: Park
authors.forename: Jong Doo
authors.initials: JD
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000818:Animals; D002547:Cerebral Palsy / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D002648:Child; D005260:Female; D005442:Flumazenil / Q000031:analogs & derivatives*; D005786:Gene Expression Regulation; D006429:Hemiplegia / Q000150:complications*; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D009044:Motor Cortex / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D049268:Positron-Emission Tomography; D011485:Protein Binding; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D055815:Young Adult
chemical_list: C483765:2'-fluoroflumazenil; D011963:Receptors, GABA-A; D005442:Flumazenil
keywords: GABA-A receptor; cerebral palsy; connectivity; hemiplegic spastic cerebral palsy