Abstract

The objective of this proposal is to examine the mechanisms by which perinatal HI causes long-term neurological functional alterations by focusing on the glutamatergic and NOS systems. Cerebellar granule cell cultures and brain slices prepared from rat pups, which have experienced neonatal HI, will first be used to examine whether neonatal HI has similar long-term effects on glutamate receptor and the NO system as intrauterine HI has, using excitatory amino acid-stimulated cyclic guanosine monophosphate formation and phosphoinositide hydrolysis, and NOS activity as parameters. Time course studies of protein expression of NMDA receptor subunits, subtypes of the metabotropic glutamate receptor, as well as NOS isoforms will be performed after intrauterine and neonatal HI, using Western blot and immunocytochemical staining. Expression of mRNA coding for these proteins will also be examined, using Northern blot and reverse transcriptase-polymerase chain reaction. Post-treatment with NOS inhibitor will be used in the neonatal HI model to examine whether it is effective in both reducing HI-induced brain injury and reversing HI-induced alterations in the expression of NOS and glutamate receptors.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HD035496-02
Application #
2674114
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1997-07-01
Project End
2002-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of Mississippi Medical Center
Department
Pediatrics
Type
Schools of Medicine
DUNS #
928824473
City
Jackson
State
MS
Country
United States
Zip Code
39216

  Publications

Lan, Kuo-Mao; Tien, Lu-Tai; Cai, Zhengwei et al. (2016) Erythropoietin Ameliorates Neonatal Hypoxia-Ischemia-Induced Neurobehavioral Deficits, Neuroinflammation, and Hippocampal Injury in the Juvenile Rat. Int J Mol Sci 17:289
Fan, Lir-Wan; Tien, Lu-Tai; Zheng, Baoying et al. (2011) Dopaminergic neuronal injury in the adult rat brain following neonatal exposure to lipopolysaccharide and the silent neurotoxicity. Brain Behav Immun 25:286-97
Wang, Kuo-Ching; Wang, Su-Jane; Fan, Lir-Wan et al. (2011) Interleukin-1 receptor antagonist ameliorates neonatal lipopolysaccharide-induced long-lasting hyperalgesia in the adult rats. Toxicology 279:123-9
Fan, Lir-Wan; Tien, Lu-Tai; Lin, Rick C S et al. (2011) Neonatal exposure to lipopolysaccharide enhances vulnerability of nigrostriatal dopaminergic neurons to rotenone neurotoxicity in later life. Neurobiol Dis 44:304-16
Simpson, Kimberly L; Weaver, Kristin J; de Villers-Sidani, Etienne et al. (2011) Perinatal antidepressant exposure alters cortical network function in rodents. Proc Natl Acad Sci U S A 108:18465-70
Fan, L W; Tien, L T; Zheng, B et al. (2010) Interleukin-1beta-induced brain injury and neurobehavioral dysfunctions in juvenile rats can be attenuated by alpha-phenyl-n-tert-butyl-nitrone. Neuroscience 168:240-52
Pang, Y; Campbell, L; Zheng, B et al. (2010) Lipopolysaccharide-activated microglia induce death of oligodendrocyte progenitor cells and impede their development. Neuroscience 166:464-75
Pang, Yi; Zheng, Baoying; Campbell, Leigh R et al. (2010) IGF-1 can either protect against or increase LPS-induced damage in the developing rat brain. Pediatr Res 67:579-84
Fan, Lir-Wan; Mitchell, Helen J; Tien, Lu-Tai et al. (2009) Interleukin-1beta-induced brain injury in the neonatal rat can be ameliorated by alpha-phenyl-n-tert-butyl-nitrone. Exp Neurol 220:143-53
Lin, Shuying; Fan, Lir-Wan; Rhodes, Philip G et al. (2009) Intranasal administration of IGF-1 attenuates hypoxic-ischemic brain injury in neonatal rats. Exp Neurol 217:361-70

Showing the most recent 10 out of 11 publications