cAMP response element-binding protein activation in ligation preconditioning in neonatal brain.
Perinatal hypoxic-ischemic (HI) brain injury is a major cause of permanent neurological dysfunction in children. An approach to study the treatment of neonatal HI encephalopathy that allows for neuroprotection is to investigate the states of tolerance to HI. Twenty-four-hour carotid-artery ligation preconditioning established by delaying the onset of hypoxia for 24 hours after permanent unilateral carotid ligation rats markedly diminished the cerebral injury, however, the signaling mechanisms of this carotid-artery ligation preconditioning in neonatal rats remain unknown. Ligation of the carotid artery 24 hours before hypoxia provided complete neuroprotection and produced improved performance on the Morris water maze compared with ligation performed 1 hour before hypoxia. Carotid artery ligation 6 hours before hypoxia produced intermediate benefit. The 24-hour carotid-artery ligation preconditioning was associated with a robust and sustained activation of a transcription factor, the cAMP response element-binding protein (CREB), on its phosphorylation site on Ser133. Intracerebroventricular infusions of antisense CREB oligodeoxynucleotides significantly reduced the 24-hour carotid-artery ligation-induced neuroprotection effects by decreasing CREB expressions. Pharmacological activation of the cAMP-CREB signaling with rolipram 24 hours before hypoxia protected rat pups at behavioral and pathological levels by sustained increased CREB phosphorylation. This study suggests that 24-hour carotid-artery ligation preconditioning provides important mechanisms for potential pharmacological preconditioning against neonatal HI brain injury.
Lee
Hsueh-Te
HT
Institute of Basic Medical Science, Medical College, National Cheng Kung University, Tainan, Taiwan.
Chang
Ying-Chao
YC
Wang
Lin-Yu
LY
Wang
Shan-Tair
ST
Huang
Chao-Ching
CC
Ho
Chien-Jung
CJ
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography / Q000379:methods; D001522:Behavior, Animal; D015153:Blotting, Western / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D016893:Carotid Stenosis; D002560:Cerebrovascular Circulation / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005260:Female; D005311:Fetal Hypoxia / Q000201:enzymology / Q000378:metabolism* / Q000517:prevention & control; D007839:Functional Laterality; D020925:Hypoxia-Ischemia, Brain / Q000201:enzymology / Q000378:metabolism* / Q000517:prevention & control; D007150:Immunohistochemistry / Q000379:methods; D019194:Ischemic Preconditioning / Q000379:methods*; D008026:Ligation / Q000379:methods; D008297:Male; D018782:Maze Learning / Q000502:physiology; D020319:Oligodeoxyribonucleotides, Antisense / Q000627:therapeutic use; D009929:Organ Size / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011930:Reaction Time / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D020889:Rolipram / Q000494:pharmacology; D012694:Serine / Q000378:metabolism; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D020319:Oligodeoxyribonucleotides, Antisense; D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D005576:Colforsin; D012694:Serine; D020889:Rolipram