title: Learning and cognitive deficits in hypoxic neonatal rats intensified by BAX mediated apoptosis: protective role of glucose, oxygen, and epinephrine.
abstract: Hypoxic brain injury during neonatal development can lead to neuronal damage and produce learning and cognitive impairments. TOPRO-3 staining was used to visualize cell loss and real-time polymerase chain reaction (PCR) analysis of BAX mRNA was used to evaluate the level of apoptosis in the cerebral cortex, cerebellum, brain stem, and striatum of hypoxic neonatal rats and hypoxic rats resuscitated with glucose, oxygen, and epinephrine. The long-term effects of neonatal hypoxic insult on cognition and behavior were studied using Morris water maze experiment on 1-month-old rats exposed to neonatal hypoxia. In hypoxic neonatal rats, a significant cell loss (p < .001) within the brain regions was observed in TOPRO-3 staining and BAX mRNA expression was significantly upregulated (p < .001). Immediate resuscitation of hypoxic neonates with glucose, alone and along with oxygen, significantly downregulated (p < .001) BAX mRNA expression. The BAX expression in epinephrine resuscitated and 100% oxygen resuscitated groups were found to be upregulated in the brain regions. In water maze experiment, 1-month-old rats exposed to neonatal hypoxia spent lesser time in the platform quadrant (p < .001) and showed longer escape latency (p < .001) highlighting the learning and cognitive deficits. Our study revealed the effect of glucose resuscitation alone and along with oxygenation in ameliorating the spatial memory and learning deficits induced by neonatal hypoxic insult mediated brain cell loss.
authors.affiliation: Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, Kerala, India.
authors.forename: Anju Thoppil
authors.initials: AT
authors.lastname: Raveendran
authors.forename: Paulose Cheramadatikudiyil
authors.initials: PC
authors.lastname: Skaria
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000378:metabolism / Q000517:prevention & control*; D004837:Epinephrine / Q000008:administration & dosage*; D005947:Glucose / Q000008:administration & dosage*; D002534:Hypoxia, Brain / Q000378:metabolism / Q000517:prevention & control*; D007859:Learning Disabilities / Q000378:metabolism / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000008:administration & dosage; D010100:Oxygen / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D051028:bcl-2-Associated X Protein / Q000502:physiology*
chemical_list: C494828:Bax protein, rat; D018696:Neuroprotective Agents; D051028:bcl-2-Associated X Protein; D005947:Glucose; D010100:Oxygen; D004837:Epinephrine