Hypercapnia-induced modifications of neuronal function in the cerebral cortex of newborn piglets.
There is significant controversy over the effects of hypercapnia on the human newborn brain. Previous studies have shown that 1 h of an arterial CO2 pressure (Paco2) of 80 mm Hg alters brain cell membrane Na+K+-ATPase enzyme activity in the cerebral cortex of newborn piglets. The present study tests the hypothesis that hypercapnia (either a Paco2 of 65 or 80 mm Hg) results in decreased energy metabolism and alters neuronal nuclear enzyme activity and protein expression, specifically Ca++/calmodulin-dependent kinase (CaMK) IV activity, phosphorylation of cAMP response element binding protein (CREB), and expression of apoptotic proteins in cortical neuronal nuclei of newborn piglets. Studies were performed in 20 anesthetized normoxic piglets ventilated at either a Paco2 of 65 mm Hg, 80 mm Hg, or 40 mm Hg for 6 h. Energy metabolism was documented by ATP and phosphocreatine (PCr) levels. Results show ATP and PCr levels were significantly lower in the hypercapnic groups than the normocapnic. CaMK IV activity, phosphorylated CREB density, and Bax protein expression were all significantly higher in the hypercapnic groups than the normocapnic group. Bcl-2 protein was similar in all three groups, making the ratio of Bax/Bcl-2 significantly higher in the hypercapnic groups than in the normocapnic group. We conclude that hypercapnia alters neuronal energy metabolism, increases phosphorylation of transcription factors, and increases the expression of apoptotic proteins in the cerebral cortex of newborn piglets and therefore may be deleterious to the newborn brain.
Fritz
Karen I
KI
Department of Pediatrics, Drexel University College of Medicine and St. Christopher's Hospital for Children, Division of Neonatology, Front and Erie Sts., Ste. 2212, Philadelphia, PA 19134, USA. Karen.I.Fritz@Drexel.edu
Zubrow
Alan
A
Mishra
Om P
OP
Delivoria-Papadopoulos
Maria
M
D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D002245:Carbon Dioxide / Q000737:chemistry; D002352:Carrier Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D010766:Phosphorylation; D011312:Pressure; D011494:Protein Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013552:Swine; D013997:Time Factors; D051028:bcl-2-Associated X Protein
D002352:Carrier Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D010725:Phosphocreatine; D002245:Carbon Dioxide; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D011494:Protein Kinases; C517683:CAMK4 protein, human; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium