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Brain High Energy Phosphate Responses to Alcohol Exposure in Neonatal Rats: An In Vivo 31 P‐NMR Study
Author(s) -
Cudd Timothy A.,
Wasser Jeremy S.,
Chen WeiJung A.,
West James R.
Publication year - 2000
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2000.tb02067.x
Subject(s) - phosphocreatine , in vivo , intracellular ph , chemistry , alcohol , oxygen , oxygenation , ethanol , hypoxia (environmental) , phosphate , medicine , intracellular , endocrinology , biochemistry , biology , energy metabolism , microbiology and biotechnology , organic chemistry
Background: The mechanisms that mediate fetal brain injury which results from maternal alcohol consumption are not well understood. Although fetal hypoxia is a popularly proposed mechanism, it has been difficult to assess brain oxygenation in vivo. We measured intracellular high energy phosphate concentrations and estimated intracellular pH (pH i ) in brains of unanesthetized neonatal rat pups by using in vivo 31 P‐NMR spectroscopy. We reasoned that decreases in brain oxygenation sufficient to result in brain injury would also reduce high energy phosphates and pH i . Methods: On postnatal day 4, before alcohol administration, pups were placed into a 20 mm diameter NMR probe, their heads were positioned carefully in the center of the 31 P detection coil, and spectra were collected over 20 min. Animals were then fed diet with or without 4.5 g/kg of ethanol in two (in succession) of 12 daily feedings via artificial rearing methods. A second spectrum was collected at 90 min after the beginning of the second alcohol feeding, at the time that coincided with the peak blood alcohol concentration (BAC). Identical feedings were performed daily until day 9, when pre‐ and postfeeding spectra were again obtained. Positive control groups were fed control diet and were studied in atmospheres of 5% oxygen, 95% nitrogen or 0% oxygen, 100% nitrogen. Results: Phosphocreatine (PCr), β‐adenosine triphosphate (ATP), and pH i decreased and inorganic phosphate (P i ) increased in day 4 animals subjected to 0% oxygen (20 min) compared with pretreatment and all other treatment groups. Day 9 animals did not tolerate these conditions. There were no significant changes in response to 5% oxygen on day 4, but P i increased and β‐ATP decreased compared with pretreatment values and compared with alcohol and control groups on day 9. There were no changes in PCr, β‐ATP, or pH i in response to alcohol treatment at either age. PCr was significantly increased in the alcohol and 5% oxygen groups and apparently increased in the control group on day 9 compared with day 4, most likely due to increases in cranial muscle mass within the NMR coil. Conclusions: We conclude that acute alcohol exposure that results in peak BACs of 315 mg/dl does not alter brain high energy phosphate concentrations or pH i in neonatal rat pups, although these BACs are known to result in significant brain injury. These findings do not support hypoxia as a mechanism of alcohol‐mediated brain injury during the third trimester equivalent in the rat pup model.