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R Mulkern

Publications and source records attributed to R Mulkern.

5 recordsLinked to original sources
PubMed1999

In vivo development of brain phosphocreatine in normal and creatine-treated rabbit pups.

To study the effects of creatine (Cr) on brain energy metabolism and on hypoxia-induced seizures, 5- to 30-day-old rabbit pups were given subcutaneous Cr (3 g/kg) for 3 days before exposure to 4% O2 for 8 min. In saline-treated controls, hypoxic seizures were most frequent at 15 days (80% of pups) and 20 days (60%) of age. Seizures were prevented at 15 days and reduced 60% at 20 days in Cr-treated pups. In surface coil-localized brain 31P nuclear magnetic resonance spectra, with signal from both cerebral gray (GM) and white (WM) matter, the phosphocreatine (PCr)/nucleoside triphosphate (NTP) ratio doubled between 5 and 30 days of age in controls. In all Cr-injected pups, brain PCr/NTP increased to values seen in 30-day-old controls. When spectra were acquired in predominantly GM and WM slices in vivo, the PCr/NTP ratio was very low in GM at 5 days but reached adult levels by 15 days in controls. In WM, the ratio increased steadily from 5 to 30 days of age. In Cr-injected pups, PCr/NTP increased to mature levels in WM and in GM at all ages. In conclusion, hypoxic seizures occur midway in the time course of brain PCr/NTP increase in rabbit pups as previously described in rat pups. In both altricial pups, systemic Cr increases brain PCr/NTP ratio and prevents hypoxic seizures. These results suggest that mature levels of PCr and/or Cr in brain limit EEG activation either directly or indirectly by preventing hypoxic metabolic changes.

Adenosine Triphosphate↗
PubMed1998

In vivo phosphocreatine and ATP in piglet cerebral gray and white matter during seizures.

The creatine kinase (CK) reaction is thought to be important in coupling ATP metabolism and regulating ADP concentration in tissues with high and variable ATP turnover, including cerebral gray matter (GM). There is low phosphocreatine (PCr), low CK reaction rates, and high mitochondrial CK (MiCK) isoenzyme activity in GM compared to white matter (WM). To compare the CK reaction in GM and WM when ATP metabolism is high, CK reactants and reaction rates were measured in predominantly GM and WM slices in vivo in 2 and 14-day old piglets during pentylenetetrazole (PTZ) seizures using 31P nuclear magnetic resonance (NMR) 1-dimensional chemical shift imaging (CSI). Arterial pressure, temperature, and blood gasses were stable at both ages. Before seizures, the PCr/nucleoside triphosphate (NTP) ratio was higher in WM than GM at both ages with a developmental increase seen in WM. The CK reaction rate constant increased in both regions between 2 and 14 days. During seizures, PCr/NTP increased in GM at 14 days due to increased PCr while the ratio and PCr decreased in WM. The NTP was more stable in WM and GM at both ages. The CK reaction rate decreased in both regions more at 2 than at 14 days. Thus, brain ATP, deduced from NTP, is stable during seizures in the piglet. In GM stable ATP is associated with a unique increase in PCR concentration.

Adenosine Triphosphate↗
PubMed1996

Phosphocreatine and creatine kinase in piglet cerebral gray and white matter in situ.

Rates of adenosine triphosphate (ATP) metabolism are higher in cerebral gray matter than in white matter. Like other excitable tissues, brain contains a phosphocreatine (PCr)/creatine kinase (CK)/ATP system including cytosolic (B-CK) and mitochondrial (Mi-CK) isozymes. High B-CK activity is present in white and gray matter while Mi-CK is mostly in gray matter. An in situ localizing 31P-NMR technique, one-dimensional chemical shift imaging (1D-CSI), has been used to study the PCr/CK/ATP system in these regions. In the metabolically mature 4-week-old piglet, the PCr/nucleoside triphosphate (NTP) ratio measured by the 1D-CSI technique is at least 50% higher in white than gray matter. Total creatine (Cr), ATP, and total NTP concentrations are the same in rapidly frozen rat white and gray matter, suggesting that PCr/Cr ratio is much higher in white matter. The PCr increases more in gray than white matter between 4 days and 4 weeks of age in piglet brain. The CK catalyzed reaction rate constant, measured by combining the saturation transfer experiment with the 1D-CSI, is also much higher in white than gray matter at both ages. The postnatal maturational increase in the CK rate constant is greater in gray matter. In summary, these differences in PCr concentration and CK reaction rates and isozymes characterize two physiologically different PCr/CK/ATP systems in gray and white matter.

Animals↗