Oral creatine supplementation has been demonstrated by several groups to increase muscle performance and mass. High concentrations of PCr and creatine are also found in the brain, which with its relatively high oxygen consumption means that, similar to muscle, brain tissue may be metabolically affected by exogenous creatine. However while there is extensive work examining how use of creatine affects muscle performance, there is relatively less work available in the brain. In this proposal we will begin to fill this gap, with non-invasive MR measurements of high energy phosphates, NAA, creatine and perfusion/oxidative metabolism in healthy controls. Furthermore, because of the increasing data that progressive metabolic dysfunction may contribute directly to the pathophysiology of epilepsy, we will also examine the metabolic and clinical effects of oral creatine supplementation in patients with temporal lobe epilepsy. This work is done in collaboration with R. Kuzniecky , MD with the NYU Comprehensive Epilepsy Center. In particular, epilepsy is known to respond to another form of """"""""metabolic therapy"""""""", the high fat ketogenic diet. As we have previously shown using MR spectroscopy, patients placed on the ketogenic diet demonstrated increases in cerebral PCr/ATP, known to be decreased in epilepsy patients. If successful, this project may show that creatine 1) can provide a supplementary avenue of therapy and 2) contribute additional evidence for a metabolic pathophysiologic component to epilepsy. ? ?

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AT002984-03
Application #
7140080
Study Section
Special Emphasis Panel (ZAT1-DB (18))
Program Officer
Khalsa, Partap Singh
Project Start
2005-08-01
Project End
2009-05-31
Budget Start
2007-06-01
Budget End
2009-05-31
Support Year
3
Fiscal Year
2007
Total Cost
$117,026
Indirect Cost
Name
Yale University
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Pan, J W; Duckrow, R B; Spencer, D D et al. (2013) Selective homonuclear polarization transfer for spectroscopic imaging of GABA at 7T. Magn Reson Med 69:310-6
Pan, Jullie W; Lo, Kai-Ming; Hetherington, Hoby P (2012) Role of very high order and degree B0 shimming for spectroscopic imaging of the human brain at 7 tesla. Magn Reson Med 68:1007-17
Pan, J W; Spencer, D D; Kuzniecky, R et al. (2012) Metabolic networks in epilepsy by MR spectroscopic imaging. Acta Neurol Scand 126:411-20
Pan, J W; Avdievich, N; Hetherington, H P (2010) J-refocused coherence transfer spectroscopic imaging at 7 T in human brain. Magn Reson Med 64:1237-46
Hetherington, Hoby P; Avdievich, Nikolai I; Kuznetsov, Andrey M et al. (2010) RF shimming for spectroscopic localization in the human brain at 7 T. Magn Reson Med 63:9-19
Zimmerman, M E; Pan, J W; Hetherington, H P et al. (2009) Hippocampal correlates of pain in healthy elderly adults: a pilot study. Neurology 73:1567-70
Avdievich, N I; Pan, J W; Baehring, J M et al. (2009) Short echo spectroscopic imaging of the human brain at 7T using transceiver arrays. Magn Reson Med 62:17-25
Pan, J W; Zaveri, H P; Spencer, D D et al. (2009) Intracranial EEG power and metabolism in human epilepsy. Epilepsy Res 87:18-24
Hetherington, Hoby (2009) Novel approaches to imaging epilepsy by MRI. Future Neurol 4:295-304
Pan, J W; Cavus, I; Kim, J et al. (2008) Hippocampal extracellular GABA correlates with metabolism in human epilepsy. Metab Brain Dis 23:457-68

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