Brain Advance Access published online on July 9, 2008
Brain, doi:10.1093/brain/awn139
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1H/13C MR spectroscopic imaging of regionally specific metabolic alterations after experimental stroke
1Department of Medical Imaging, Image Sciences Institute, 2Department of Neurosurgery, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands and 3Department of Diagnostic Radiology, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, CT, USA
Correspondence to:
Rick M. Dijkhuizen, Image Sciences Institute, University Medical Center Utrecht, Yalelaan 2, 3584 CM, Utrecht, the Netherlands E-mail: rick{at}invivonmr.uu.nl
Loss of function and subsequent spontaneous recovery after ischaemic stroke are associated with functional and structural alterations in brain tissue. Acute functional tissue damage involves distortion of key metabolic processes, such as oxidative glycolysis and neurotransmitter metabolism. Nevertheless, initially perturbed metabolism may be restored at later stages, e.g. in perilesional areas, which could play a key role in post-stroke recovery of brain function. The pattern of metabolic recovery in relation to ischaemic tissue damage, however, is basically unknown. The goal of our study was to reveal changes in glycolysis and glutamatergic neurotransmitter metabolism that could underlie post-stroke changes in functional status. We performed in vivo 1H/13C magnetic resonance spectroscopic imaging (MRSI) during 13C-labelled glucose infusion, and MRI, at 24 h (n = 6) and 3 weeks (n = 8) after stroke in a rat model to characterize alterations in baseline metabolite levels, glutamate (Glu) and glutamine (Gln) turnover, and active lactate (Lac) formation in areas with different degrees of ischaemic injury. Inside the lesion, we detected significant reductions in baseline metabolite levels, ongoing Lac formation and seriously diminished Glu and Gln turnover at both time points, indicative of irreversible functional tissue damage. In perilesional areas, significant decrease of N-acetyl aspartate (NAA) levels, and Glu and Gln turnover indicated neuronal dysfunction at 24 h. After 3 weeks, when animals showed significant neurological improvement, anaerobic glycolysis had ceased, NAA levels were normalized, Glu turnover was maintained and Gln turnover had recovered. These findings point out that early metabolic impairment in the lesion borderzone can be restored over time. Alterations in brain metabolism in perilesional areas probably contribute significantly to changes in functional status in stroke subjects, and may provide a gateway for therapeutic strategies directed at improvement of functional recovery after stroke.
Key Words: brain metabolism; brain plasticity; magnetic resonance spectroscopy; neurotransmission; stroke
Abbreviations: MRSI, magnetic resonance spectroscopic imaging; Glu, glutamate; Gln = glutamine; Lac = lactate; NAA, N-acetyl aspartate; MCA, middle cerebral artery; EPI, echo planar imaging; TR, repetition time; TE = echo time; CBV, cerebral blood volume; FE, fractional enrichment; VOI = volume-of-interest; IL = ipsilateral; CL = contralateral; Lip = lipids; Cho = choline; Ins = myo-inositol; Tau = taurine
Received January 29, 2008. Revised June 5, 2008. Accepted June 9, 2008.