title: 1H/13C MR spectroscopic imaging of regionally specific metabolic alterations after experimental stroke.
abstract: 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 (1)H/(13)C magnetic resonance spectroscopic imaging (MRSI) during (13)C-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.
authors.affiliation: Department of Medical Imaging, Image Sciences Institute, University Medical Center Utrecht, Yalelaan 2, 3584 CM, Utrecht, the Netherlands.
authors.forename: Jet P
authors.initials: JP
authors.lastname: van der Zijden
authors.forename: Pieter
authors.initials: P
authors.lastname: van Eijsden
authors.forename: Robin A
authors.initials: RA
authors.lastname: de Graaf
authors.forename: Rick M
authors.initials: RM
authors.lastname: Dijkhuizen
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D023421:Models, Animal; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009483:Neuropsychological Tests; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000378:metabolism*
chemical_list: D002247:Carbon Isotopes; D005973:Glutamine; D001224:Aspartic Acid; D019344:Lactic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate; D005947:Glucose