Specific neurochemicals measured with proton magnetic resonance spectroscopy (1H-MRS) may serve as biomarkers of pathological mechanism in the brain. We used high field in vivo 1H-MRS to measure a detailed neurochemical profile after experimental traumatic brain injury (TBI) in rats. We characterized neurochemical changes in the contused cortex and the normal-appearing perilesional hippocampus over a time course from 1 hour to 2 weeks after injury. We found significant changes in 19 out of 20 neurochemicals in the cortex, and 9 out of 20 neurochemicals in the hippocampus. These changes provide evidence of altered cellular metabolic status after TBI, with specific compounds proposed to reflect edema, excitotoxicity, neuronal and glial integrity, mitochondrial status and bioenergetics, oxidative stress, inflammation, and cell membrane disruption. Our results support the utility of 1H-MRS for monitoring cellular mechanisms of TBI pathology in animal models, and the potential of this approach for preclinical evaluation of novel therapies.

Background and Purpose Our goal was to investigate whether certain metabolites, specific to neurons, glial cells, or the neuronal-glial neurotransmission system, in primary motor cortices (M1), are altered and correlated with clinical motor severity in chronic stroke. Methods Fourteen survivors of a single ischemic stroke located outside the M1 and 14 age-matched healthy control subjects were included. At >6 months after stroke, N-acetylaspartate, myo-inositol, and glutamate/glutamine were measured using proton magnetic resonance spectroscopic imaging (in-plane resolution=5×5 mm2) in radiologically normal-appearing gray matter of the hand representation area, identified by functional MRI, in each M1. Metabolite concentrations and analyses of metabolite correlations within M1 were determined. Relationships between metabolite concentrations and arm motor impairment were also evaluated. Results The stroke survivors showed lower N-acetylaspartate and higher myo-inositol across ipsilesional and contral-esional M1 compared with control subjects. Significant correlations between N-acetylaspartate and glutamate/glutamine were found in either M1. Ipsilesional N-acetylaspartate and glutamate/glutamine were positively correlated with arm motor impairment and contralesional N-acetylaspartate with time after stroke. Conclusions Our preliminary data demonstrated significant alterations of neuronal-glial interactions in spared M1 with the ipsilesional alterations related to stroke severity and contralesional alterations to stroke duration. Thus, MR spectroscopy might be a sensitive method to quantify relevant metabolite changes after stroke and consequently increase our knowledge of the factors leading from these changes in spared motor cortex to motor impairment after stroke.

All 4 measurement techniques demonstrated a good to moderately high degree of intra- and interobserver reliability. Highest reliability was noted in the assessment of T2-weighted sequences and axial MRI. Our results show that the measurements of MCC, MSCC, and CR are sufficiently reliable and correlate well with clinical severity of cervical myelopathy.

Background Although functional imaging and neurophysiological approaches reveal alterations in motor and premotor areas after stroke, insights into neurobiological events underlying these alterations are limited in human studies. Objective We tested whether cerebral metabolites related to neuronal and glial compartments are altered in the hand representation in bilateral motor and premotor areas and correlated with distal and proximal arm motor impairment in hemiparetic persons. Methods In twenty participants at >6 months post-onset of a subcortical ischemic stroke and sixteen age and sex-matched healthy controls, the concentrations of N-acetylaspartate and myoinositol were quantified by proton magnetic resonance spectroscopy (1H-MRS). Regions of interest, identified by functional MRI, included primary (M1), dorsal premotor (PMd), and supplementary (SMA) motor areas. Relationships between metabolite concentrations and distal (hand) and proximal (shoulder/elbow) motor impairment using Fugl-Meyer Upper Extremity (FMUE) subscores were explored. Results N-acetylaspartate was lower in M1 (p=0.04) and SMA (p=0.004) and myo-inositol was higher in M1 (p=0.003) and PMd (p=0.03) in the injured (ipsilesional) hemisphere after stroke compared to the left hemisphere in controls. N-acetylaspartate in ipsilesional M1 was positively correlated with hand FMUE subscores (p=0.04). Significant positive correlations were also found between N-acetylaspartate in ipsilesional M1, PMd, and SMA and in contralesional M1 and shoulder/elbow FMUE subscores (p=0.02, 0.01, 0.02 and 0.02 respectively). Conclusions Our preliminary results demonstrated that 1H-MRS is a sensitive method to quantify relevant neuronal changes in spared motor cortex after stroke, and consequently increase our knowledge of the factors leading from these changes to arm motor impairment.