N-acetylaspartate Decrease in Acute Stage of Ischemic Stroke:A Perspective from Experimental and Clinical Studies

Zou

BMC Complement Altern Med

et al. 2016

BackgroundBuyang Huanwu Decoction (BYHWD) is a Traditional Chinese Medicine (TCM) formula for treating stroke-induced disability. Xiaoshuan enteric-coated capsule (XSECC), derived from the formula BYHWD, is a drug approved by the China Food and Drug Administration (CFDA) for stroke management. To further investigate the potential protective effects of XSECC on neurovascular functions, we endeavour to monitor the neurovascular functions using multimodal magnetic resonance imaging (MRI) and evaluated histopathological changes of neurovascular unit (NVU) after stroke.MethodsIschemic stroke was induced by permanent middle cerebral artery occlusion (pMCAO). XSECC (420 mg/kg) was orally administered 2 h after stroke and daily thereafter. T2-weighted imaging (T2WI), T2 relaxometry mapping and diffusion tensor imaging (DTI) were used to measure cerebral infarct volume, edema and white matter fiber integrity, respectively. Neurochemical metabolite levels were monitored by 1H-magnetic resonance spectroscopy (1H-MRS). Arterial spin labeling (ASL) – cerebral blood flow (CBF) measurements and structural magnetic resonance angiography (MRA) images provided real-time and dynamic information about vascular hemodynamic dysfunction on the 3rd, 7th and 14th days after pMCAO. At the last imaging time point, immunohistochemistry, immunofluorescence as well as transmission electron microscopy (TEM) were used to test the microscopic and ultrastructural changes of NVU.ResultsT2WI, T2 relaxometry mapping and Fractional anisotropy (FA) in DTI showed that XSECC significantly reduced cerebral infarct volume, relieved edema and alleviated nerve fiber injuries, respectively. 1H-MRS provided information about improvement of neuronal/glial metabolism after XSECC treatment. Moreover, ASL – CBF measurements combined with MRA showed that XSECC significantly increased CBF and vascular signal strength and alleviated ischemia-induced morphological changes of arteries in ischemic hemisphere within 14 days after stroke. In addition, neuron specific nuclear protein (NeuN), glial fibrillary acidic protein (GFAP), CD34 staining and TEM detection indicated that XSECC not only ameliorated neuronal injury, but also reduced endothelial damage and inhibited astrocyte proliferation.ConclusionsOur results suggested that XSECC has multi-target neurovascular protective effects on ischemic stroke, which may be closely correlated with the improvement of cerebral blood supply and neuronal/glial metabolism.

Section: Resultsmentioning

confidence: 99%

“…1 H-MRS indicates the information of neuronal/glial metabolism [ 35 , 36 ]. 1 H-MRS of the rat brain was acquired using a PRESS sequence with the following parameters: TR/TE = 1500/135 ms, voxel = 5 cm × 4 cm × 4 cm.…”

Section: Methodsmentioning

confidence: 99%

Effects of Xiaoshuan enteric-coated capsule on neurovascular functions assessed by quantitative multiparametric MRI in a rat model of permanent cerebral ischemia

Zou

BMC Complement Altern Med

et al. 2016

Arch Dis Child Fetal Neonatal Ed

“…Both NAA and NAAG synthesis in neurons is ATP dependent and hypoxia–ischaemia initiates a decline in NAA/NAAG within hours. Much of the NAA synthesised in the neuron is transported to oligodendrocytes where it is a substrate source for myelin synthesis; it is likely that decreases in NAA following NE will lead to a reduced myelination 14. In adult stroke, NAA levels can predict the fate of an acute ischaemic lesion with more accuracy than DWI 39 40.…”

Section: Discussionmentioning

confidence: 99%

“…A potential benefit of including Thr, in addition to lactate, in the spectral analysis is improvement in the spectral fit in the region around 1.3 ppm in cases where lactate is raised. Similarly, including both NAA and NAA glutamate (NAAG, an abundant neurotransmitter released from axonal terminals with neuronal activity and hydrolysed to NAA and glutamate; NAA+NAAG= total NAA (tNAA)) improves fitting in the region around 2.0 ppm at field strength of 3T 14…”

Section: Introductionmentioning

confidence: 99%

Proton magnetic resonance spectroscopy lactate/N-acetylaspartate within 2 weeks of birth accurately predicts 2-year motor, cognitive and language outcomes in neonatal encephalopathy after therapeutic hypothermia

Mitra

Kendall

Bainbridge

et al. 2018

ObjectiveBrain proton (1H) magnetic resonance spectroscopy (MRS) lactate/N-acetylaspartate (Lac/NAA) peak area ratio is used for prognostication in neonatal encephalopathy (NE). At 3 Tesla in NE babies, the objectives were to assess: (1) sensitivity and specificity of basal ganglia and thalamus (BGT) 1H MRS Lac/NAA for the prediction of Bayley III outcomes at 2 years using optimised metabolite fitting (Tarquin) with threonine and total NAA; (2) prediction of motor outcome with diffusion-weighted MRI; (3) BGT Lac/NAA correlation with the National Institute of Child Health and Human Development (NICHD) MRI score.Subjects and methods55 (16 inborn, 39 outborn) infants at 39w+5 d (35w+5d–42w+0d) with NE admitted between February 2012 and August 2014 to University College London Hospitals for therapeutic hypothermia underwent MRI and 1H MRS at 3T on day 2–14 (median day 5). MRIs were scored. Bayley III was assessed at 24 (22–26) months.Results16 babies died (1 inborn, 15 outborn); 20, 19 and 21 babies had poor motor, cognitive and language outcomes. Using a threshold of 0.39, sensitivity and specificity of BGT Lac/NAA for 2-year motor outcome was 100% and 97%, cognition 90% and 97% and language 81% and 97%, respectively. Sensitivity and specificity for motor outcome of mean diffusivity (threshold 0.001 mm2/s) up to day 9 was 72% and 100% and fractional anisotropy (threshold 0.198) was 39% and 94%, respectively. Lac/NAA correlated with BGT injury on NICHD scores (2A, 2B, 3).ConclusionBGT Lac/NAA on 1H MRS at 3T within 14 days accurately predicts 2-year motor, cognitive and language outcome and may be a marker directing decisions for therapies after cooling.

“…The ratio between NAA versus total creatine (NAA/Cre), have been found to be clinically useful, since the latter usually remains constant ( Miller, 1991 ). Most clinical studies using MRS have reported decreases in NAA levels (e.g., ischemia ( Berthet et al, 2014 ), stroke ( Igarashi et al, 2015 ), multiple sclerosis ( Aboul-Enein et al, 2010 ), traumatic brain injury ( Moffett et al, 2013 ). Impairments of energy metabolism decrease NAA levels in the brain.…”

Section: Discussionmentioning

confidence: 99%

A ‘complex’ of brain metabolites distinguish altered chemistry in the cingulate cortex of episodic migraine patients

Becerra

Veggeberg

Prescot

et al. 2016

NeuroImage: Clinical

Despite the prevalence of migraine, the pathophysiology of the disease remains unclear. Current understanding of migraine has alluded to the possibility of a hyperexcitable brain. The aim of the current study is to investigate human brain metabolite differences in the anterior cingulate cortex (ACC) during the interictal phase in migraine patients. We hypothesized that there may be differences in levels of excitatory neurotransmitters and/or their derivatives in the migraine cohort in support of the theory of hyperexcitability in migraine. 2D J-resolved proton magnetic resonance spectroscopy (1H-MRS) data were acquired on a 3 Tesla (3 T) MRI from a voxel placed over the ACC of 32 migraine patients (MP; 23 females, 9 males, age 33 ± 9.6 years) and 33 healthy controls (HC; 25 females, 8 males, age 32 ± 9.6 years). Amplitude correlation matrices were constructed for each subject to evaluate metabolite discriminability. ProFit-estimated metabolite peak areas were normalized to a water reference signal to assess subject differences. The initial analysis of variance (ANOVA) was performed to test for group differences for all metabolites/creatine (Cre) ratios between healthy controls and migraineurs but showed no statistically significant differences. In addition, we used a multivariate approach to distinguish migraineurs from healthy subjects based on the metabolite/Cre ratio. A quadratic discriminant analysis (QDA) model was used to identify 3 metabolite ratios sufficient to minimize minimum classification error (MCE). The 3 selected metabolite ratios were aspartate (Asp)/Cre, N-acetyl aspartate (NAA)/Cre, and glutamine (Gln)/Cre. These findings are in support of a ‘complex’ of metabolite alterations, which may underlie changes in neuronal chemistry in the migraine brain. Furthermore, the parallel changes in the three-metabolite ‘complex’ may confer more subtle but biological processes that are ongoing. The data also support the current theory that the migraine brain is hyperexcitable even in the interictal state.