Potential of serum metabolites for diagnosing post-stroke cognitive impairment

Liu, Min; Zhou, Kai-ge; Li, Hailong; Dong, Xin; Tan, Guangguo; Chai, Yifeng; Wang, Weizhong; Bi, Xiaoying

doi:10.1039/c5mb00470e

Cited by 58 publications

(71 citation statements)

References 59 publications

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“…The application of metabolomic tools to study brain diseases have greatly enhanced our understanding of different pathologies, for example; we demonstrated the upregulation of the ceramide "Cer(d18:0/18:0)" and phosphocreatine following transient ischemia-reperfusion in mice using a mass spectrometric imaging approach 15 . Several studies have highlighted an array of small molecules, amino acids and lipids that were linked to stroke severity, progression or post-stroke cognitive deficits [23][24][25] . Moreover, linoleic acid…”

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confidence: 99%

Metabolic basis of neuronal vulnerability to ischemia; an in vivo untargeted metabolomics approach

Rashad

Saigusa

Yamazaki

et al. 2020

Sci Rep

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Understanding the root causes of neuronal vulnerability to ischemia is paramount to the development of new therapies for stroke. Transient global cerebral ischemia (tGCI) leads to selective neuronal cell death in the CA1 sub-region of the hippocampus, while the neighboring CA3 sub-region is left largely intact. By studying factors pertaining to such selective vulnerability, we can develop therapies to enhance outcome after stroke. Using untargeted liquid chromatography-mass spectrometry, we analyzed temporal metabolomic changes in CA1 and CA3 hippocampal areas following tGCI in rats till the setting of neuronal apoptosis. 64 compounds in CA1 and 74 in CA3 were found to be enriched and statistically significant following tGCI. Pathway analysis showed that pyrimidine and purine metabolism pathways amongst several others to be enriched after tGCI in CA1 and CA3. Metabolomics analysis was able to capture very early changes following ischemia. We detected 6 metabolites to be upregulated and 6 to be downregulated 1 hour after tGCI in CA1 versus CA3. Several metabolites related to apoptosis and inflammation were differentially expressed in both regions after tGCI. We offer a new insight into the process of neuronal apoptosis, guided by metabolomic profiling that was not performed to such an extent previously.Metabolomics is the study of metabolite composition of cells, tissues or biological fluids. Recent technological advances in this field has allowed the discovery of new biomarkers of diseases such as coronary artery disease, septic shock and brain tumors as well as the discovery of new drugs 1-5 . Metabolomic analysis has also deepened our understanding of several disease models, leading to the discovery of new pathways or targets for drug therapies that could later be applied to the treatment of various diseases [6][7][8][9][10][11] . Indeed, metabolomics are closer to the phenotype of a given disease compared with transcriptomic or proteomic analysis, both of which are prone to downstream modifications and changes in activities 1,12 .Several techniques, tools and software platforms exist to study metabolomics, all of which complement each other 13 . The application of these tools has greatly enhanced our understanding of the pathophysiology of diseases in almost every field of research 14 . In the field of neuroscience, metabolomic analysis is used to study stroke 15 , brain tumors 16 , traumatic brain injury (TBI) 17,18 , neurodegenerative diseases 19 , hypoxic-ischemic encephalopathy 20 and depression 21 to name a few 22 . The application of metabolomic tools to study brain diseases have greatly enhanced our understanding of different pathologies, for example; we demonstrated the upregulation of the ceramide "Cer(d18:0/18:0)" and phosphocreatine following transient ischemia-reperfusion in mice using a mass spectrometric imaging approach 15 . Several studies have highlighted an array of small molecules, amino acids and lipids that were linked to stroke severity, progression or post-stroke cognitive deficits [23][...

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mentioning

confidence: 99%

Metabolic basis of neuronal vulnerability to ischemia; an in vivo untargeted metabolomics approach

Rashad

Saigusa

Yamazaki

et al. 2020

Sci Rep

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“…These results were confirmed by Moretti and colleagues, who found a higher homocysteine level in VaD patients, but also a significantly vitamin D deficiency and low levels of folate [16], as well as in elderly patients with fatigue [56]. Liu and co-workers suggested a biomarker panel of three metabolites (glutamine, kynurenine, and lysophosphatidylcholines) to predict the post-stroke cognitive impairment [12].…”

Section: Serummentioning

confidence: 59%

“…Therefore, a total of 46 papers were eventually included in this study ( Figure 1) and the main findings are summarized in Table 1. More in details, 8 studies deal with serum biomarkers [9][10][11][12][13][14][15][16], 10 with cerebrospinal fluid (CSF) [17][18][19][20][21][22][23][24][25][26], 4 with neuroimaging [27][28][29][30], 6 with histopathology [31][32][33][34][35][36], and 14 with transcranial magnetic stimulation (TMS) [37][38][39][40][41][42][43][44][45][46][47][48][49][50]; 4 studies included more than one technique: one studied both serum and CSF markers [51], two both serum and neuroimaging [52,53], and one both CSF and neuroimaging…”

Section: Resultsmentioning

confidence: 99%

Update on the Neurobiology of Vascular Cognitive Impairment: From Lab to Clinic

Vinciguerra

Lanza

Puglisi

et al. 2020

IJMS

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In the last years, there has been a significant growth in the literature exploring the pathophysiology of vascular cognitive impairment (VCI). As an "umbrella term" encompassing any degree of vascular-related cognitive decline, VCI is deemed to be the most common cognitive disorder in the elderly, with a significant impact on social and healthcare expenses. Interestingly, some of the molecular, biochemical, and electrophysiological abnormalities detected in VCI seem to correlate with disease process and progression, eventually promoting an adaptive plasticity in some patients and a maladaptive, dysfunctional response in others. However, the exact relationships between vascular lesion, cognition, and neuroplasticity are not completely understood. Recent findings point out also the possibility to identify a panel of markers able to predict cognitive deterioration in the so-called "brain at risk" for vascular or mixed dementia. This will be of pivotal importance when designing trials of disease-modifying drugs or non-pharmacological approaches, including non-invasive neuromodulatory techniques. Taken together, these advances could make VCI a potentially preventable cause of both vascular and degenerative dementia in late life. This review provides a timely update on the recent serological, cerebrospinal fluid, histopathological, imaging, and neurophysiological studies on this "cutting-edge" topic, including the limitations, future perspectives and translational implications in the diagnosis and management of VCI patients.

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“…None of these studies, however, have identified and characterized in vivo ECTP plasma metabolites. Apart from these studies, a body of previous work has utilized LC/MS‐based metabolomic approaches to support the treatment of a variety of neuropsychiatric disorders including stroke, bipolar disorder, and autism . Very few studies, however, have ECTP blood plasma concentration and response prediction .…”

Section: Introductionmentioning

confidence: 99%

“…Apart from these studies, a body of previous work has utilized LC/MS-based metabolomic approaches to support the treatment of a variety of neuropsychiatric disorders including stroke, bipolar disorder, and autism. [24][25][26][27][28] Very few studies, however, have ECTP blood plasma concentration and response prediction. 29,30 One previous study demonstrated that early improvement and ECTP serum concentration could be used to predict the effectiveness of antidepressant drug response in MDD patients.…”

mentioning

confidence: 99%

Liquid chromatography/mass spectrometry‐based plasma metabolic profiling study of escitalopram in subjects with major depressive disorder

Bandu

Lee

et al. 2018

J Mass Spectrom

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Liquid chromatography-mass spectrometry (LC-MS) method revealed the plasma metabolite profiles in major depressive disorder patients treated with escitalopram (ECTP) (n = 7). Depression severity was assessed according to the 17-item Hamilton Depression Rating Scale. Metabolic profiles were derived from major depressive disorder subject blood samples collected after ECTP treatment. Blood plasma was separated and processed in order to effectively extract metabolites, which were then analyzed using LC-MS. We identified 19 metabolites and elucidated their structures using LC-tandem MS (LC-MS/MS) combined with elemental compositions derived from accurate mass measurements. We further used online H/D exchange experiments to verify the structural elucidations of each metabolite. Identifying molecular metabolites may provide critical insights into the pharmacological and clinical effects of ECTP treatment and may also provide useful information informing the development of new antidepressant treatments. These detailed plasma metabolite analyses may also be used to identify optimal dose concentrations in psychopharmacotherapeutic treatment through drug monitoring, as well as forming the basis for response predictions in depressed subjects.

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Potential of serum metabolites for diagnosing post-stroke cognitive impairment

Cited by 58 publications

References 59 publications

Metabolic basis of neuronal vulnerability to ischemia; an in vivo untargeted metabolomics approach

Metabolic basis of neuronal vulnerability to ischemia; an in vivo untargeted metabolomics approach

Update on the Neurobiology of Vascular Cognitive Impairment: From Lab to Clinic

Liquid chromatography/mass spectrometry‐based plasma metabolic profiling study of escitalopram in subjects with major depressive disorder

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