Pattern recognition analysis of proton nuclear magnetic resonance spectra of postmortem cerebrospinal fluid from rats with drug-induced seizure or coma

Kanawaku, Yoshimasa; Hirakawa, Keiko; Koike, Kazuhiko; Kanetake, Jun; Ohno, Youkichi

doi:10.1016/j.legalmed.2017.01.004

Cited by 4 publications

(3 citation statements)

References 43 publications

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“…CSF/ECSB metabolic profile could be investigate through metabolomic way or focusing on specific compounds or pathways, and the former is more comprehensive. There has been a metabolomic research demonstrating that CSF composition is significantly divergent in anesthetic-induced coma from that of normal or pentylenetetrazol-treated epileptic rats [ 34 ]. Nevertheless, clinical studies of the gross CSF metabolome alterations in SAH patients after sedative treatment were absent [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal fluid metabolic profiling reveals divergent modulation of pentose phosphate pathway by midazolam, propofol and dexmedetomidine in patients with subarachnoid hemorrhage: a cohort study

Wang

et al. 2022

BMC Anesthesiol

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Background Agitation is common in subarachnoid hemorrhage (SAH), and sedation with midazolam, propofol and dexmedetomidine is essential in agitation management. Previous research shows the tendency of dexmedetomidine and propofol in improving long-term outcome of SAH patients, whereas midazolam might be detrimental. Brain metabolism derangement after SAH might be interfered by sedatives. However, how sedatives work and whether the drugs interfere with patient outcome by altering cerebral metabolism is unclear, and the comprehensive view of how sedatives regulate brain metabolism remains to be elucidated. Methods For cerebrospinal fluid (CSF) and extracellular space of the brain exchange instantly, we performed a cohort study, applying CSF of SAH patients utilizing different sedatives or no sedation to metabolomics. Baseline CSF metabolome was corrected by selecting patients of the same SAH and agitation severity. CSF components were analyzed to identify the most affected metabolic pathways and sensitive biomarkers of each sedative. Markers might represent the outcome of the patients were also investigated. Results Pentose phosphate pathway was the most significantly interfered (upregulated) pathway in midazolam (p = 0.0000107, impact = 0.35348) and propofol (p = 0.00000000000746, impact = 0.41604) groups. On the contrary, dexmedetomidine decreased levels of sedoheptulose 7-phosphate (p = 0.002) and NADP (p = 0.024), and NADP is the key metabolite and regulator in pentose phosphate pathway. Midazolam additionally augmented purine synthesis (p = 0.00175, impact = 0.13481) and propofol enhanced pyrimidine synthesis (p = 0.000203, impact = 0.20046), whereas dexmedetomidine weakened pyrimidine synthesis (p = 0.000000000594, impact = 0.24922). Reduced guanosine diphosphate (AUC of ROC 0.857, 95%CI 0.617–1, p = 0.00506) was the significant CSF biomarker for midazolam, and uridine diphosphate glucose (AUC of ROC 0.877, 95%CI 0.631–1, p = 0.00980) for propofol, and succinyl-CoA (AUC of ROC 0.923, 95%CI 0.785–1, p = 0.000810) plus adenosine triphosphate (AUC of ROC 0.908, 95%CI 0.6921, p = 0.00315) for dexmedetomidine. Down-regulated CSF succinyl-CoA was also associated with favorable outcome (AUC of ROC 0.708, 95% CI: 0.524–0.865, p = 0.029333). Conclusion Pentose phosphate pathway was a crucial target for sedatives which alter brain metabolism. Midazolam and propofol enhanced the pentose phosphate pathway and nucleotide synthesis in poor-grade SAH patients, as presented in the CSF. The situation of dexmedetomidine was the opposite. The divergent modulation of cerebral metabolism might further explain sedative pharmacology and how sedatives affect the outcome of SAH patients.

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Section: Introductionmentioning

confidence: 99%

Cerebrospinal fluid metabolic profiling reveals divergent modulation of pentose phosphate pathway by midazolam, propofol and dexmedetomidine in patients with subarachnoid hemorrhage: a cohort study

Wang

et al. 2022

BMC Anesthesiol

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“…Metabolomics has already been used to investigate changes in the metabolome after seizures [5] or the effect of anti-seizure drug treatment [6] in patients. Most studies, however, focus on brain metabolites by studying brain tissue of a chemo convulsive animal model [7][8][9][10][11][12]. One of these studies focuses on the participation of cysteine during a seizure and treatment of epilepsy in a mouse model [7].…”

Section: Introductionmentioning

confidence: 99%

“…However, tissue analysis is challenging because of several analytical and technical issues [13]. Therefore, circulating blood-based biomarkers are potentially interesting as plasma is more easily accessible than, for instance, cerebrospinal fluid [10,14,15]. At the moment, only a few studies make use of plasma metabolite profiling in epilepsy by using an animal model.…”

Section: Introductionmentioning

confidence: 99%

CE-MS metabolic profiling of volume-restricted plasma samples from an acute mouse model for epileptic seizures to discover potentially involved metabolomic features

Segers

Zhang

Aourz

et al. 2020

Talanta

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Currently, a high variety of analytical techniques to perform metabolomics is available. One of these techniques is capillary electrophoresis coupled to mass spectrometry (CE-MS), which has emerged as a rather strong analytical technique for profiling polar and charged compounds. This work aims to discover with CE-MS potential metabolic consequences of evoked seizures in plasma by using a 6Hz acute corneal seizure mouse model. CE-MS is an appealing technique because of its capability to handle very small sample volumes, such as the 10 μL plasma samples obtained using capillary microsampling in this study. After liquid-liquid extraction, the samples were analyzed with CE-MS using low-pH separation conditions, followed by data analysis and biomarker identification. Both electrically induced seizures showed decreased values of methionine, lysine, glycine, phenylalanine, citrulline, 3-methyladenine and histidine in mice plasma. However, a second provoked seizure, 13 days later, showed a less pronounced decrease of the mean concentrations of these plasma metabolites, demonstrated by higher fold change ratios. Other obtained markers that can be related to seizure activities based on literature data, are isoleucine, serine, proline, tryptophan, alanine, arginine, valine and asparagine. Most amino acids showed relatively stable plasma concentrations between the basal levels (Time point 1) and after the 13-day wash-out period (Time point 3), which suggests its effectiveness. Overall, this work clearly demonstrated the possibility of profiling metabolite consequences related to seizure activities of an intrinsically low amount of body fluid using CE-MS. It would be useful to investigate and validate, in the future, the known and unknown metabolites in different animal models as well as in humans.

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NMR spectroscopy for forensic samples

Hussain¹,

Rawtani²,

Pandey³

et al. 2021

Handbook of Analytical Techniques for Forensic Samples

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Pattern recognition analysis of proton nuclear magnetic resonance spectra of postmortem cerebrospinal fluid from rats with drug-induced seizure or coma

Cited by 4 publications

References 43 publications

Cerebrospinal fluid metabolic profiling reveals divergent modulation of pentose phosphate pathway by midazolam, propofol and dexmedetomidine in patients with subarachnoid hemorrhage: a cohort study

Cerebrospinal fluid metabolic profiling reveals divergent modulation of pentose phosphate pathway by midazolam, propofol and dexmedetomidine in patients with subarachnoid hemorrhage: a cohort study

CE-MS metabolic profiling of volume-restricted plasma samples from an acute mouse model for epileptic seizures to discover potentially involved metabolomic features

NMR spectroscopy for forensic samples

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