Plasma Lipolysis and Changes in Plasma and Cerebrospinal Fluid Signaling Lipids Reveal Abnormal Lipid Metabolism in Chronic Migraine.

BACKGROUND: Lipids are a primary storage form of energy and the source of inflammatory and pain signaling molecules, yet knowledge of their importance in chronic migraine (CM) pathology is incomplete. We aim to determine if plasma and cerebrospinal fluid (CSF) lipid metabolism are associated with CM pathology. METHODS: We obtained plasma and CSF from healthy controls (CT, n = 10) or CM subjects (n = 15) diagnosed using the International Headache Society criteria. We measured unesterified fatty acid (UFA) and esterified fatty acids (EFAs) using gas chromatography-mass spectrometry. Glycerophospholipids (GP) and sphingolipid (SP) levels were determined using LC-MS/MS, and phospholipase A2 (PLA2) activity was determined using fluorescent substrates. RESULTS: Unesterified fatty acid levels were significantly higher in CM plasma but not in CSF. Unesterified levels of five saturated fatty acids (SAFAs), eight monounsaturated fatty acids (MUFAs), five ω-3 polyunsaturated fatty acids (PUFAs), and five ω-6 PUFAs are higher in CM plasma. Esterified levels of three SAFAs, eight MUFAs, five ω-3 PUFAs, and three ω-6 PUFAs, are higher in CM plasma. The ratios C20:4n-6/homo-γ-C20:3n-6 representative of delta-5-desaturases (D5D) and the elongase ratio are lower in esterified and unesterified CM plasma, respectively. In the CSF, the esterified D5D index is lower in CM. While PLA2 activity was similar, the plasma UFA to EFA ratio is higher in CM. Of all plasma GP/SPs detected, only ceramide levels are lower (p = 0.0003) in CM (0.26 ± 0.07%) compared to CT (0.48 ± 0.06%). The GP/SP proportion of platelet-activating factor (PAF) is significantly lower in CM CSF. CONCLUSIONS: Plasma and CSF lipid changes are consistent with abnormal lipid metabolism in CM. Since plasma UFAs correspond to diet or adipose tissue levels, higher plasma fatty acids and UFA/EFA ratios suggest enhanced adipose lipolysis in CM. Differences in plasma and CSF desaturases and elongases suggest altered lipid metabolism in CM. A lower plasma ceramide level suggests reduced de novo synthesis or reduced sphingomyelin hydrolysis. Changes in CSF PAF suggest differences in brain lipid signaling pathways in CM. Together, this pilot study shows lipid metabolic abnormality in CM corresponding to altered energy homeostasis. We propose that controlling plasma lipolysis, desaturases, elongases, and lipid signaling pathways may relieve CM symptoms.

Alpha desynchronization/synchronization during working memory testing is compromised in acute mild traumatic brain injury (mTBI).

Diagnosing and monitoring recovery of patients with mild traumatic brain injury (mTBI) is challenging because of the lack of objective, quantitative measures. Diagnosis is based on description of injuries often not witnessed, subtle neurocognitive symptoms, and neuropsychological testing. Since working memory (WM) is at the center of cognitive functions impaired in mTBI, this study was designed to define objective quantitative electroencephalographic (qEEG) measures of WM processing that may correlate with cognitive changes associated with acute mTBI. First-time mTBI patients and mild peripheral (limb) trauma controls without head injury were recruited from the emergency department. WM was assessed by a continuous performance task (N-back). EEG recordings were obtained during N-back testing on three occasions: within five days, two weeks, and one month after injury. Compared with controls, mTBI patients showed abnormal induced and evoked alpha activity including event-related desynchronization (ERD) and synchronization (ERS). For induced alpha power, TBI patients had excessive frontal ERD on their first and third visit. For evoked alpha, mTBI patients had lower parietal ERD/ERS at the second and third visits. These exploratory qEEG findings offer new and non-invasive candidate measures to characterize the evolution of injury over the first month, with potential to provide much-needed objective measures of brain dysfunction to diagnose and monitor the consequences of mTBI.

Dapdiamides, tripeptide antibiotics formed by unconventional amide ligases.

Construction of a genomic DNA library from Pantoea agglomerans strain CU0119 and screening against the plant pathogen Erwinia amylovora yielded a new family of antibiotics, dapdiamides A-E (1-5). The structures were established through 2D-NMR experiments and mass spectrometry, as well as the synthesis of dapdiamide A (1). Transposon mutagenesis of the active cosmid allowed identification of the biosynthetic gene cluster. The dapdiamide family's promiscuous biosynthetic pathway contains two unconventional amide ligases that are predicted to couple its constituent monomers.