Genetic mechanisms underlying local spontaneous brain activity in episodic migraine.

Advances in neuroimaging techniques during the past few decades have captured impaired functional brain activity in migraine disorders, yet the molecular mechanisms accounting for its alterations in migraine remain largely unknown. A total of 27 patients with episodic migraine (EM) and 30 matched healthy controls (HCs) underwent resting-state functional and structural magnetic resonance imaging (MRI) scans. Regional homogeneity (ReHo), low-frequency fluctuations (ALFF), and fractional amplitude of low-frequency fluctuations (fALFF) of fMRI were compared between the two groups. Based on the Allen Human Brain Atlas and risk genes in migraine, we identified gene expression profiles associated with ReHo alterations in EM. Compared with HCs, patients with EM showed increased ReHo in the left orbital part of the superior frontal gyrus (P < 0.05, cluster-level FWE-corrected). The expression profiles of 16 genes were significantly correlated with ReHo alterations in EM (P < 0.05/5,013, Bonferroni corrected). These genes were mainly enriched for transcription regulation, synaptic transmission, energy metabolism, and migraine disorders. Furthermore, the neural activation was positively correlated with Hamilton Rating Scale for Anxiety (HAMA) scores. To test the stability of our results, we repeated our procedure by using ALFF and fALFF and found these results had a high degree of consistency. Overall, these findings not only demonstrated that regional brain activity was increased in patients with EM, which was associated with emotional regulation but also provided new insights into the genetic mechanisms underlying these changes in migraine.

Gut microbiota changes and biological mechanism in hepatocellular carcinoma after transarterial chemoembolization treatment.

Background and aims: Intestinal flora is closely associated with the occurrence and development of hepatocellular carcinoma (HCC). However, gut microbial changes and biological mechanisms in HCC after transarterial chemoembolization (TACE) treatment are rarely reported. Methods: We evaluated changes in intestinal flora after TACE in rabbit HCC models and assessed the impact of these changes on the disease. Twenty-four rabbit VX2 HCC models were established and intestinal flora structures, intestinal barrier function, changes in blood lipopolysaccharide (LPS) levels, Toll-like receptor 4 (TLR4), Cyclooxygenase-2 (COX-2), and p-signal transducer and activator of transcription 3(p-STAT3) protein expression levels were studied after TACE treatment. Results: Compared with healthy rabbits, the intestinal flora in HCC models exhibited structural changes; intestinal barrier function was decreased, and increased LPS levels entered the circulation. A short-term follow-up after TACE showed the procedure partially reversed the intestinal microflora disorder caused by the tumor: intestinal barrier and liver functions were improved, intestinal LPS levels in the blood were reduced, and liver metabolism toward LPS was enhanced. Correlation analyses of the first 75 significantly changed bacteria with clinical factors showed that harmful bacteria had decreased and beneficial bacteria increased. Blood LPS levels and downstream signaling molecule TLR4, COX-2, and p-STAT3 protein expression levels were reduced, which correlated with tumor drug resistance and invasion capabilities. Conclusions: We first characterized gut microbiota changes and biological mechanisms in HCC after TACE treatment. Our data provide a theoretical research basis for TACE combined with an intestinal flora intervention and systemic chemotherapy.

Overexpression of BDNF in the ventrolateral periaqueductal gray regulates the behavior of epilepsy-migraine comorbid rats.

OBJECTIVE: To investigate the effects of brain-derived neurotrophic factor (BDNF) overexpression in the ventrolateral periaqueductal gray (vlPAG) on behavioral changes in epilepsy-migraine comorbid rats. METHOD: We used an adeno-associated virus (AAV)-mediated vector to supplement BDNF in the vlPAG area prior to the establishment of a pilocarpine-nitroglycerin (Pilo-NTG) combination-induced comorbid model of epilepsy and migraine. Seizure- and migraine-related behaviors were analyzed. Cell loss and apoptosis in vlPAG were detected through hematoxylin-eosin (HE) and TUNEL staining. Immunofluorescence staining analyses were employed to detect expressions of BDNF and its receptor, tyrosine kinase B (TrkB), in vlPAG. Immunohistochemical staining was conducted to detect expressions of c-Fos and calcitonin gene-related peptide (CGRP) in the trigeminal nucleus caudalis (TNC) and trigeminal ganglion (TG). RESULTS: Comparing to control group, AAV-BDNF injected comorbid group showed lower pain sensitivity, scratching head, and spontaneous seizures accompanied by the downregulation of c-Fos labeling neurons and CGRP immunoreactivity in the TNC and TG. However, these changes were still significantly higher in the comorbid group than those in both epilepsy and migraine groups under the same intervention. CONCLUSION: These data demonstrated that supplying BDNF to vlPAG may protect structural and functional abnormalities in vlPAG and provide an antiepileptic and analgesic therapy.

Amplitude of Low-Frequency Fluctuation With Different Clinical Outcomes in Patients With Generalized Tonic-Clonic Seizures.

Background: Generalized tonic-clonic seizures (GTCS) are associated with significant disability and sudden unexpected death when they cannot be controlled. We aimed to explore the underlying neural substrate of the different responses to antiseizure drugs between the seizure-free (SF) and non-seizure-free (NSF) patients with GTCS through the amplitude of low-frequency fluctuation (ALFF) method. Methods: We calculated ALFF among the SF group, NSF group, and healthy controls (HCs) by collecting resting-state functional magnetic resonance imaging (rs-fMRI) data. One-way ANOVA was used to compare the ALFF of the three groups, and post-hoc analysis was done at the same time. Pearson's correlation analysis between ALFF in the discrepant brain areas and the clinical characteristics (disease course and age of onset of GTCS) was calculated after then. Results: A significant group effect was found in the right fusiform gyrus (R.FG), left fusiform gyrus (L.FG), left middle occipital gyrus (L.MOG), right inferior frontal gyrus (R.IFG), right precentral gyrus (R.PreG), right postcentral gyrus (R.PostG), and left calcarine sulcus (L.CS). The SF and NSF groups both showed increased ALFF in all discrepant brain areas compared to HCs except the R.IFG in the NSF group. Significantly higher ALFF in the bilateral FG and lower ALFF in the R.IFG were found in the NSF group compared to the SF group. Conclusions: Higher ALFF in the bilateral FG were found in the NSF group compared to the SF and HC groups. Our findings indicate that abnormal brain activity in the FG may be one potential neural substrate to interpret the failure of seizure control in patients with GTCS.