Association between dietary carbohydrate intake percentage and epilepsy prevalence in the NHANES 2013-2018: a cross-sectional study.

BACKGROUND: Epilepsy is a neurological disorder characterized by recurrent seizures. We aimed to investigate the association between the percentage of dietary carbohydrate intake (DCI) and epilepsy prevalence among American adults. METHODS: We analyzed the data from 9,584 adults aged 20-80 years who participated in the National Health and Nutrition Examination Survey from 2013 to 2018. Logistic regression was applied to explore the association between the percentage of DCI and epilepsy prevalence. RESULTS: A total of 146 (1.5%) individuals with epilepsy were enrolled in this study. The average age of the participants was 56.4 years, and 5,454 (56.9%) individuals were female. A high DCI was associated with an increased prevalence of epilepsy (odds ratio [OR], 4.56; 95% confidence interval [CI], 1.11-18.69; P = 0.035) after adjusting for age, sex, marital status, race/ethnicity, educational level, family income, body mass index, smoking status, drinking status, hypertension, diabetes, and cardiovascular disease. Stratified analyses indicated a positive correlation between DCI and epilepsy prevalence in adults with different characteristics. Compared with individuals in quartile 1 of DCI (<40.5%), those in quartile 4 (>55.4%) had an adjusted OR for epilepsy of 1.72 (95% CI, 1.09-2.73, P = 0.02, P for trend = 0.012). CONCLUSIONS: A high percentage of DCI was associated with an increased prevalence of epilepsy. The risk of epilepsy increased 3.5-fold with a 1% increase in DCI. These results suggest an important role of DCI in the dietary management of epilepsy.

Temporal alterations of pituitary adenylate cyclase activating polypeptide and its receptors in a rat model induced by recurrent chemical stimulations: Relevant to chronic migraine.

Background: Migraine is a common type of primary headache with disabling brain dysfunction. It has been found that pituitary adenylate cyclase activating polypeptide (PACAP) is involved in the pathogenesis of migraine, however, the role of PACAP and its receptors in chronic migraine remains unclear. Therefore, the present study aimed to explore the changes of PACAP and its receptors in different duration after recurrent dural inflammation soup stimulations and to investigate the co-expression between PACAP and calcitonin gene-related peptide (CGRP). Methods: Adult male rats were implanted with cannula surrounding superior sagittal sinus, which was followed by dural infusion of inflammatory soup (IS) or normal saline (NS). The rats were randomly divided into 4 groups (n = 8 for each group): IS stimulation for seven days (IS-7 group), IS stimulation for 14 days (IS-14 group), IS stimulation for 21 days (IS-21 group), and NS control for 21 days (CON group). The facial mechanical withdrawal threshold was daily measured during the whole experiment. The behavioral changes (ipsilateral and bilateral face grooming behavior) in a plastic cage of rats were observed and recorded. The expression of PACAP, its receptors (PAC1, VPAC1, VPAC2), and CGRP in the trigeminal ganglia (TG) and the trigeminal nucleus caudalis (TNC) was examined by immunohistochemistry. Immunofluorescence was used to explore the co-expression of PACAP, PAC1 receptor, and CGRP after repeated IS administration in the TG. Results: The ipsilateral facial grooming time of IS-21 group displayed an apparent increase than CON group after repeated stimulation on day 2, while significant differences were observed on day 14. No differences were found between the IS-21 and CON group in bilateral facial grooming. Dural IS stimulation induced a significantly decrease in facial mechanical withdrawal thresholds. PACAP positive cells in the regions of TNC were gradually decreased with the IS days increasing. PACAP and PAC1 receptor expression in the TG had a trend of increasing first and then decreasing. There was no significant difference in expression of VPAC1 and VPAC2 in the TG and the TNC. Immunofluorescence showed that PACAP was mainly expressed in TG neurons. PACAP and PAC1 receptor co-expression decreased gradually after repetitive IS stimulation. While the co-expression between PACAP and CGRP reached the peak in IS-7 group after repetitive IS stimulation, and then decreased. Conclusions: This study demonstrated that repetitive chemical stimulations induced a gradual decrease of PACAP in the TNC, while the PACAP and PAC1 receptor expression in TG showed dynamical changes of increasing first and then decreasing after repeated IS administration. These results suggested exhaustion of PACAP could be involved in the duration of chronic migraine and implied PACAP may contribute to the pathology of migraine through the PAC1 receptor, which was associated with CGRP.

Cognitive impairment in a classical rat model of chronic migraine may be due to alterations in hippocampal synaptic plasticity and N-methyl-D-aspartate receptor subunits.

Although migraine is a major global public health problem, its impact on cognitive abilities remains controversial. Thus, the present study investigated the effects of repeated administration of inflammatory soup to the dura of rats, over three weeks, on spatial cognition, hippocampal synaptic plasticity, and the expression of N-methyl-D-aspartate receptor subunits. Additionally, low doses of amitriptyline (5 mg/kg) were applied to assess its therapeutic effects. The inflammatory soup group exhibited significant reductions in the cutaneous stimulation threshold, presence of mild cognitive impairment, and decreased long-term potentiation in right hippocampus. However, amitriptyline improved pain behaviors, enhanced cognitive function, and increased synaptic plasticity in the inflammatory soup rats. On the other hand, the administration of amitriptyline to normal rats negatively influenced synaptic plasticity and reduced the expression of N-methyl-D-aspartate receptor subunits. The present results indicate that inflammatory soup-induced dural nociception led to impairments in spatial cognition that could be attributed to reductions in hippocampal long-term potentiation and the decreased expression of N-methyl-D-aspartate receptor subunits.

Novel gap junction protein beta-1 gene mutation associated with a stroke-like syndrome and central nervous system involvement in patients with X-linked Charcot-Marie-Tooth Type 1: A case report and literature review.

Gap junction protein beta-1 (GJB1) gene mutations lead to X-linked Charcot-Marie-Tooth Type 1 (CMTX1). We studied a Chinese family with CMTX1 and identified a novel GJB1 point mutation. Our patient had a transient stroke-like clinical manifestations and magnetic resonance imaging (MRI) changes. An analysis of the genomic DNA of the proband showed a T to C hemizygous mutation in the GJB1 gene at nucleotide position 380, causing a predicted amino acid change from isoleucine to threonine at codon 127, which predicted structural alterations disrupting the function of the GJB1 protein. This novel point mutation expanded the spectrum of GJB1 mutations known to be associated with CMTX1. We performed a PubMed review of CMTX cases with central nervous system involvement in the English-language literature from the past 20 years, and summarized the demographic data, nucleotide and amino acid changes, clinical characteristics, clinical manifestations, and neuroimaging features.

Dynamic changes in CGRP, PACAP, and PACAP receptors in the trigeminovascular system of a novel repetitive electrical stimulation rat model: Relevant to migraine.

Migraine is the seventh most disabling disorder globally, with prevalence of 11.7% worldwide. One of the prevailing mechanisms is the activation of the trigeminovascular system, and calcitonin gene-related peptide (CGRP) is an important therapeutic target for migraine in this system. Recent studies suggested an emerging role of pituitary adenylate cyclase-activating peptide (PACAP) in migraine. However, the relation between CGRP and PACAP and the role of PACAP in migraine remain undefined. In this study, we established a novel repetitive (one, three, and seven days) electrical stimulation model by stimulating dura mater in conscious rats. Then, we determined expression patterns in the trigeminal ganglion and the trigeminal nucleus caudalis of the trigeminovascular system. Electrical stimulation decreased facial mechanical thresholds, and the order of sensitivity was as follows: vibrissal pad >inner canthus >outer canthus (P < 0.001). The electrical stimulation group exhibited head-turning and head-flicks (P < 0.05) nociceptive behaviors. Importantly, electrical stimulation increased the expressions of CGRP, PACAP, and the PACAP-preferring type 1 (PAC1) receptor in both trigeminal ganglion and trigeminal nucleus caudalis (P < 0.05). The expressions of two vasoactive intestinal peptide (VIP)-shared type 2 (VPAC1 and VPAC2) receptors were increased in the trigeminal ganglion, whereas in the trigeminal nucleus caudalis, their increases were peaked on Day 3 and then decreased by Day 7. PACAP was colocalized with NEUronal Nuclei (NeuN), PAC1, and CGRP in both trigeminal ganglion and the trigeminal nucleus caudalis. Our results demonstrate that the repetitive electrical stimulation model can simulate the allodynia during the migraine chronification, and PACAP plays a role in the pathogenesis of migraine potentially via PAC1 receptor.

Volumetric abnormalities of the brain in a rat model of recurrent headache.

Voxel-based morphometry is used to detect structural brain changes in patients with migraine. However, the relevance of migraine and structural changes is not clear. This study investigated structural brain abnormalities based on voxel-based morphometry using a rat model of recurrent headache. The rat model was established by infusing an inflammatory soup through supradural catheters in conscious male rats. Rats were subgrouped according to the frequency and duration of the inflammatory soup infusion. Tactile sensory testing was conducted prior to infusion of the inflammatory soup or saline. The periorbital tactile thresholds in the high-frequency inflammatory soup stimulation group declined persistently from day 5. Increased white matter volume was observed in the rats three weeks after inflammatory soup stimulation, brainstem in the in the low-frequency inflammatory soup-infusion group and cortex in the high-frequency inflammatory soup-infusion group. After six weeks' stimulation, rats showed gray matter volume changes. The brain structural abnormalities recovered after the stimulation was stopped in the low-frequency inflammatory soup-infused rats and persisted even after the high-frequency inflammatory soup stimulus stopped. The changes of voxel-based morphometry in migraineurs may be the result of recurrent headache. Cognition, memory, and learning may play an important role in the chronification of migraines. Reducing migraine attacks has the promise of preventing chronicity of migraine.

Inhibition of toll-like receptor 4 alleviates hyperalgesia induced by acute dural inflammation in experimental migraine.

Objective Although nociceptive sensitisation is an important pathophysiological process in migraine and migraine chronification, its underlying mechanisms remain unclear. Toll-like receptor 4 (TLR4), a pattern-recognition molecule, has a critical role in both neuropathic pain and morphine tolerance. The present study examined whether elements of the TLR4 pathway contribute to hyperalgesia induced by dural inflammation in rats. Methods A rat model of migraine was established by infusing a dural inflammatory soup. A group pretreated with TAK-242 was used to inhibit the activation of TLR4. The protein levels of TLR4 and its downstream molecules in the trigeminal pathway were examined by Western blot and immunofluorescence. The expression of activated microglia and astrocytes was also analysed. Levels of interleukin-1 beta, tumour necrosis factor-alpha, and brain-derived neurotrophic factor were measured by enzyme-linked immunosorbent assay. Results Acute inflammatory soup infusion induced time-dependent facial mechanical hyperalgesia, which was blocked by TAK-242 pretreatment. The inflammatory soup stimulus increased the production of TLR4 downstream molecules and interleukin-1 beta. Higher levels of microglia activation and brain-derived neurotrophic factor release were observed following the administration of the inflammatory soup but were alleviated by TAK-242. Conclusions These data suggest that the TLR4 signalling pathway promotes hyperalgesia induced by acute inflammatory soup delivery by stimulating the production of proinflammatory cytokines and activating microglia.

Wider range of allodynia in a rat model of repeated dural nociception compared with infraorbital nerve chronic constriction injury.

BACKGROUND: To identify differences in allodynia and grooming behaviours between rat models of either repeated dural nociception with inflammatory soup (IS) or infraorbital nerve chronic constriction injury (IoN-CCI). METHODS: Repeated dural nociception was induced via the application of IS to the dural meninges and IoN-CCI was applied to model neuropathic pain. All surgeries were performed on the right side and a sham operation was performed on the control group. Mechanical and thermal withdrawal thresholds were tested on different facial areas and hindpaw during the interictal period and grooming behaviours were recorded. RESULTS: A significant decreases was found in the mechanical withdrawal thresholds of the bilateral vibrissa pad and right periorbital area in both the IS and the IoN-CCI groups, but only in the left periorbital area of the IS group. Hindpaw thermal allodynia was evident only in the IS group. Ipsilateral hindpaw grooming behaviour increased in the IS group and facial grooming behaviour increased in the IoN-CCI group. CONCLUSIONS: Repeated dural nociception induced by IS and IoN-CCI in rats effectively simulated chronic migraine (CM) and trigeminal neuralgia (TN), respectively. The IS group exhibited a wider range of allodynia than the IoN-CCI group, but further studies are necessary to determine underlying mechanisms.