Elucidating the molecular mechanisms behind the therapeutic impact of median nerve stimulation on cognitive dysfunction post-traumatic brain injury.

OBJECTIVE: Ferroptosis represents a form of regulated cellular death dependent upon iron and lipid peroxidation derivatives, holding considerable implications for cerebral and neurologic pathologies. In the present study, we endeavored to elucidate the molecular mechanisms governing ferroptosis and appraise the therapeutic value of electrical stimulation of median nerve in addressing cognitive impairments following traumatic brain injury (TBI), employing a rodent model. METHODS: In this study, we established a rat model to investigate the cognitive impairments resulting from TBI, followed by the application of median nerve stimulation (MNS). Initially, rats received an intraperitoneal injection of Erastin (2 mg/kg) prior to undergoing MNS. After 24 h of MNS treatment, the rats were subjected to an open field test to evaluate their cognitive and motor functions. Subsequently, we conducted biochemical assays to measure the serum levels of GSH, MDA and SOD. The structural integrity and cellular morphology of hippocampal tissue were examined through H&E staining, Nissl staining and transmission electron microscopy. Additionally, we assessed the expression levels of proteins crucial for neuronal health and function in the hippocampus, including VEGF, SLC7A11, GPX4, Nrf2, α-syn, NEUN and PSD95. RESULTS: Compared to the control group, rats in the stimulation group demonstrated enhanced mobility, reduced levels of tissue damage, a decrease in MDA concentration, and increased levels of GSH and SOD. Additionally, there was a significant upregulation in the expression of proteins critical for cellular defense and neuronal health, including GPX4, SLC7A11, Nrf2, VEGF, α-syn, NEUN, and PSD95 proteins. Conversely, rats in the Erastin group demonstrated decreased mobility, exacerbated pathological tissue damage, elevated MDA concentration, and decreased levels of GSH and SOD. There was also a notable decrease in the expression of GPX4, SLC7CA11, Nrf2, and VEGF proteins. The expression levels of α-syn, NEUN, and PSD95 were similarly diminished in the Erastin group. Each of these findings was statistically significant, indicating that MNS exerts neuroprotective effect in the hippocampal tissue of rats with TBI by inhibiting the ferroptosis pathway. CONCLUSION: (1) MNS may enhance the cognitive and behavioral performance of rats after TBI; (2) MNS can play a neuroprotective role by promoting the expression of nerve injury-related proteins, alleviating oxidative stress and ferroptosis process; (3) MNS may inhibit ferroptosis of neuronal cells by activating Nrf2/ GPX4 signaling pathway, thereby improving cognitive impairment in TBI rats.

Surface Electromyography of Pharyngeal Swallowing in Healthy Chinese Individuals: Establishment of a Timing and Amplitude Database.

This study determined the surface electromyography (sEMG) characteristics of healthy Chinese adults during swallowing to provide a reference for the clinical differential diagnosis of swallowing and dysphagia. sEMG was performed on 187 healthy adults to obtain quantitative information on normal pharyngeal swallowing. The evaluated parameters included the timing and amplitude of sEMG activity in the submental and infrahyoid muscles. A normative database was constructed for the timing and amplitude of muscle activity during pharyngeal swallowing. Results indicated that the duration of sEMG activity was related to the age of the patient; the duration gradually increasing with age. Similarly, the duration of the sEMG activity was associated with the type of swallowing. The duration of the sEMG activity was similar for dry and wet swallowing but was significantly different for excessive swallowing. The mean amplitude of sEMG activity for the submental and infrahyoid muscles was not significantly associated with patient age. A significant correlation between the mean amplitude of sEMG activity and the types of normal swallowing was observed in infrahyoid, but not in submental muscle activity. This study is the first report on the establishment of a normative database for the duration and amplitude of muscle activity based on sEMG analysis of pharyngeal swallowing in healthy Chinese adults.

Enriched environment promotes post-stroke angiogenesis through astrocytic interleukin-17A.

Objective: Our previous studies have revealed that the protective effect of an enriched environment (EE) may be linked with astrocyte proliferation and angiogenesis. However, the relationship between astrocytes and angiogenesis under EE conditions still requires further study. The current research examined the neuroprotective effects of EE on angiogenesis in an astrocytic interleukin-17A (IL-17A)-dependent manner following cerebral ischemia/reperfusion (I/R) injury. Methods: A rat model of ischemic stroke based on middle cerebral artery occlusion (MCAO) for 120 min followed by reperfusion was established, after which rats were housed in either EE or standard conditions. A set of behavior tests were conducted, including the modified neurological severity scores (mNSS) and the rotarod test. The infarct volume was evaluated by means of 2,3,5-Triphenyl tetrazolium chloride (TTC) staining. To evaluate the levels of angiogenesis, the protein levels of CD34 were examined by means of immunofluorescence and western blotting, while the protein and mRNA levels of IL-17A, vascular endothelial growth factor (VEGF), and the angiogenesis-associated factors interleukin-6 (IL-6), JAK2, and STAT3 were detected by western blotting and real-time quantitative PCR (RT-qPCR). Results: We found that EE promoted functional recovery, reduced infarct volume, and enhanced angiogenesis compared to rats in standard conditions. IL-17A expression in astrocytes was also increased in EE rats. EE treatment increased the levels of microvascular density (MVD) and promoted the expression of CD34, VEGF, IL-6, JAK2, and STAT3 in the penumbra, while the intracerebroventricular injection of the IL-17A-neutralizing antibody in EE rats attenuated EE-mediated functional recovery and angiogenesis. Conclusion: Our findings revealed a possible neuroprotective mechanism of astrocytic IL-17A in EE-mediated angiogenesis and functional recovery after I/R injury, which might provide the theoretical basis for EE in clinical practise for stroke patients and open up new ideas for the research on the neural repair mechanism mediated by IL-17A in the recovery phase of stroke.

Serum adiponectin levels are reduced in autism spectrum disorder and association with severity of symptoms.

Recent evidence highlights the role of adiponectin in the pathophysiology of autism spectrum disorder (ASD), yielding conflicting results. The aims of this study were (1) To assess the adiponectin levels of children with ASD and typical developing (TP); (2) To investigate the relationship between adiponectin levels and symptom severity of children with ASD. This is a single-center cross-sectional study from China. From December 2017 to November 2019, first-diagnosis and drug-naïve children with ASD were included. Same TP children who were matched with clinical groups by gender and age were included as the control group. The enzyme-linked immunosorbent assay (ELISA) kit was used to determine serum concentrations of adiponectin. We recorded 176 children (88 were ASD and 88 were TP children) and 77.3% (n = 136) were boys and the mean age was 4.3 years (standard deviations [S.D.]: 1.2). The mean (S.D.) levels of adiponectin were 9.01(2.19) and 11.55(2.32) µg/ml for those with ASD and TP subjects. The difference between those two groups was significant (t = 7.169, p < 0.001). There was a negative correlation between serum levels of adiponectin and Childhood Autism Rating Scale [CARS] score (r = -0.498, p < 0.001). At admission, 39 ASD (54.5%) had a minor autism (CARS<37). In these children, the mean (S.D.) adiponectin level was higher than that observed in children with moderate-to-severe clinical severity (10.09[2.32] vs.8.15[1.64] µg/ml, P < 0.001). This study shows that serum adiponectin. Levels are decreased in ASD when compared with in healthy children. The findings also indicate an inverse association between serum adiponectin levels and severity of symptoms in ASD.

Resuscitation therapy for traumatic brain injury-induced coma in rats: mechanisms of median nerve electrical stimulation.

In this study, rats were put into traumatic brain injury-induced coma and treated with median nerve electrical stimulation. We explored the wake-promoting effect, and possible mechanisms, of median nerve electrical stimulation. Electrical stimulation upregulated the expression levels of orexin-A and its receptor OX1R in the rat prefrontal cortex. Orexin-A expression gradually increased with increasing stimulation, while OX1R expression reached a peak at 12 hours and then decreased. In addition, after the OX1R antagonist, SB334867, was injected into the brain of rats after traumatic brain injury, fewer rats were restored to consciousness, and orexin-A and OXIR expression in the prefrontal cortex was downregulated. Our findings indicate that median nerve electrical stimulation induced an up-regulation of orexin-A and OX1R expression in the prefrontal cortex of traumatic brain injury-induced coma rats, which may be a potential mechanism involved in the wake-promoting effects of median nerve electrical stimulation.

Wake-promoting actions of median nerve stimulation in TBI-induced coma: An investigation of orexin-A and orexin receptor 1 in the hypothalamic region.

A coma is a serious complication, which can occur following traumatic brain injury (TBI), for which no effective treatment has been established. Previous studies have suggested that neural electrical stimulation, including median nerve stimulation (MNS), may be an effective method for treating patients in a coma, and orexin­A, an excitatory hypothalamic neuropeptide, may be involved in wakefulness. However, the exact mechanisms underlying this involvement remain to be elucidated. The present study aimed to examine the arousal­promoting role of MNS in rats in a TBI­induced coma and to investigate the potential mechanisms involved. A total of 90 rats were divided into three groups, comprising a control group, sham­stimulated (TBI) group and a stimulated (TBI + MNS) group. MNS was performed on the animals, which were in a TBI­induced comatose state. Changes in the behavior of the rats were observed following MNS. Subsequently, hypothalamic tissues were extracted from the rats 6, 12 and 24 h following TBI or MNS, respectively. The expression levels of orexin­A and orexin receptor­1 (OX1R) in the hypothalamus were examined using immunohistochemistry, western blotting and an enzyme­linked immunosorbent assay. The results demonstrated that 21 rats subjected to TBI­induced coma exhibited a restored righting reflex and response to pain stimuli following MNS. In addition, ignificant differences in the expression levels of orexin­A and OXIR were observed among the three groups and among the time­points. Orexin­A and OX1R were upregulated following MNS. The rats in the stimulated group reacted to the MNS and exhibited a re­awakening response. The results of the present study indicated that MNS may be a therapeutic option for TBI­induced coma. The mechanism may be associated with increasing expression levels of the excitatory hypothalamic neuropeptide, orexin-A, and its receptor, OX1R, in the hypothalamic region.