Traumatic brain injury (TBI) is caused by primary and secondary injury mechanisms. TBI induces a certain amount of inflammatory responses and glutamate excitotoxicity that are believed to participate in the pathogenesis of secondary injury. The non‑narcotic anti‑tussive drug dextromethorphan (DM) has been reported to have a high safety profile in humans and its neuroprotective against a variety of disorders, including cerebral ischemia, epilepsy and acute brain injury. However, few studies have explored the underlying mechanisms of the neuroprotective effects of DM in animals in the setting of TBI. The aim of the present study was to investigate the neuroprotective effects of DM on TBI and to determine the underlying mechanisms. Rats were subjected to a controlled cortical impact (CCI) injury and randomly divided into three groups: Sham‑operated, TBI and DM treatment groups. The DM treatment group was administered DM (30 mg/kg of body weight, intraperitoneally) immediately after injury. It was identified that DM treatment following TBI significantly reduced brain edema and neurological deficits, as well as increased neuronal survival. These effects correlated with a decrease of tumor necrosis factor α, interleukin‑1β (IL‑1β) and IL‑6 protein expression and an increase of glutamate/aspartate transporter and glutamate transporter‑1 in the cortex of the brain. These results provided in vivo evidence that DM exerts neuroprotective effects via reducing inflammation and excitotoxicity induced following TBI. The present study has shed light on the potential use of DM as a neuroprotective agent in the treatment of cerebral injuries.
Background Microvascular decompression (MVD) has been widely accepted as a definitive therapy for primary trigeminal neuralgia (TN). However, some patients may not experience relief of TN symptoms following surgery. In this study, the findings of redo MVD are discussed. Methods Between 2015 and 2017, 205 patients with primary TN underwent MVD surgery in Shanghai Tongren Hospital. Among these patients, 187 had immediate complete relief of symptoms, 8 improved apparently, and 10 reported no symptom relief. Of the 10 patients without relief, 6 underwent reoperation within 5 days, 2 underwent reoperation 3 months after the first procedure, and 2 refused to undergo reoperation. Results The symptoms of those patients who received reoperation disappeared immediately after the surgery. In the second operations, new conflict sites at the motor roots were found in five cases. The real offending vessels were the superior cerebellar artery (SCA) or branch of the SCA in seven cases and the petrosal vein in one case. The nerve was not decompressed completely in either of the two cases. At the 12-month follow-up, no recurrence was found. For the other two patients who did not have reoperation, their symptom persisted. Postoperative complications showed no significant differences between the first and second operations. Conclusion Compression of the motor roots might be one of the causes of TN. Thorough exploration of both sensory and motor roots of the trigeminal nerve is essential to performing a successful MVD operation. Early reoperation for resistant TN after MVD does not increase the incidence of complications.
Our objective of this study is to determine the molecular mechanism of MAPKs (mitogen activated protein kinase systems) on TRPV4 (transient receptor potential vanilloid 4)-mediated trigeminal neuralgia (TN). Partial chronic constriction injury of the infraorbital nerve (CCI-ION) ligation model was used in this research. When treated with antagonists of p38, JNK or ERK, the mechanical hyperalgesia threshold, nerve fiber disorder, myelinoclasis, and Schwann cells proliferation could be reversed. RT-PCR (real-time quantitative polymerase chain reaction), Western blot and IHC (immunohistochemistry) showed that TRPV4 mRNA and protein levels, TRPV4-positive cells and small positive neurons decreased remarkably in TN group treated with antagonists of p38, JNK or ERK. ELISA (enzyme-linked immunosorbent assay) was performed to discover inhibition of MAPK pathway can down-regulate the expression of HATs (histone acetyltransferases), and up-regulate the expression of HDACs (histone deacetylases) in TN, thus inhibiting histone acetylation. Finally, Western blot was performed to identify the phosphorylation status of p38, JNK and ERK, finding decreased phosphorylation forms in antagonists treated TN groups compared with TN groups. Based on the above investigation method, on a whole, our study showed that down-regulation of MAPK pathway could alleviate TRPV4-mediated trigeminal neuralgia, via inhibiting the activation of histone acetylation.
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