Background: Central sensitization is an important pathophysiological mechanism of chronic migraine (CM). According to our previous studies, microglial activation and subsequent inflammation in the trigeminal nucleus caudalis (TNC) contribute to the central sensitization. The P2X7 receptor (P2X7R) is a purinergic receptor expressed in microglia and participates in central sensitization in chronic pain, but its role in CM is unclear. Numerous studies have shown that P2X7R regulates the level of autophagy and that autophagy affects the microglial activation and inflammation. Recently, autophagy has been shown to be involved in neuropathic pain, but there is no information about autophagy in CM. Therefore, the current study investigated the role of P2X7R in CM and its underlying mechanism, focusing on autophagy regulation.Methods: The CM model was established by repeated intraperitoneal injection of nitroglycerin (NTG) in mice. A Von Frey filament and radiant heat were used to assess the mechanical and thermal hypersensitivity. Western blotting and immunofluorescence assays were performed to detect the expression of P2X7R, autophagy-related proteins, and the cellular localization of P2X7R. To determine the role of P2X7R and autophagy in CM, we detected the effects of the autophagy inducer, rapamycin (RAPA) and P2X7R antagonist, Brilliant Blue G (BBG), on pain behavior and the expression of calcitonin gene-related peptide (CGRP) and c-fos. In addition, the effect of RAPA and BBG on microglial activation and subsequent inflammation were investigated.Results: The expression of P2X7R was increased and was mainly colocalized with microglia in the TNC following recurrent NTG administration. The autophagic flux was blocked in CM, which was characterized by up-regulated LC3-II, and accumulated autophagy substrate protein, p62. RAPA significantly improved the basal rather than acute hyperalgesia. BBG alleviated both basal and acute hyperalgesia. BBG activated the level of autophagic flux. RAPA and BBG inhibited the activation of microglia, limited the inflammatory response, and reduced the expression of CGRP and c-fos. Conclusions: Our results demonstrate the dysfunction of the autophagic process in CM. Activated autophagy may have a preventive effect on migraine chronification. P2X7R contributes to central sensitization through mediating autophagy regulation and might become a potential target for CM.
Background: Central sensitization is an important pathophysiological mechanism of chronic migraine (CM). According to our previous studies, microglial activation and subsequent inflammation in the trigeminal nucleus caudalis (TNC) contribute to the central sensitization. The P2X7 receptor (P2X7R) is a purinergic receptor expressed in microglia and participates in central sensitization in chronic pain, but its role in CM is unclear. Numerous studies have shown that P2X7R regulates the level of autophagy and that autophagy affects the microglial activation and inflammation. Recently, autophagy has been shown to be involved in neuropathic pain, but there is no information about autophagy in CM. Therefore, the current study investigated the role of P2X7R in CM and its underlying mechanism, focusing on autophagy regulation.Methods: The CM model was established by repeated intraperitoneal injection of nitroglycerin (NTG) in mice. A Von Frey filament and radiant heat were used to assess the mechanical and thermal hypersensitivity. Western blotting and immunofluorescence assays were performed to detect the expression of P2X7R, autophagy-related proteins, and the cellular localization of P2X7R. To determine the role of P2X7R and autophagy in CM, we detected the effects of the autophagy inducer, rapamycin (RAPA) and P2X7R antagonist, Brilliant Blue G (BBG), on pain behavior and the expression of calcitonin gene-related peptide (CGRP) and c-fos. In addition, the effect of RAPA and BBG on microglial activation and subsequent inflammation were investigated.Results: The expression of P2X7R was increased and was mainly colocalized with microglia in the TNC following recurrent NTG administration. The autophagic flux was blocked in CM, which was characterized by up-regulated LC3-II, and accumulated autophagy substrate protein, p62. RAPA significantly improved the basal rather than acute hyperalgesia. BBG alleviated both basal and acute hyperalgesia. BBG activated the level of autophagic flux. RAPA and BBG inhibited the activation of microglia, limited the inflammatory response, and reduced the expression of CGRP and c-fos. Conclusions: Our results demonstrate the dysfunction of the autophagic process in CM. Activated autophagy may have a preventive effect on migraine chronification. P2X7R contributes to central sensitization through mediating autophagy regulation and might become a potential target for CM.
Objective: Patients who undergo microvascular decompression (MVD) often experience post-craniotomy headache (PCH), while the PCH is always neglected. This study is aimed to describe the natural course and risk factors of PCH. Methods The severity and duration of PCH in 87 patients who undergo MVD were recorded. Factors related to the severity and duration of PCH were analyzed. Results Most patients (63.2%) had at least one assessment of moderate to severe PCH. Almost all patients (92%) would gradually decrease to disappear within 7 days. A small number of patients (25.5%) had PCH at the incision, and other patients had PCH inside the head. Younger age and gas in the prepontine cistern were the salient features of patients in the severe group. Younger, higher SAS, gas in the prepontine cistern area, and postoperative fever were independent risk factors that affect the duration of PCH. Conclusions PCH is the most common and self-limiting complication after MVD among patients with HFS. Young age, temperature > 38˚C after MVD within 24h, and gas around the TN are associated may predict the severity and duration of PCH. Significance This is the first study to describe the severity, duration, location, and risk factors of PCH.
Background: A cortical electroencephalogram (ECoG) is often used for the intraoperative monitoring of epilepsy surgery, and propofol is an important intravenous anesthetic, but its effect on EEGs is unclear. Objectives: To further clarify the effect of propofol on cortical ECoGs during glioma-related epilepsy surgery and to clarify the possible clinical value. Methods: A total of 306 patients with glioma were included in the study. Two hundred thirty-nine with glioma-related epilepsy were included in the epilepsy group, and 67 without glioma-related epilepsy were included in the control group. All patients experienced continuous, real-time ECoG monitoring and long-term follow-up after surgery. Results: After injection of low-dose propofol, the rate of activated ECoGs in the epilepsy group (74%) was significantly higher than in the control group (9%). Furthermore, compared with patients in the untreated group, patients in the treated group had lower rates of early and long-term postoperative seizure frequencies and fewer interictal epileptiform discharges (IEDs). Conclusions: Low-dose infusion of propofol can specifically activate ECoGs in epilepsy patients. Therefore, activated ECoGs might provide an accurate and reliable method for identifying potential epileptic zones during glioma-related epilepsy surgery, resulting in better early and long-term prognoses after epilepsy surgery.
Background: Anterior communicating artery (AcomA) aneurysm is the most common intracranial aneurysm (IA) and has the highest rupture rate. Previously, the preferred surgical treatment for intracranial aneurysms was microsurgery clipping (MC). With the gradual maturation of endovascular treatment (EVT), an increasing number of patients are inclined to treat IA with EVT. In recent years, an increasing number of scholars have suggested that the preferred treatment for wide-necked aneurysms is stent-assisted coiling (SAC). Currently, there are few studies on comparative analyses of the procedural results of SAC in AcomA aneurysms.Methods: We retrospectively reviewed all consecutively treated patients who received SAC for AcomA aneurysms between 12 February 2013, and 20 January 2021. The primary procedural outcome was the occlusion rate evaluated with the Raymond–Roy occlusion classification (RROC) assessed on DSA at follow-up. Safety assessment included 1) ischemic complications (asymptomatic ischemia; intrastent thrombosis; coils falling off plug; arterial dissection); 2) bleeding complications (SAH; ICH); and 3) death. Univariate and multivariate logistic regression analyses were performed to determine patient baseline and aneurysm characteristics associated with total aneurysm occlusion at follow-up. Hemodynamic analysis was performed in one representative case each of the four stents, and six hemodynamic parameters were chosen, including wall shear stress (WSS), cavity blood flow velocity (CBFV), residual blood in the aneurysm (RBA), neck blood flow velocity (NBFV), blood flow inflow (BFI); and inflow concentration index (ICI).Results: A total of 154 patients who underwent EVT via SAC were enrolled for comparative analysis of procedural outcomes. The median age was 55 years, and 56.49% (87) were female. At the first (6–10 months), second (12–15 months) and last (24–48 months) follow-up, complete aneurysm occlusion was observed in 94.8%, 94.8%and 94.2% of patients, respectively. There were no differences regarding the occlusion rates stratified by stent. Each stent showed a variable decrease in all hemodynamic parameters.Conclusion: Hemodynamic parameters all decreased significantly after SAC with all four different stents, and the effect of laser-cut stents on the hemodynamic decline of aneurysms appeared to be more significant than that of woven stents. No significant difference was observed in the follow-up RROC grade among the four stents.
To investigated the antitumor effect of on renal clear cell carcinoma (ccRCC). Network Pharmacology analysis of targets and molecular mechanisms of Alpinetin treating ccRCC. The Annexin V PE/7-AAD kit was used to detect apoptosis. Flow cytometry and Cell Counting Kit-8 (CCK-8) were used to detect cell proliferation and cycle. Cell migration analysis was performed by a 24-well transwell chamber and the ibidi scratch insert. The protein expression of the target molecule was detected by Western blotting. Nude mouse tumorigenesis assays were used to determine the in vivo antitumor effects of alpinetin. Network pharmacology revealed that GAPDH, HRAS, SRC, EGFR, and AKT1 are the main targets of alpinetin for the treatment of ccRCC, with the PIK/AKT signaling pathway being the main pathway of action. Alpinetin could significantly inhibit the proliferation and migration of ccRCC cells by inducing apoptosis. Alpinetin also inhibited the cycle progression of ccRCC cells by blocking them in the G1 phase. Furthermore, in vivo and in vitro, alpinetin could inhibit the activation of PI3K/Akt pathway involved in the proliferation and migration of ccRCC. Alpinetin can inhibit the growth of ccRCC cells by inhibiting the activation of PI3K/Akt pathway and can be a potential anti-cancer drug for ccRCC.
Background: Alpinetin, a natural flavonoid, has been shown to have anticancer effects on many tumors. This study investigated the antitumor effect of alpinetin on renal clear cell carcinoma (ccRCC). Methods: Network Pharmacology analysis was carried out on the targets and molecular mechanisms of alpinetin treating ccRCC. The Annexin V PE/7-AAD kit was used to detect apoptosis. Flow cytometry and Cell Counting Kit-8 (CCK-8) were used to detect cell proliferation and cycle. A 24-well transwell chamber and the ibidi scratch insertion performed cell migration analysis. The protein expression of the target molecule was detected by Western blotting. Nude mouse tumorigenesis assays were used to determine the in vivo antitumor effects of alpinetin. Results: The network pharmacology revealed that GAPDH, HRAS, SRC, EGFR, and AKT1 are the main targets of alpinetin in treating ccRCC, with the PI3K/AKT signaling pathway being the main pathway of action. We found that alpinetin could significantly inhibit the proliferation and migration of ccRCC cells by inducing apoptosis. In addition, alpinetin also inhibited the cycle progression of ccRCC cells by blocking them in the G1 phase. Furthermore, in vivo and in vitro, alpinetin could inhibit the activation of an important pathway involved in the proliferation and migration of ccRCC cells, namely the PI3K/Akt pathway. Conclusion: Alpinetin can inhibit the growth of ccRCC cells by inhibiting the activation of the PI3K/Akt pathway and can be a potential anti-cancer drug for ccRCC.
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