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High mobility group box 1 (HMGB1) is a classic damage-associated molecular pattern that has an important role in the pathological inflammatory response. In vitro studies have demonstrated that the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is involved in the regulation of HMGB1 expression, mediating the inflammatory response. Therefore, the purpose of the present study was to evaluate JAK2/STAT3 pathway involvement in the subarachnoid hemorrhage (SAH)-dependent regulation of HMGB1, using an in vivo rat model. A SAH model was established by endovascular perforation. Western blotting, immunohistochemistry and immunofluorescence were used to analyze HMGB1 expression after SAH. In addition, the effects of AG490 after SAH on JAK2/STAT3 phosphorylation, HMGB1 expression and brain damage were evaluated. The results of the present study demonstrated that JAK2/STAT3 was significantly phosphorylated (P<0.05) and the total HMGB1 protein level was significantly increased (P<0.05) after SAH. In addition, the cytosolic HMGB1 level after SAH demonstrated an initial increase followed by a decrease to the control level, while the nuclear HMGB1 level after SAH demonstrated the opposite trend, with an initial decrease and subsequent increase. AG490 administration after SAH significantly inhibited JAK2/STAT3 phosphorylation (P<0.05), suppressed the expression and translocation of HMGB1, reduced cortical apoptosis, brain edema and neurological deficits. These results demonstrated the involvement of the JAK2/STAT3 pathway in HMGB1 regulation after SAH. [ABSTRACT FROM AUTHOR]

Objective To investigate the trends of peripheral blood leucocyte counts and MMP-9/TIMP-1 ratio in acute experimental subarachnoid hemorrhage model in rats and their relationship wíth early brain injury. Methods A rat single cisterna magna injection model was used. Leukocytes were counted by blood counting chamber, and MMP-9 and TIMP-1 were measured by ELISA. The dry-wet weight method was used to measure brain water content. The inside diameter was measured on an HE stained basilar artery. Results The brain water content increased significantly at 6 h after subarachnoid hemorrhage and peaked at 24 h, so did the leukocyte count as well as MMP-9 and TIMP-1 contents. Both the leukocyte count and MMP-9/TIMP-1 ratio were related to early brain injury after subarachnoid hemorrhage. Conclusion The leukocyte count and MMP-9/TIMP-1 ratio increase significantly in the early stage of subarachnoid hemorrhage and return to normal after 72 h. The trend is related to early brain injury after subarachnoid hemorrhage. The MMP-9/TIMP-1 ratio may be used as a predictor of the appearance of early brain injury. [ABSTRACT FROM AUTHOR]

Objective To investigate the possible role of canonical trasnient receptor potential channels (TRPCs) in calcium overload of neurons after subarachnoid hemorrhage (SAH) and discuss the mechanism of TRPCs involved in delayed neuronal death (DND) after SAH. Methods Rat models of SAH were established by double-blood injection via the citerna magna. SAH intervention group was established by using SKF96365 intracerebroventricular injection. Intracellular calcium concentration was detected by Fura-2AM. The dynamic expressions of TRPCs in the cortex and basilar artery were determined by Western blot. The mRNA levels of TRPCs in the cortex and basilar artery were determined by RT-PCR. The results were compared with those in DMSO control model group, saline control group and normal group. The apoptosis of cortical neurons was detected by TUNEL. One-way ANOVA was used to compare within each group. Results The protein expressions and mRNA levels of TRPC1 in the cortex and the basilar artery continuourly increased after SAH and reached the peak on day 5 while intracellular calcium concentration and TUNEL-positive cell counts also reached the peak. After injection of SKF96365, a TRPCs blocker, the protein expressions and mRNA levels of TRPC1 were inhibited, intracellular calcium concentration and TUNEL-positive cell counts decreased. Meanwhile, the scores of rat neurological functions were improved. The expressions of TRPC3 in the cortex and the basilar artery showed no significant change. Conclusion TRPC1 induced calcium overload and CVS after SAH are the major causes of delayed neuronal death. Suppressing calcium influx induced by TRPC1 could delay neuronal death and improve neurological functions. [ABSTRACT FROM AUTHOR]

Objective To investigate the activation of necroptosis pathway and explore the role and molecular mechanism of necroptosis in early brain injury after subarachnoid hemorrhage (SAH). Methods Forty adult male SD rats were divided into four groups ( n = 10 in each): sham, SAH, and SAH treatment plus Nec-1 or dimethyl sulfoxide (DMSO) . SAH model was established by endovascular perforation technique. In SAH+Nec-1 and SAH+ DMSO groups, Nec-1 or DMSO was injected intracerebroventsicularly 30 min prior to SAH establishment. Animals were then sacrificed at 24 h after modeling in each group. The neurological severity scores and brain water content were determined; immunohistochemical method was used in detecting the expression of receptor interacting protein 3 (RIP3). Results Neurological dysfunction, the number of necrotic neuronal cells, brain water content and the expression of RIP3 were significantly increased in the brain tissues of SAH rats (P<0.01). Neurological dysfunction, the number of necrotic neuronal cells, brain water content and the expression of RIP3 were significantly reduced after Nec-1 treatment (P<0.01). Conclusion Necroptoiis is activated and involved in the pathophysiological mechanism of early brain injury after SAH. RIP3 may play a crucial role in necroptosis pathway. Inhibiting necroptosis may be of great importance for protecting neuronal cells and reducing edema in early brain injury after SAH. [ABSTRACT FROM AUTHOR]

Objective To investigate changes of AdipoR in the central nervous system and concentration of serum adiponectin after subarachnoid hemorrhage (SAH) in rats. Methods Fifty-four male Sprague-Dawley rats were randomly divided into three groups: normal group (n = 12), sham-operation group(n = 12), and SAH model group (n = 30). An endovascular perforation model was used to induce SAH in the rats. The expression of AdipoR in the central nervous system was detected by Western blot. The concentration of serum adiponectin was detected by ELISA. Results Compared with that in normal group and sham-operation group, the concentration of serum adiponectin was decreased signíficantly at day 1, 2 and 3 after SAH (P<0.05). Compared with that in normal group and sham-operation group, the expression of AdipoR1 in the cerebral cortex and the hippocampus was up-regulated sharply after SAH (P<0.05), but the expression of AdipoR2 did not change significantly (P>0.05). Conclusion Adiponectin may be involved in the pathophysiological process of early brain injury after SAH. The decreased concentration of serum adiponectin and the up-regulation of AdipoR1 expression are both important pathological mechanisms leading to early brain injury after SAH. [ABSTRACT FROM AUTHOR]

Objective To study the role of neuropeptide Y (NPY) in vasospasm after subarachnoid hemorrhage (SAH) in vitro cultured rat cerebral vascular smooth muscle cells (VSMCs) by observing the proliferation and contraction protein expression of VSMCs. Methods Male or female SD rats weighing 150 g were killed by blood loss. After infusion with saline, the circle of Willis artery and its branches were harvested and primary VSMCs were cultured. Then in vitro model of SAH was established by exposure to oxyhemoglobin of 10-6 mol/L. Then the cells were treated with NPY or BIB03304 (a commonly used blocker of NPY receptor), or NPY + BIB03304. After culturing 1,3,5 and 7 days, immunofluorescence was used to measure the expression of α-actin. IPP software was used to measure the fluorescence intenty and SPSS16.0 statistical software was used for data analysis. Results VSMCs were successfully cutured whli digettion method. The fifth generation of visible cells showed a typical "valley-peak"-like growth. In NPY and NPY + SAH groups, 3-day cell intervention significantly increased the fluorescence intensity of α-actin (P<0. 05), while BIBO 3304 treatment reduced the expression of α-actin, the intensity of which was as weak as that of the blank group (P>0.05). Conclusion NPY increases α-actin expression in VSMCs while BIBO 3304 blocks the up-regulation of α-acin by NPY. NPY plays an important role in delayed cerebral vasospasm after SAH. [ABSTRACT FROM AUTHOR]

Objective To explore the dynamic expression of high mobicity group protein B1(HMGB1) in rats brain tissue after subarachnoid hemorrhage (SAH) and its significance. Methods Rats SAH models were established by perforation of anterior cerebral artery, and randomly divided into 5 subgroups (control group, 6 h, 1, 3, 7 d). ELISA was used to determine the plasm HMGB1 levels after SAH; immunohistochemical staining and western blot were used to survey the dynamic expression of HMGB1 in brain tissue after SAH. Results Plasm HMGB1 levels significantly increased after SAH, and continued to rise from 6 hto 7 d. Immunohistochemical staining indicated that HMGB1 positive cells significantly decreased within the brain tissue in early stage (6 h, 1 d) after SAH, in late stage (3, 7 d) it began to rise and translocated to cytoplasm; Western blot results also showed the expression of HMGB1 decreased first and then increased in the frontal lobe cortex after SAH. Conclusion HMGB1 expression significantly increased not only in brain tissue but also in plasma. HMGB1 may play a important role in inflammatory brain damage after SAH. [ABSTRACT FROM AUTHOR]

Background: A direct aspiration first pass technique (ADAPT) has emerged as a fast, safe, and efficacious method for treating acute large vessel occlusion. However, successful clot aspiration is not guaranteed in every ADAPT procedure. We have observed that when the catheter effectively ingested the clot, the catheter tip displayed a distinct fluttering motion, referred to herein as tip flutter. Thus this study aimed to assess whether this catheter tip flutter can be used as a sign of successful clot aspiration., Methods: This retrospective study included 231 consecutive patients admitted to our institution due to acute ischemic stroke and treated with ADAPT between October 2018 and November 2023. We obtained baseline and procedural data from all patients. Additionally, we assessed the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of the tip flutter in predicting clot aspiration., Results: The incidence of embolus translocation was significantly higher in the tip flutter positive group than in the tip flutter negative group (P < 0.001). Also, hyperdense artery presentation was more prevalent in the positive group (P<0.001), whereas the clot burden score was higher in the negative group (P=0.002). Clot aspiration in the first pass occurred in 83 (96.5%) and 37 (25.5%) patients in the positive and negative groups, respectively (P<0.001). Multivariable logistic regression analysis showed the tip flutter sign (OR 1.09, 95% CI 0.16 to 1.29; P<0.001) was an independent predictor of successful clot aspiration. Sensitivity, specificity, PPV, NPV, and accuracy of the tip flutter for predicting clot aspiration were 69.2%, 97.3%, 96.5 %, 74.5%, and 82.7%, respectively., Conclusions: In this study, we found that tip flutter was a reliable indicator of successful clot aspiration during ADAPT., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Tortuosity of the carotid artery is a common angiographic finding that may impact blood flow and neuronal function. However, information on its prevalence and risk factors remains limited. In this study, we determined to explore the factors affecting carotid artery tortuosity., Methods: The head and neck computed tomography angiography (CTA) imaging and cerebral angiography data performed at the Second Affiliated Hospital of Wenzhou Medical University between January 2019 and September 2021 were collected, and a total of 356 cases were enrolled in the study after screening. Carotid artery tortuosity refers to the angle between the two adjacent segments of the carotid artery, from the opening of the aortic arch on either side to the external orifice of the carotid canal, being less than 150°. A retrospective analysis was performed to compare the general information, laboratory indicators, personal history, and medical history between the two groups. The χ 2 test, t -test, and Mann-Whitney U -test were performed to compare the parameters between the two groups. If there were significant differences between the groups, multivariate logistic regression was performed to analyze the factors affecting carotid artery tortuosity., Results: A total of 222 of the 356 cases were determined to have carotid artery tortuosity, accounting for 63.6%. There were statistically significant differences in age, body mass index (BMI), duration of diabetes and hypertension, levels of low-density lipoprotein cholesterol (LDL-C), diastolic blood pressure, history of ischemic and hemorrhagic stroke, and the usage of antihypertensive drugs between the two groups. Multivariate logistic regression analysis of the above factors showed that age (OR = 5.063, 95% CI 2.963-10.26, p  < 0.001) and duration of hypertension (OR = 2.356, 95% CI 1.353-8.625, p  = 0.021) were associated with a higher incidence of carotid artery tortuosity. Compared to patients who did not consume antihypertensive drugs, the incidence of carotid artery tortuosity was significantly less (OR = 0.094, 95% CI 0.002-0.713, p  = 0.019) in those consuming antihypertensive drugs., Conclusion: Carotid artery tortuosity is a relatively common carotid artery disease. The incidence of carotid artery tortuosity may increase with age and the duration of hypertension. The consumption of antihypertensive drugs may reduce the incidence of carotid artery tortuosity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Huang, Fu, Yao, Wang, Wang, Guo, Li, Chen and Li.)

Rosiglitazone up-regulates caveolin-1 levels and has neuroprotective effects in both chronic and acute brain injury. Therefore, we postulated that rosiglitazone may ameliorate diffuse axonal injury via its ability to up-regulate caveolin-1, inhibit expression of amyloid-beta precursor protein, and reduce the loss and abnormal phosphorylation of tau. In the present study, intraperitoneal injection of rosiglitazone significantly reduced the levels of amyloid-beta precursor protein and hyperphosphorylated tau (phosphorylated at Ser(404)(p-tau (S(404))), and it increased the expression of total tau and caveolin-1 in the rat cortex. Our results show that rosiglitazone inhibits the expression of amyloid-beta precursor protein and lowers p-tau (S(404)) levels, and it reduces the loss of total tau, possibly by up-regulating caveolin-1. These actions of rosiglitazone may underlie its neuroprotective effects in the treatment of diffuse axonal injury.