An injectable refrigerated hydrogel for inducing local hypothermia and neuroprotection against traumatic brain injury in mice.

BACKGROUND: Hypothermia is a promising therapy for traumatic brain injury (TBI) in the clinic. However, the neuroprotective outcomes of hypothermia-treated TBI patients in clinical studies are inconsistent due to several severe side effects. Here, an injectable refrigerated hydrogel was designed to deliver 3-iodothyronamine (T1AM) to achieve a longer period of local hypothermia for TBI treatment. Hydrogel has four advantages: (1) It can be injected into injured sites after TBI, where it forms a hydrogel and avoids the side effects of whole-body cooling. (2) Hydrogels can biodegrade and be used for controlled drug release. (3) Released T1AM can induce hypothermia. (4) This hydrogel has increased medical value given its simple operation and ability to achieve timely treatment. METHODS: Pol/T hydrogels were prepared by a low-temperature mixing method and characterized. The effect of the Pol/T hydrogel on traumatic brain injury in mice was studied. The degradation of the hydrogel at the body level was observed with a small animal imager. Brain temperature and body temperature were measured by brain thermometer and body thermometer, respectively. The apoptosis of peripheral nerve cells was detected by immunohistochemical staining. The protective effect of the hydrogels on the blood-brain barrier (BBB) after TBI was evaluated by the Evans blue penetration test. The protective effect of hydrogel on brain edema after injury in mice was detected by Magnetic resonance (MR) in small animals. The enzyme linked immunosorbent assay (ELISA) method was used to measure the levels of inflammatory factors. The effects of behavioral tests on the learning ability and exercise ability of mice after injury were evaluated. RESULTS: This hydrogel was able to cool the brain to hypothermia for 12 h while maintaining body temperature within the normal range after TBI in mice. More importantly, hypothermia induced by this hydrogel leads to the maintenance of BBB integrity, the prevention of cell death, the reduction of the inflammatory response and brain edema, and the promotion of functional recovery after TBI in mice. This cooling method could be developed as a new approach for hypothermia treatment in TBI patients. CONCLUSION: Our study showed that injectable and biodegradable frozen Pol/T hydrogels to induce local hypothermia in TBI mice can be used for the treatment of traumatic brain injury.

Trajectory patterns and influencing factors of supportive care needs in stroke patients: A longitudinal study.

AIM: To investigate the trajectory patterns and influencing factors of supportive care needs in stroke patients. DESIGN: A longitudinal study. METHODS: In total, 207 stroke patients who received treatment at the Department of Neurology in a hospital in Xuzhou between July 2022 and July 2023 were recruited using convenience sampling. Questionnaires including supportive care needs, hospital anxiety and depression scale, and the Barthel index were investigated at baseline and at 1, 3, and 6 months. A latent class growth model was applied to identify the supportive care needs trajectories. Multiple logistic regression was used to determine the predictors for membership. This study adheres to STROBE reporting guidelines. RESULTS: Three patterns of supportive care needs trajectories were identified: A high needs slow decline group (20.8%), a medium needs stable group (56.5%) and a medium needs rapid decline group (22.7%). Based on further analysis, the findings indicated that age, education level, monthly income, comorbidity, activities of daily living, anxiety and depression were associated with the trajectory categories of supportive care needs with stroke patients. CONCLUSION: This study demonstrates heterogeneity in changes in supportive care needs among stroke patients. Healthcare providers need to consider these different categories of needs and develop individualized care measures based on the characteristics of different patients. IMPACT: Healthcare providers should be aware of the fluctuations in care needs of stroke patients at various stages. Additionally, the study aimed to identify patients' specific needs based on their circumstances, monitor the rehabilitation process and establish a more personalized and optimized care plan through multidisciplinary collaboration. The ultimate goal was to alleviate symptomatic distress and address the long-term care needs of patients. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Early activation of Toll-like receptor-3 reduces the pathological progression of Alzheimer's disease in APP/PS1 mouse.

BACKGROUND: Toll-like receptor 3 (TLR3) plays an important role in the immune/inflammatory response in the nervous system and is a main pathological feature of Alzheimer's disease (AD). This study investigates the role of early activation of TLR3 in the pathophysiological process of AD. METHODS: In the experiment, the agonist of TLR3, Poly(I:C), was intraperitoneally injected into the APP/PS1 mouse model of AD and wild-type control mice starting from the age of 4 to 9 months. At the age of 14 months, behavioral tests were conducted. Western blot and immunohistochemistry staining were used to evaluate the level of amyloid ß-protein (Aß), the activation of inflammatory cells, and neuron loss. In addition, the levels of inflammatory cytokines were measured using a quantitative polymerase chain reaction. RESULTS: The results demonstrated that the early activation of TLR3 attenuated neuronal loss and neurobehavioral dysfunction. Moreover, the early activation of TLR3 reduced Aß deposition, inhibited the activation of microglia and astrocytes, and decreased the transcription of pro-inflammatory factors in the hippocampus. CONCLUSIONS: The results indicated that the activation of TLR3 by Poly (I:C) in the early stage of development of AD in a mouse model attenuated neuron loss and improved neurobehavioral functions. The underlying mechanisms could be attributed to its role in Aß clearance, the inhibition of glial cells, and the regulation of neuroinflammation in the hippocampus.

Gain-of-function of progesterone receptor membrane component 2 ameliorates ischemic brain injury.

OBJECTIVE: Progesterone receptor membrane component 2 (PGRMC2) belongs to the membrane-associated progesterone receptor family, which regulates multiple pathophysiological processes. However, the role of PGRMC2 in ischemic stroke remains unexplored. The present study sought to determine the regulatory role of PGRMC2 in ischemic stroke. METHODS: Male C57BL/6J mice were subjected to middle cerebral artery occlusion (MCAO). The protein expression level and localization of PGRMC2 were examined by western blotting and immunofluorescence staining. The gain-of-function ligand of PGRMC2 (CPAG-1, 45 mg/kg) was intraperitoneally injected into sham/MCAO mice, and brain infarction, blood-brain barrier (BBB) leakage, and sensorimotor functions were evaluated by magnetic resonance imaging, brain water content, Evans blue extravasation, immunofluorescence staining, and neurobehavioral tests. The astrocyte and microglial activation, neuronal functions, and gene expression profiles were revealed by RNA sequencing, qPCR, western blotting, and immunofluorescence staining after surgery and CPAG-1 treatment. RESULTS: Progesterone receptor membrane component 2 was elevated in different brain cells after ischemic stroke. Intraperitoneal delivery of CPAG-1 reduced infarct size, brain edema, BBB leakage, astrocyte and microglial activation, and neuronal death, and improved sensorimotor deficits after ischemic stroke. CONCLUSION: CPAG-1 acts as a novel neuroprotective compound that could reduce neuropathologic damage and improve functional recovery after ischemic stroke.

Circ_0003159 upregulates LIFR expression through competitively binding to miR-221-3p/miR-222-3p to block gastric cancer development.

Gastric cancer (GC) remains a major cause of cancer-related deaths. Increasing studies suggest that cancer development is accompanied by the deregulation of circular RNAs. We investigated the function of circ_0003159 in GC. The expression levels of circ_0003159, miR-221-3p/miR-222-3p and leukemia inhibitory factor receptor (LIFR) mRNA were measured by real-time quantitative polymerase chain reaction. Cell colony formation ability was assessed by colony formation assay, and cell viability was assessed by cell counting kit-8 assay. Cell apoptosis was assessed by flow cytometry assay and caspase3 activity. Cell migration and invasion were assessed by transwell assay. Glycolysis energy metabolism was assessed by 5'-triphosphate production, glucose uptake and lactate production. The protein levels of related marker proteins and LIFR were detected by western blot. The relationship between circ_0003159 and miR-221-3p/miR-222-3p, or LIFR and miR-221-3p/miR-222-3p was obtained from bioinformatics tools and verified by dual-luciferase reporter assay. A cancer tumorogenicity xenograft experiment in nude mice was conducted to determine the role of circ_0003159 in tumor growth by AGS cells. Our results showed that circ_0003159 expression was decreased in GC tissues and cells. Circ_0003159 overexpression sequestered GC cell viability, migration, invasion and glycolysis and induced cell apoptosis. MiR-221-3p and miR-222-3p were targets of circ_0003159, and the inhibition of miR-221-3p and miR-222-3p also blocked GC cell viability, migration, invasion and glycolysis and promoted cell apoptosis. LIFR was a common target of miR-221-3p and miR-222-3p. Interestingly, LIFR knockdown reversed the effects of circ_0003159 overexpression on GC cell behaviors. Circ_0003159 increased the expression level of LIFR by targeting miR-221-3p and miR-222-3p. The tumorigenicity assay showed that circ_0003159 overexpression inhibited tumor growth in vivo. In conclusion, circ_0003159 inhibited GC development in vitro and in vivo by enriching the level of LIFR via direct binding to miR-221-3p/miR-222-3p.

Inhibition of progesterone receptor membrane component-1 exacerbates neonatal hypoxic-ischemic cerebral damage in male mice.

This study investigated the expression of progesterone receptor membrane component 1 (pgrmc1) in the brains of male and female mice, and the effect of inhibiting pgrmc1 on neonatal hypoxic-ischemic (HI) cerebral injury in male mice. A mouse model of neonatal HI brain injury was established, and AG205, a specific antagonist of pgrmc1, was injected into the left lateral cerebral ventricle 1 h before HI. Histological staining, behavior testing, Western blots, and quantitative PCR (qPCR) were employed to evaluate pgrmc1 expression, brain damage, neurological function, and molecular mechanisms. Results demonstrated that the mRNA and protein levels of pgrmc1 increased significantly in the cortex and hippocampus 72 h after HI without sex differences. The inhibition of pgrmc1 exacerbated the neonatal brain damage in the acute stage of HI in male mice as seen in the increase in brain water content, infarction area, and neuronal death. Inhibition of pgrmc1 also aggravated the neurological dysfunction and anxiety induced by HI brain injury. In addition, inhibition of pgrmc1 activated the NF-kB signaling and NF-κB-mediated cytokines, and inhibited BDNF/PI3K/AKT pathway in the brains of the newborn HI mice. The results indicated that pgrmc1 inhibition exacerbated the brain damage in newborn male mice subjected to HI by activating IκBα/NFκB signaling and inhibiting BDNF/PI3K/Akt pathway.

Cranial capacity measurement for modern Chinese adults based on 3D reconstruction.

OBJECTIVES: To determine the average modern adult cranial capacity in China, and assess the gender differences and trends in order to establish normal reference values and provide theoretical basis for individualized treatment in clinical practice. METHODS: We conducted a cross-sectional study between January 2019 to June 2020. Thin-slice (0.9 mm) CT scans of 309 males and 238 females from China were obtained, and classified into the 18-32, 33-47, 48-62, 63-77 and 78-92 years age groups. Three-dimensional reconstruction was performed using mimics software to obtain the cranial capacity for statistical analysis. RESULTS: The average cranial capacity of men was 1497.12±120.70 cm3 and that of women was 1326.24±95.72 cm3. The average cranial capacity of men was larger than that of women in all age groups. In addition, cranial capacity across the different age groups showed significant differences among both men and women. CONCLUSION: The average cranial capacity of modern Chinese male is larger that of females, and both sexes show a tendency to an increase in the intracranial volume over the past few decades. Our findings provide important data for establishing normal reference values for cranial capacity of modern Chinese adults and theoretical basis for individualized treatment of certain cranial diseases with increased intracranial pressure.

In Situ implantable, post-trauma microenvironment-responsive, ROS Depletion Hydrogels for the treatment of Traumatic brain injury.

Traumatic brain injury (TBI) generates excess reactive oxygen species (ROS), which can exacerbate secondary injury and result in disability and death. Secondary injury cascades can trigger the release of uncontrolled ROS into the surrounding normal brain tissue, forming an extended pool of ROS, which leads to massive neuronal death. Here, we developed an injectable, post-trauma microenvironment-responsive, ROS depletion hydrogel embedded curcumin (Cur) (TM/PC) for reducing ROS levels in damaged brain tissue to promote the regeneration and recovery of neurons. Hydrogel was composed of three parts: (1) Hydrophobic poly (propylene sulfide)120 (PPS120) was synthesized, with a ROS quencher and H2O2-responsive abilities, to embed Cur. (2) Matrix metalloproteinase (MMP)-responsive triglycerol monostearate (TM) was used to cover the PPS120 to form a TM/P hydrogel. (3) Cur could further eradicate the ROS, promoting the regeneration and recovery of neurons. In two postoperative TBI models, TM/PC hydrogel effectively responded the TBI surgical environment and released drug. TM/PC hydrogel significantly depleted ROS and reduced brain edema. In addition, reactive astrocytes and activated microglia were decreased, growth-associated protein 43 (GAP43) and doublecortin (DCX) were increased, suggested that TM/PC hydrogel had the strongest anti-inflammatory effect and effectively promoted nerve regeneration after TBI. This study provides new information for the management of TBI to prevent the secondary spread of damage.

Artificial neural network predicts hemorrhagic contusions following decompressive craniotomy in traumatic brain injury.

BACKGROUND: This study aimed to explore relevant factors of hemorrhagic contusions following decompressive craniotomy (DC) in traumatic brain injury (TBI) and create an artificial neural network (ANN) prediction model of the risk factors of hemorrhagic contusions. METHODS: This study analyzed 425 patients with TBI who underwent DC in the Neurosurgery Department of Shaoxing People's Hospital between 2009 and 2014. Patients were divided into two groups according to the first postoperative CT scans: hemorrhage group and non-hemorrhage group. Gender, age, preoperative situations (Initial Rotterdam CT Score, GCS Score, pupillary response, laboratory data and preoperative hematoma), the time gap between trauma and DC, postoperative CT scans, and Glasgow Outcome Scale (GOS) scores were recorded. ANN was used to predict hematoma. Correlation analysis was used to state the relationship between increased hemorrhage volumes and GOS scores. RESULTS: The ANN prediction model was established. This model included 11 parameters: initial Rotterdam CT score, GCS score, C-reactive protein, age, the time gap between trauma and DC, pupillary response, platelet count, bone-flap size, glucose level, hernia magnitude and preoperative hematoma volume. The overall predictive accuracy of the model was 73.0%. CONCLUSIONS: Initial Rotterdam CT scores and GCS scores may predict the risk of expansion contusions following DC. The ANN prediction model has a high accuracy to forecast hemorrhage.

Toll-like receptor-2 gene knockout results in neurobehavioral dysfunctions and multiple brain structural and functional abnormalities in mice.

OBJECTIVE: Toll-like receptor-2 (TLR2), a member of TLR family, plays an important role in the induction and regulation of immune/inflammation. TLR2 gene knockout (TLR2KO) mice have been widely used for animal models of neurological diseases. Since there is close relationship between immune system and neurobehavioral functions, it is important to clarify the exact role of TLR2 defect itself in neurobehavioral functions. The present study aimed to investigate the effect of TLR2KO on neurobehavioral functions in mice and the mechanisms underlying the observed changes. METHODS: Male TLR2KO and wild type (WT) mice aged 3, 7, and 12 months were used for neurobehavioral testing and detection of protein expression by Western blot. Brain magnetic resonance imaging (MRI), electrophysiological recording, and Evans blue (EB) assay were applied to evaluate regional cerebral blood flow (rCBF), synaptic function, and blood-brain barrier (BBB) integrity in 12-month-old TLR2KO and age-matched WT mice. RESULTS: Compared to WT mice, TLR2KO mice showed decreased cognitive function and locomotor activity, as well as increased anxiety, which developed from middle age (before 7-month-old) to old age. In addition, significantly reduced regional cerebral blood flow (rCBF), inhibited long-term potentiation (LTP), and increased blood-brain barrier (BBB) permeability were observed in 12-month-old TLR2KO mice. Furthermore, compared with age-matched WT mice, significant reduction in protein levels of tight junction proteins (ZO-1, Occludin, and Claudin-5) and increased neurofilament protein (SMI32) were observed in 7 and 12-month-old TLR2KO mice, and that myelin basic protein (MBP) decreased in 12-month-old TLR2KO mice. CONCLUSION: Our data demonstrated that TLR2 defect resulted in significantly observable neurobehavioral dysfunctions in mice starting from middle age, as well as multiple abnormalities in brain structure, function, and molecular metabolism.

Esophageal Histological Precursor Lesions and Subsequent 8.5-Year Cancer Risk in a Population-Based Prospective Study in China.

INTRODUCTION: Data on the associations between esophageal histological lesions and risk of esophageal squamous cell carcinoma (ESCC) in general populations are limited. We aimed to investigate these associations in a large Chinese general population to inform future Chinese ESCC screening guidelines. METHODS: We performed endoscopic screening of 21,111 participants aged 40-69 years from 3 high-risk areas of China in 2005-2009, and followed the cohort through 2016. Cumulative incidence and mortality rates of ESCC were calculated by baseline histological diagnosis, and hazard ratios of ESCC, overall and by age and sex, were assessed using the Cox proportional hazards models. RESULTS: We identified 143 new ESCC cases (0.68%) and 62 ESCC deaths (0.29%) during a median follow-up of 8.5 years. Increasing grades of squamous dysplasia were associated with the increasing risk of ESCC incidence and mortality. The cumulative ESCC incidence rates for severe dysplasia/carcinoma in situ, moderate dysplasia (MD), and mild dysplasia were 15.5%, 4.5%, and 1.4%, respectively. Older individuals (50-69 years) had 3.1 times higher ESCC incidence than younger individuals (40-49 years), and men had 2.4 times higher ESCC incidence than women. DISCUSSION: This study confirmed that increasing grades of squamous dysplasia are associated with increasing risk of ESCC and that severe dysplasia and carcinoma in situ require clinical treatment. This study suggests that in high-risk areas of China, patients with endoscopically worrisome MD should also receive therapy, the first screening can be postponed to 50 years, and endoscopic surveillance intervals for unremarkable MD and mild dysplasia can be lengthened to 3 and 5 years, respectively.

Genomic deletion of TLR2 induces aggravated white matter damage and deteriorated neurobehavioral functions in mouse models of Alzheimer's disease.

Toll-like receptor-2 (TLR2), a member of the TLR family, plays an important role in the initiation and regulation of immune/inflammation response, which is a critical mechanism underlying Alzheimer's disease (AD). To clarify the role of TLR2 in the pathological process of AD, in the present study, TLR2 knockout plus APPswe/PSEN1dE9 transgenic mice (AD-TLR2KO) were generated. Neurobehavioral tests and brain MRI scan were conducted on mice at the age of 12 months. Additionally, neuron loss was evaluated using NeuN staining. Amyloid ß protein (Aß), glial fibrillary acidic protein (GFAP), endogenous ligands for TLR2, and the activation of downstream signaling of TLR2 in mouse brains were detected by immunohistochemistry and Western blots. The results demonstrated that TLR2 deficit induced learning disabilities, decreased spontaneous activity, increased anxiety and depression, and led to white matter damage (WMD), brain atrophy, loss of neurons, and glial activation. Moreover, TLR2 deficit aggravated impaired neurobehavioral functions and WMD in AD mice, but did not affect the Aß deposition in mouse brains. Our data indicate that the genomic deletion of TLR2 impairs neurobehavioral functions, induces WMD and brain atrophy, and increases the activation of astrocytes, which in turn aggravate the symptoms of AD through a non-Aß mechanism.

3D printing of intracranial aneurysm based on intracranial digital subtraction angiography and its clinical application.

The study aimed to develop simulation models including intracranial aneurysmal and parent vessel geometries, as well as vascular branches, through 3D printing technology. The simulation models focused on the benefits of aneurysmal treatments and clinical education. This prospective study included 13 consecutive patients who suffered from intracranial aneurysms confirmed by digital subtraction angiography (DSA) in the Neurosurgery Department of Shaoxing People's Hospital. The original 3D-DSA image data were extracted through the picture archiving and communication system and imported into Mimics. After reconstructing and transforming to Binary STL format, the simulation models of the hollow vascular tree were printed using 3D devices. The intracranial aneurysm 3D printing simulation model was developed based on DSA to assist neurosurgeons in aneurysmal treatments and residency training. Seven neurosurgical residents and 15 standardization training residents received their simulation model training and gave high assessments for the educational course with the follow-up qualitative questionnaire. 3D printed simulation models based on DSA can perfectly reveal target aneurysms and help neurosurgeons select therapeutic strategies precisely. As an educational tool, the 3D aneurysm vascular simulation model is useful for training residents.

Gender difference in the effect of progesterone on neonatal hypoxic/ischemic brain injury in mouse.

This study investigated the effects of progesterone (PROG) on neonatal hypoxic/ischemic (NHI) brain injury, the differences in effects between genders, and the underlying mechanisms. NHI brain injury was established in both male and female neonatal mice induced by occlusion of the left common carotid artery followed by hypoxia. The mice were treated with PROG or vehicle. Fluoro-Jade B staining (F-JB), long term behavior testing, and brain magnetic resonance image (MRI) were applied to evaluate neuronal death, neurological function, and brain damage. The underlying molecular mechanisms were also investigated by Western blots. The results showed that, in the male mice, administration of PROG significantly reduced neuronal death, improved the learning and memory function impaired by cerebral HI, decreased infarct size, and maintained the thickness of the cortex after cerebral HI. PROG treatment, however, did not show significant neuroprotective effects on female mice subjected to HI. In addition, the data demonstrated a gender difference in the expression of tumor necrosis factor receptor 1 (TNFR1), TNF receptor associated factor 6 (TRAF6), Fas associated protein with death domain (FADD), and TIR-domain-containing adapter-inducing interferon-ß (TRIF) between males and females. Our results indicated that treatment with PROG had beneficial effects on NHI injured brain in acute stage and improved the long term cognitive function impaired by cerebral HI in male mice. In addition, the activation of TNF and TRIF mediated signaling in response to cerebral HI and the treatment of PROG varied between genders, which highly suggested that gender differences should be emphasized in evaluating neonatal HI brain injury and PROG effects, as well as the underlying mechanisms.

The development of CAR design for tumor CAR-T cell therapy.

In recent years, the chimeric antigen receptor modified T cells (Chimeric antigen receptor T cells, CAR-T) immunotherapy has developed rapidly, which has been considered the most promising therapy. Efforts to enhance the efficacy of CAR-based anti-tumor therapy have been made, such as the improvement of structures of CAR-T cells, including the development of extracellular antigen recognition receptors, intracellular co-stimulatory molecules and the combination application of CARs and synthetic small molecules. In addition, effects on the function of the CAR-T cells that the space distance between the antigen binding domains and tumor targets and the length of the spacer domains have are also being investigated. Given the fast-moving nature of this field, it is necessary to make a summary of the development of CAR-T cells. In this review, we mainly focus on the present design strategies of CAR-T cells with the hope that they can provide insights to increase the anti-tumor efficacy and safety.

Morphological Effect on Wall Shear Stress in Intracranial Aneurysms.

BACKGROUND AND STUDY AIMS: Both high and low wall shear stress (WSS) play important roles in the development and rupture of intracranial aneurysms (IAs). This study aimed to determine the morphological factors that affect WSS in the IA and the parent artery. MATERIAL AND METHODS: We studied a total of 66 IAs with three-dimensional imaging. Computational fluid dynamics (CFD) models were constructed and used to characterize the hemodynamics quantitatively. Aneurysms were grouped according to the mean neck width. The associations among hemodynamics and morphology were analyzed. RESULTS: Aspect ratio was correlated to lowest WSS (r = - 0.576), aneurysm-to-parent vessel (A-P) WSS ratio (r = - 0.500), and lowest-parent vessel (L-P) WSS ratio (r = - 0.575). Height-to-width ratio and height were correlated to WSS. Mean aneurysm WSS (p = 0.023), lowest WSS (p < 0.0001), highest-to-lowest WSS ratio (p = 0.004), L-P WSS ratio (p < 0.0001), highest-parent vessel (H-P) WSS ratio (p = 0.008), A-P WSS ratio (p < 0.001), and height (p < 0.001) were different between the two groups of aneurysms that were divided by the relationship between the diameters of the aneurysms and the necks. Multivariable analysis showed that the lowest WSS (p = 0.028) and A-P WSS ratio (p = 0.001) were independently associated with neck width. CONCLUSION: Morphological characteristics are associated with IA and parent vessel WSS. Aneurysms with different neck widths have different hemodynamics. These results could help in understanding the progression of IA and in building predictive models for IA rupture.

Intercorrelations of morphology with hemodynamics in intracranial aneurysms in computational fluid dynamics.

OBJECTIVE: To measure morphological indices and wall shear stress (WSS) of aneurysms and parent artery surface in order to explore the relationship of morphological characteristics and WSS. METHODS: Data from 47 events of consecutive cerebral saccular aneurysms from 39 patients which were referred to the interventional Neuroradiology service of the Shaoxing People`s Hospital, Shaoxing, China between 2014 April and 2015 August. Wall shear stress and wall pressure (WP) of the pre-aneurysm, aneurysm and near vessel (<1.0 cm) surface were obtained. Correlation analysis was carried between morphological parameters and WSS and its ratio. WSS, WP, intra-aneurysmal flow pattern, and location of aneurysms were analyzed. RESULTS: Impaction zone from inflow jet was located in the distal neck part of aneurysm with high WSS in 36 aneurysms (76.6%). There were significant differences in WSS between pre-aneurysm surface and near vessel (p<0.001), aneurysm (p<0.001), aneurysm and near vessel (p<0.001). Significant correlations were found between aneurysm WSS and aspect ratio (r=-0.296), aneurysm-artery WSS ratio and size ratio (r=-0.322), aspect ratio (r=-0.416). CONCLUSION: Uneven WSS distributes in the various part of the pre-aneurysm vessel. The impaction zone from inflow jet is located in the distal neck of aneurysm. Aspect and size ratios can effect aneurysm WSS.

Activated mGluR5 protects BV2 cells against OGD/R induced cytotoxicity by modulating BDNF-TrkB pathway.

Activated Metabotropic glutamate receptors 5(mGluR5) exhibits protective effects against ischemic brain damage, but the underlying mechanisms are not clearly known. Brain-derived neurotrophic factor (BDNF), as a valuable member of neurotrophic factor family, exerts its protection by combining with its high-affinity receptor tyrosine protein kinase B (TrkB). To investigate the role of activated mGluR5 against oxygen-glucose deprivation (OGD)/reoxygenation (R)-mediated cytotoxicity, the cell viability, apoptosis, the release of inflammatory cytokines and accumulation of reactive oxygen species (ROS) were evaluated in BV2 cells (Microglia cell line) with or without OGD/R exposure. Our data show that CHPG (the selective mGluR5 agonist) pretreatment, as an mGluR5 agonist, protected BV2 cells against OGD/R-induced cytotoxicity, apoptosis, the release of inflammatory cytokines, and the accumulation of ROS. However, these effects were significantly reversed by the mGluR5 antagonist MPEP pretreatment. Our data also show that the expressions of BDNF and TrkB were significantly decreased in BV2 cells with OGD/R exposure. CHPG pretreatment significantly enhanced the expressions of BDNF and TrkB in BV2 cells with OGD/R exposure. However, the increased expressions were significantly abrogated by MPEP pretreatment. In addition, inhibition of BDNF/TrKB pathway by K252a also attenuated the protective effects of activated mGluR5 against OGD/R-induced cytotoxicity, apoptosis and the release of inflammatory cytokines. Morever, pretreatment with exogenous BDNF protected BV2 cells against OGD/R induced apoptosis and release of inflammatory cytokines. These data suggested that BDNF/TrKB pathway may be involved in regulating activated mGluR5' protective effects against OGD/R induced cytotoxicity in BV2 cells.

Purinergic 2X7 receptor/NLRP3 pathway triggers neuronal apoptosis after ischemic stroke in the mouse.

Previous research has shown that Purinergic 2X7 receptor (P2X7R) and NLRP3 inflammasome contribute to the inflammatory activation. In this study, we investigated whether P2X7R/NLRP3 pathway is involved in the caspase-3 dependent neuronal apoptosis after ischemic stroke by using a focal cortex ischemic stroke model. The expressions of P2X7R, NLRP3 inflammsome components, and cleaved caspase-3 were significantly enhanced in the ischemic brain tissue after stroke. However, the expression of cleaved caspase-3 was significantly attenuated after treatment of stroke with P2X7R antagonist (BBG) or NLRP3 inhibitor (MCC950). The treatment also significantly reduced the infarction volume, neuronal apoptosis, and neurological impairment. In addition, in vitro data also support the hypothesis that P2X7R/NLRP3 pathway plays a vital role in caspase-3 dependent neuronal apoptosis after ischemic stroke. Further investigation of effective regulation of P2X7R and NLRP3 in stroke is warranted.

Association between hemodynamics, morphology, and rupture risk of intracranial aneurysms: a computational fluid modeling study.

The objective of the study was to examine the correlations between intracranial aneurysm morphology and wall shear stress (WSS) to identify reliable predictors of rupture risk. Seventy-two intracranial aneurysms (41 ruptured and 31 unruptured) from 63 patients were studied retrospectively. All aneurysms were divided into two categories: narrow (aspect ratio ≥1.4) and wide-necked (aspect ratio <1.4 or neck width ≥4 mm). Computational fluid dynamics was used to determine the distribution of WSS, which was analyzed between different morphological groups and between ruptured and unruptured aneurysms. Sections of the walls of clipped aneurysms were stained with hematoxylin-eosin, observed under a microscope, and photographed. Ruptured aneurysms were statistically more likely to have a greater low WSS area ratio (LSAR) (P = 0.001) and higher aneurysms parent WSS ratio (P = 0.026) than unruptured aneurysms. Narrow-necked aneurysms were statistically more likely to have a larger LSAR (P < 0.001) and lower values of MWSS (P < 0.001), mean aneurysm-parent WSS ratio (P < 0.001), HWSS (P = 0.012), and the highest aneurysm-parent WSS ratio (P < 0.001) than wide-necked aneurysms. The aneurysm wall showed two different pathological changes associated with high or low WSS in wide-necked aneurysms. Aneurysm morphology could affect the distribution and magnitude of WSS on the basis of differences in blood flow. Both high and low WSS could contribute to focal wall damage and rupture through different mechanisms associated with each morphological type.