Salvianolic acid B ameliorates neuroinflammation and neuronal injury via blocking NLRP3 inflammasome and promoting SIRT1 in experimental subarachnoid hemorrhage.

The nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated immuno-inflammatory response plays a critical role in exacerbating early brain injury (EBI) after subarachnoid hemorrhage (SAH). Salvianolic acid B (SalB) has previously been shown to suppress neuroinflammatory responses in many disorders. Meanwhile, a previous study has demonstrated that SalB mitigated oxidative damage and neuronal degeneration in a prechiasmatic injection model of SAH. However, the therapeutic potential of SalB on immuno-inflammatory responses after SAH remains unclear. In the present study, we explored the therapeutic effects of SalB on neuroinflammatory responses in an endovascular perforation SAH model. We observed that SalB ameliorated SAH-induced functional deficits. Additionally, SalB significantly mitigated microglial activation, pro-inflammatory cytokines release, and neuronal injury. Mechanistically, SalB inhibited NLRP3 inflammasome activation and increased sirtuin 1 (SIRT1) expression after SAH. Administration of EX527, an inhibitor of SIRT1, abrogated the anti-inflammatory effects of SalB against SAH and further induced NLRP3 inflammasome activation. In contrast, MCC950, a potent and selective NLRP3 inflammasome inhibitor, reversed the detrimental effects of SIRT1 inhibition by EX527 on EBI. These results indicated that SalB effectively repressed neuroinflammatory responses and neuronal damage after SAH. The action of SalB appeared to be mediated by blocking NLRP3 inflammasome and promoting SIRT1 signaling.

The m6A methyltransferase METTL3 promotes LPS-induced microglia inflammation through TRAF6/NF-κB pathway.

OBJECTIVES: Microglia are the main effectors in the inflammatory process of the central nervous system. Once overactivated, microglia may release pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α and IL-18, etc.) and accelerate neurodegeneration. Here, we aimed to explore the mechanism of how m6A methyltransferase METTL3 affects the inflammatory response of microglia, appropriately inhibiting the overactivation of microglia. MATERIALS AND METHODS: Lipopolysaccharide (LPS) was used to construct a cellular inflammation model in vitro. To evaluate the expression of METTL3 and inflammatory cytokines (IL-1ß, IL-6, TNF-α and IL-18) in cells, RT-PCR and ELISA were carried out. The related protein (TRAF6, NF-κB and I-κB) expression was examined adopting Western blot. Dot blot experiment was used to assess the effect of regulating METTL3 on the m6A level. Methylated RNA immunoprecipitation reaction was used to measure the effect of METTL3 on the m6A level of TRAF6 mRNA 3'-UTR. The co-immunoprecipitation experiment (IP) proved that METTL3 combines with TRAF6. RESULTS: In LPS-mediated microglial inflammation, METTL3 expression was increased, and the expression of inflammatory cytokines (IL-1ß, IL-6, TNF-α and IL-18) and inflammatory proteins (TRAF6 and NF-κB) were upregulated. METTL3 level was positively correlated with TRAF6, and the two proteins could bind to each other. Overexpression of METTL3 promoted the activation of the TRAF6-NF-κB pathway in an m6A-dependent manner, and inhibiting NF-κB attenuated METTL3-mediated microglial activation. CONCLUSION: METTL3 promotes LPS-induced microglial inflammation by activating the TRAF6-NF-κB pathway.

SIRT1 Promotes M2 Microglia Polarization via Reducing ROS-Mediated NLRP3 Inflammasome Signaling After Subarachnoid Hemorrhage.

Mounting evidence has suggested that modulating microglia polarization from pro-inflammatory M1 phenotype to anti-inflammatory M2 state might be a potential therapeutic approach in the treatment of subarachnoid hemorrhage (SAH) injury. Our previous study has indicated that sirtuin 1 (SIRT1) could ameliorate early brain injury (EBI) in SAH by reducing oxidative damage and neuroinflammation. However, the effects of SIRT1 on microglial polarization and the underlying molecular mechanisms after SAH have not been fully illustrated. In the present study, we first observed that EX527, a potent selective SIRT1 inhibitor, enhanced microglial M1 polarization and nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation in microglia after SAH. Administration of SRT1720, an agonist of SIRT1, significantly enhanced SIRT1 expression, improved functional recovery, and ameliorated brain edema and neuronal death after SAH. Moreover, SRT1720 modulated the microglia polarization shift from the M1 phenotype and skewed toward the M2 phenotype. Additionally, SRT1720 significantly decreased acetylation of forkhead box protein O1, inhibited the overproduction of reactive oxygen species (ROS) and suppressed NLRP3 inflammasome signaling. In contrast, EX527 abated the upregulation of SIRT1 and reversed the inhibitory effects of SRT1720 on ROS-NLRP3 inflammasome activation and EBI. Similarly, in vitro, SRT1720 suppressed inflammatory response, oxidative damage, and neuronal degeneration, and improved cell viability in neurons and microglia co-culture system. These effects were associated with the suppression of ROS-NLRP3 inflammasome and stimulation of SIRT1 signaling, which could be abated by EX527. Altogether, these findings indicate that SRT1720, an SIRT1 agonist, can ameliorate EBI after SAH by shifting the microglial phenotype toward M2 via modulation of ROS-mediated NLRP3 inflammasome signaling.

Hemodynamic Characteristics Associated with Recurrence of Middle Cerebral Artery Bifurcation Aneurysms After Total Embolization.

OBJECTIVE: Hemodynamic parameters are associated with the recurrence of intracranial aneurysms (IAs). Studies showed that high velocity and wall shear stress (WSS) were associated with IAs recurrence after endovascular treatment; nevertheless, factors such as small sample size, locations of IAs, and types of IAs (ie, sidewall or bifurcation) were neglected. The purpose of this study was to identify the hemodynamic characteristics associated with recurrence of middle cerebral artery bifurcation aneurysms (MCABAs) after total embolization by the method of computer fluid dynamics (CFD). METHODS: Following inclusion criteria, we included 92 MCABAs treated with coils only after total embolization from January 2014 to January 2019. We segmented into recurrent and non-recurrent groups according to follow-up digital subtraction angiography (DSA). The MCABA models, including pre-operatively and immediate post-operatively, were reconstructed using 3D-DSAs. The hemodynamic parameters pre-operatively and immediately post-operatively between the groups were calculated and analyzed. RESULTS: There were no significant differences between the recurrent and non-recurrent groups for spatially averaged wall shear stress (SAWSS), maximum wall shear stress (MWSS), velocity, or oscillatory shear index (OSI) at the neck pre-operatively. In the recurrent group, the WSS (22.02±5.11 vs 37.43±8.27 pa, p < 0.001), MWSS (42.59±17.02 vs 66.98±18.61 pa, p=0.014), velocity (0.86±0.19 vs 1.44±0.61 m/s, p=0.01) preoperatively were significantly higher than postoperative values. By contrast, in the non-recurrent group, the WSS (26.53±8.18 vs 22.29±8.64pa, p=0.002), MWSS (42.71±14.01 vs 37.15±15.56 pa, p=0.013), velocity (1.08±0.43 vs 0.23 (0.52, 0.57) m/s, p < 0.001) postoperatively were significantly lower than preoperative values. The OSI, whether in the recurrent group or the non-recurrent group, did not differ significantly between groups (p=0.79 and p=0.19). CONCLUSION: Higher WSS (SAWSS, MWSS) and flow velocity at the aneurysm neck after embolization might be related to recurrence of bifurcation IAs. These might be applied to clinical post-embolization management for the evaluation of bifurcation IAs recanalization.

Hemodynamic and Morphological Parameters of Ruptured Mirror Posterior Communicating Artery Aneurysms.

Objective: Morphological and hemodynamic parameters might predict rupture of intracranial aneurysms (IAs). A practical model for the study is patients with ruptured mirror IAs in which one is ruptured and the other is unruptured. Although there have been analyses of the morphology and hemodynamics of ruptured mirror posterior communicating artery aneurysms (PComAAs), the sample sizes in these studies were small and only considered hemodynamics or morphological characters. Therefore, this study aimed to investigate the morphological and hemodynamic parameters associated with ruptured mirror PComAAs. Methods: We considered 72 patients with ruptured mirror PComAAs using computational fluid dynamics (CFDs). Ruptured mirror PComAAs were divided into ruptured and unruptured groups. Fourteen morphological and eight hemodynamic parameters were calculated and compared. Significant parameters were analyzed by the multivariate logistic regression to identify independent risk factors. Receiver operating characteristic (ROC) analysis was performed, and the area under the ROC curve (AUC) was calculated for all independent risk factors to determine the predictability and identify the optimal threshold. Results: Four hemodynamic and three morphological parameters were significantly different between ruptured and unruptured groups: normalized wall shear stress (NWSS), mean WSS, low wall shear WSS area (LSA%), size, aspect ratio (AR), size ratio (SR), and inflow angle (IA). Multivariate logistic regression analysis showed that AR, SR, NWSS, mean WSS, and LSA% were all independent factors significantly associated with PComAAs rupture. The ROC analysis for independent risk factors indicated that AR (0.751), NWSS (0.755), mean WSS (0.69), and LSA (0.778) had merely acceptable AUC values. Only SR (0.803) had a high acceptable AUC value. The threshold value of SR was 1.96. Conclusions: SR (>1.96) was the most significant parameter associated with IA rupture, whereas AR, NWSS, mean WSS, and LSA independently characterized the status of IA rupture.

Interleukin-6 in Cerebrospinal Fluid Small Extracellular Vesicles as a Potential Biomarker for Prognosis of Aneurysmal Subarachnoid Haemorrhage.

OBJECTIVE: Aneurysmal subarachnoid hemorrhage (aSAH) is a severe form of stroke characterized by high rates of mortality and disability. Identifying circulating biomarkers is helpful to improve outcomes. In this study, for the first time, we identify interleukin-6 (IL-6) in cerebrospinal fluid (CSF) small extracellular vesicles (sEVs) as potential biomarkers for prognosis of aSAH. METHODS: We extracted small extracellular vesicles from the CSF of 103 aSAH patients and 40 healthy controls in a prospective observational study. Subsequently, we measured IL-6sEVs levels using an enzyme-linked immunosorbent assay. Results were statistically analyzed to determine the function of IL-6sEVs for disease monitoring of aSAH. RESULTS: CSF IL-6 sEVs showed distinct pattern differences between healthy controls and aSAH patients. The concentration of IL-6sEVs in CSF is significantly correlated with the severity of aSAH patients. The areas under the receiver operating characteristic curves of IL-6sEVs for identifying severe aSAH patient from aSAH patients were 0.900. After multivariate logistic regression analysis, IL-6sEVs were associated with neurological outcome at 1 year. IL-6sEVs levels were greater and positively associated with disease processes and outcome. CONCLUSION: There is a neuroinflammatory cascade in aSAH patients. IL-6sEVs in CSF may be a biomarker for the progression of aSAH.

Astaxanthin ameliorates oxidative stress and neuronal apoptosis via SIRT1/NRF2/Prx2/ASK1/p38 after traumatic brain injury in mice.

BACKGROUND AND PURPOSE: Oxidative stress and neuronal apoptosis play key roles in traumatic brain injury. We investigated the protective effects of astaxanthin against traumatic brain injury and its underlying mechanisms of action. EXPERIMENTAL APPROACH: A weight-drop model of traumatic brain injury in vivo and hydrogen peroxide exposure in vitro model were established. Brain oedema, behaviour tests, western blot, biochemical analysis, lesion volume, histopathological study and cell viability were performed. KEY RESULTS: Astaxanthin significantly reduced oxidative insults on Days 1, 3 and 7 after traumatic brain injury. Neuronal apoptosis was also ameliorated on Day 3. Additionally, astaxanthin improved neurological functions up to 3 weeks after traumatic brain injury. Astaxanthin treatment dramatically enhanced the expression of peroxiredoxin 2 (Prx2), nuclear factor-erythroid 2-related factor 2 (NRF2/Nrf2) and sirtuin 1 (SIRT1), while it down-regulated the phosphorylation of apoptosis signal-regulating kinase 1 (ASK1) and p38. Inhibition of Prx2 by siRNA injection reversed the beneficial effects of astaxanthin against traumatic brain injury. Additionally, Nrf2 knockout prevented the neuroprotective effects of astaxanthin in traumatic brain injury. In contrast, overexpression of Prx2 in Nrf2 knockout mice attenuated the secondary brain injury after traumatic brain injury. Moreover, inhibiting SIRT1 by EX527 dramatically inhibited the neuroprotective effects of astaxanthin and suppressed SIRT1/Nrf2/Prx2/ASK1/p38 pathway both in vivo and in vitro. CONCLUSION AND IMPLICATIONS: Astaxanthin improved the neurological functions and protected the brain from injury after traumatic brain injury, primarily by reducing oxidative stress and neuronal death via SIRT1/Nrf2/Prx2/ASK1/p38 signalling pathway and might be a new candidate to ameliorate traumatic brain injury.

Fucoxanthin Mitigates Subarachnoid Hemorrhage-Induced Oxidative Damage via Sirtuin 1-Dependent Pathway.

Oxidative stress is a key component of the pathological cascade in subarachnoid hemorrhage (SAH). Fucoxanthin (Fx) possesses a strong antioxidant property and has shown neuroprotective effects in acute brain injuries such as ischemic stroke and traumatic brain injury. Here, we investigated the beneficial effects of Fx against SAH-induced oxidative insults and the possible molecular mechanisms. Our data showed that Fx could significantly inhibit SAH-induced reactive oxygen species production and lipid peroxidation, and restore the impairment of endogenous antioxidant enzymes activities. In addition, Fx supplementation improved mitochondrial morphology, ameliorated neural apoptosis, and reduced brain edema after SAH. Moreover, Fx administration exerted an improvement in short-term and long-term neurobehavior functions after SAH. Mechanistically, Fx inhibited oxidative damage and brain injury after SAH by deacetylation of forkhead transcription factors of the O class and p53 via sirtuin 1 (Sirt1) activation. EX527, a selective Sirt1 inhibitor, significantly abated Fx-induced Sirt1 activation and abrogated the antioxidant and neuroprotective effects of Fx after SAH. In primary neurons, Fx similarly suppressed oxidative insults and improved cell viability. These effects were associated with Sirt1 activation and were reversed by EX527 treatment. Taken together, our study explored that Fx provided protection against SAH-induced oxidative insults by inducing Sirt1 signaling, indicating that Fx might serve as a potential therapeutic drug for SAH.

Hemodynamic and Morphological Differences Between Unruptured Carotid-Posterior Communicating Artery Bifurcation Aneurysms and Infundibular Dilations of the Posterior Communicating Artery.

Objective: Posterior communicating artery bifurcation aneurysms (PcomA-BAs) and infundibular dilations (PcomA-IDs) are found at the junction between the internal carotid artery (ICA) and the posterior communicating artery (PcomA). Several studies found that PcomA-IDs potentially progress to aneurysms and can even rupture. In our clinical practice, digital subtraction angiography (DSA) helps differentiate PcomA-IDs from unruptured PcomA-BAs. However, when PcomA-IDs are >3 mm in diameter or PcomA are absent on DSA, it is challenging to use DSA to differentiate PcomA-IDs from unruptured PcomA-BAs. Hemodynamic and morphological factors are thought to play important roles in the pathogenesis, progression, and rupture of cerebral aneurysms. We compared hemodynamic and morphological differences in unruptured PcomA-BAs and PcomA-IDs to better manage PcomA-IDs. Methods: We included 83 PcomA-IDs and 115 unruptured PcomA-BAs dignosed and measured using DSA from January 2015 to January 2019. Computational fluid dynamics was performed on these patient-specific models reconstructed using axial slices in DICOM format. Clinical, hemodynamic, and morphological factors were compared between the PcomA-IDs and PcomA-BAs. Significant parameters were analyzed using binary logistic regression analysis to identify independent risk factors. Receiver operating characteristic (ROC) analysis was performed on the independent risk factors to acquire cutoff values. Results: One hemodynamic and four morphyological parameters were significantly different between PcomA-IDs and PcomA-BAs: normalized wall shear stress (NWSS), size, the angle between the ophthalmic segment of the ICA and the PcomA (APcomA), the angle between the ophthalmic and the communicating segment of the ICA (AICA) and the diameter of the PcomA (DPcomA). Binary logistic regression analysis showed that small size and DPcomA as well as APcomA were all independent significant factors characterizing the status of PcomA-IDs and the ROC analysis for independent risk factors indicated the cutoff values of size, APcomA, and DPcomA were 3.45 mm, 66.27°, and 1.24 mm, respectively. Conclusions: Size, DpcomA, and ApcomA could independently characterize the status of PcomA-IDs. These might help us better differentiate them from real aneurysms and guide its management.

Berberine Ameliorates Subarachnoid Hemorrhage Injury via Induction of Sirtuin 1 and Inhibiting HMGB1/Nf-κB Pathway.

Excessive cerebral inflammation plays a key role in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Berberine, an isoquinoline alkaloid isolated from Chinese herb Coptis chinensis, possesses anti-inflammatory, and neuroprotective effects. Here we evaluated the beneficial effects of berberine against SAH-induced inflammatory response and the subsequent brain injury. Our data showed that berberine treatment significantly inhibited microglia activation and proinflammatory cytokines release. Concomitant with suppressed cerebral inflammation, berberine mitigated the subsequent brain injury as demonstrated by improved neurological behavior, reduced brain edema, and decreased neural apoptosis. Moreover, berberine significantly inhibited high mobile group box 1 (HMGB1)/nuclear factor-κB (Nf-κB)-dependent pathway and enhanced sirtuin 1 (SIRT1) expression after SAH. Treatment with ex527, a selective SIRT1 inhibitor, reversed berberine-induced SIRT1 activation and inhibitory effects on HMGB1/Nf-κB activation. In addition, ex527 pretreatment abated the anti-inflammatory and neuroprotective effects of berberine on SAH. Taken together, these findings suggest that berberine provides beneficial effects against SAH-triggered cerebral inflammation by inhibiting HMGB1/Nf-κB pathway, which may be modulated by SIRT1 activation.

Hemodynamic and Morphological Analysis of Mirror Aneurysms Prior to Rupture.

OBJECTIVE: Hemodynamic factors are thought to play important roles in the pathogenesis, progression, and rupture of cerebral aneurysms. Previous hemodynamic studies have been based on comparisons between post-ruptured and unruptured aneurysms. Nevertheless, changes of aneurysm morphology after rupture render these results unreliable. Moreover, pressure, age, gender, and the morphology of the parent artery also influence these results. Therefore, in the present study, we identified hemodynamic and morphological characteristics of aneurysms prior to rupture using twelve mirror aneurysms. MATERIALS AND METHODS: From our database, we retrospectively analyzed twelve mirror aneurysms (MANs) prior to rupture. Each mirror aneurysm was divided into the prior to rupture or the unruptured group. Patient-specific models were reconstructed from three-dimensional (3D) images of all patients. Hemodynamic and morphological factors were analyzed and compared. RESULTS: Compared with the unruptured side of MANs, aneurysms prior to rupture were significantly larger and significantly more irregular in shape; they also had significantly higher aspect ratio (AR), size ratio (SR), undulation index (UI), ellipticity index (EI), percentage of low wall shear stress area (LSA) and significantly lower normal wall shear stress (NWSS). The oscillatory shear index (OSI) and nonsphericity index (NSI) in the aneurysms prior to rupture were non-significantly higher than those of the unruptured group. CONCLUSION: MANs prior to rupture may be extremely useful models to assess the risk of aneurysm rupture. Larger size, irregular shape, higher AR, SR, UI, NI, and lower WSS may be associated with aneurysms at risk for rupture.

Effect of peer presence on adolescents' risk-taking is moderated by individual self-esteem: An experimental study.

Prior research suggests that the presence of peers increases adolescents' risk-taking. However, it is not clear whether the effect of peer presence is moderated by individual characteristics such as self-esteem, since individuals with low self-esteem are more susceptible to peer influence theoretically. The present study examined this problem using an adapted Stoplight Game in an experiment. A final sample of 140 adolescent students aged 14-18 (M = 16.25 ± 0.73 years, 61 girls), divided into two groups-low self-esteem and high self-esteem, according to their self-esteem scores, completed a risk-taking task either alone or in the presence of a same-sex peer. The results indicated that peer presence increased adolescents' risk-taking, specifically for those with low self-esteem, while those with high self-esteem were not affected by peer presence. The findings are helpful for our understanding of peer influence on adolescent risk-taking and the moderating role of the self and have practical implications for preventing and intervening adolescents' risk-taking via increasing their self-esteem.

External ventricular drainage combined with continuous lumbar drainage in the treatment of ventricular hemorrhage.

Objective: Intraventricular hemorrhage (IVH) is characterized by acute onset, rapid progression, and high disability and mortality rates. In this study, we investigated the clinical effect of external ventricular drainage combined with continuous lumbar drainage in IVH treatments. Methods: 114 patients with IVH treated at the Department of Neurosurgery, First Affiliated Hospital of Wannan Medical College from January 2015 to December 2017, were included in the study. Based on the different surgical methods, patients were divided into control (n=79) and study groups (n=35). The control group was treated with external ventricular drainage, whereas the study group was treated with external ventricular drainage combined with continuous lumbar drainage. The incidence of intracranial infection and hydrocephalus was compared between the two groups. The Glasgow coma scale (GCS) and the Glasgow outcome scale (GOS) were compared between the two groups 7 days postoperatively and at follow-up visits, respectively. Results: The incidence of intracranial infection and hydrocephalus in the study group was significantly lower compared with those in the control group (P<0.05). Seven days postoperatively, the GCS score of the study group was significantly higher than that of the control group (P<0.05). At the 3-month follow-up visit, the GOS score of the study group was higher than that of the control group (P<0.05). Conclusions: Using external ventricular drainage combined with continuous lumbar drainage can reduce the incidence of intracranial infection and hydrocephalus and improve the prognoses and quality of life in patients with IVH.

Alpha lipoic acid inhibits oxidative stress-induced apoptosis by modulating of Nrf2 signalling pathway after traumatic brain injury.

Alpha lipoic acid (ALA) is a powerful antioxidant which has been widely used in the treatment of different system diseases, such as cardiovascular and cerebrovascular diseases. But, there are few studies that refer to protective effects and potential mechanisms on traumatic brain injury (TBI). This study was carried out to investigate the neuroprotective effect following TBI and illuminate the underlying mechanism. Weight drop-injured model in rats was induced by weight-drop. ALA was administrated via intraperitoneal injection after TBI. Neurologic scores were examined following several tests. Neurological score was performed to measure behavioural outcomes. Nissl staining and TUNEL were performed to evaluate the neuronal apoptosis. Western blotting was engaged to analyse the protein content of the Nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream protein factors, including hemeoxygenase-1 (HO-1) and quinine oxidoreductase-1 (NQO1). ALA treatment alleviated TBI-induced neuron cell apoptosis and improved neurobehavioural function by up-regulation of Nrf2 expression and its downstream protein factors after TBI. This study presents new perspective of the mechanisms responsible for the neuronal apoptosis of ALA, with possible involvement of Nrf2 pathway.

Persistent High Levels of miR-502-5p Are Associated with Poor Neurologic Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: To investigate the temporal changes in miR-502-5p expression after aneurysmal subarachnoid hemorrhage (aSAH) and to find the time to peak level. METHODS: We collected serum from patients with aSAH (n = 129) at various time points (1, 3, 7, and 14 days postevent) and healthy controls (n = 40) at the Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College, from May 1, 2015 to January 31, 2016. We measured expression levels of miR-502-5p by polymerase chain reaction. We used the 2-ΔCt method and calculated correlations among variables using Spearman rank correlation coefficient analysis. We used receiver operating characteristic curves to identify optimal levels of miR-502-5p for aSAH and multivariate logistic regression to analyze risk factors on the modified Rankin scale. We measured miR-502-5p expression at all 4 time points post-aSAH. RESULTS: Levels rose moderately from day 1 to day 7, with a substantial decrease from day 7 to day 14. The peak was at day 7. Multivariate logistic regression revealed that higher miR-502-5p levels at 7 days were associated with a significantly high risk for poor outcome post-aSAH. CONCLUSIONS: Our data suggest that persistent elevated levels of miR-502-5p participate in the development of aSAH and may help physicians to adjust therapy for aSAH.

Inhibition of leukotriene B4 synthesis protects against early brain injury possibly via reducing the neutrophil-generated inflammatory response and oxidative stress after subarachnoid hemorrhage in rats.

Leukotriene B4 (LTB4) is a highly potent neutrophil chemoattractant and neutrophils induces inflammatory response and oxidative stress when they recruit to and infiltrate in the injuried/inflamed site, such as the brain parenchyma after aneurysmal subarachnoid hemorrhage (SAH). This study is to investigate the potential effects of inhibition of LTB4 synthesis on neutrophil recruitment, inflammatory response and oxidative stress, as well as early brain injury (EBI) in rats after SAH. A pre-chiasmatic cistern SAH model of rats was used in this experiment. SC 57461A was used to inhibit LTB4 synthesis via intracerebroventricular injection. The brain tissues of temporal lobe after SAH were analyzed. Neuronal injury, brain edema and neurological function were evaluated to investigate the development of EBI. We found that inhibition of LTB4 synthesis after SAH could reduce the level of myeloperoxidase, alleviate the inflammatory response and oxidative stress, and reduce neuronal death in the brain parenchyma, and ameliorate brain edema and neurological behavior impairment at 24h after SAH. These results suggest that inhibition of LTB4 synthesis might alleviate EBI after SAH possibly via reducing the neutrophil-generated inflammatory response and oxidative stress.

Pentoxifylline Alleviates Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats: Possibly via Inhibiting TLR 4/NF-κB Signaling Pathway.

Early brain injury (EBI) after subarachnoid hemorrhage (SAH) generally causes significant and lasting damage. Pentoxifylline (PTX), a nonselective phosphodiesterase inhibitor, has shown anti-inflammatory and neuroprotective properties in several brain injury models, but the role of PTX with respect to EBI following SAH remains uncertain. The purpose of this study was to investigate the effects of PTX on EBI after SAH in rats. Adult male Sprauge-Dawley rats were randomly assigned to the sham and SAH groups. PTX (30 or 60 mg/kg) or an equal volume of the administration vehicle (normal saline) was administrated at 30 min intervals following SAH. Neurological scores, brain edema, and neural cell apoptosis were evaluated. In order to explore other mechanisms, changes in the toll-like receptor 4 (TLR4) and the nuclear factor-κB (NF-κB) signaling pathway, in terms of the levels of apoptosis-associated proteins, were also investigated. We found that administration of PTX (60 mg/kg) notably improved neurological function and decreased brain edema at both 24 and 72 h following SAH. Treatment with PTX (60 mg/kg) significantly inhibited the protein expressions of TLR4, NF-κB, MyD88 and the downstream pro-inflammatory cytokines, such as the tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß). PTX also significantly reduced neural cell death and BBB permeability. Our observations may be the first time that PTX has been shown to play a neuroprotective role in EBI after SAH, potentially by suppressing the TLR4/NF-κB inflammation-related pathway in the rat brain.

Cerebral Syphilitic Gumma Misdiagnosed as a Malignant Brain Tumor.

Syphilitic gumma involvement of the central nervous system is extremely rare and frequently misdiagnosed. The authors report a patient of a cerebral syphilitic gumma resembling a malignant brain tumor in a 62-year-old male. He was first suspected of a malignant brain tumor, but the pathological diagnosis was cerebral syphilitic gumma. This patient with unusual findings illustrates the clinical manifestations, imaging, and therapeutic aspects of cerebral syphilitic gumma.