Propofol Reduces Inflammatory Brain Injury after Subarachnoid Hemorrhage: Involvement of PI3K/Akt Pathway

Background: Our previous study showed that propofol, one of the widely used anesthetic agents, can attenuate subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) via inhibiting inflammatory and oxidative reaction. However, it is perplexing whether propofol attenuates inflammatory and oxidative reaction through modulating PI3K/Akt pathway. The present study investigated whether PI3K/Akt pathway is involved in propofol's anti-inflammation, antioxidation, and neuroprotection against SAH-induced EBI. Materials and methods: Adult Sprague-Dawley rats underwent SAH and received treatment with propofol or vehicle after 2 and 12 hours of SAH. LY294002 was injected intracerebroventricularly to selectively inhibit PI3K/Akt signaling. Mortality, SAH grading, neurological scores, brain water content, evans blue extravasation, myeloperoxidase, malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured 24 hours after SAH. Immunoreactivity of p-Akt, t-Akt, nuclear factor- kappa B (NF-κB) p65, nuclear factor erythroid-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase (NQO1), and cyclooxygenase-2 (COX-2) in rat brain was determined by western blot. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in rat brain were examined by ELISA. Results: Propofol significantly reduces neurological dysfunction, BBB permeability, brain edema, inflammation, and oxidative stress, all of which were reversed by LY294002. Propofol significantly upregulates the immunoreactivity of p-Akt, Nrf2, and NQO1, all of which were abolished by LY294002. Propofol significantly downregulates the overexpression of NF-κB p65, COX-2, TNF-α, and IL-1β, all of which were inhibited by LY294002. Conclusion: These results suggest that propofol attenuates SAH-induced EBI by inhibiting inflammatory reaction and oxidative stress, which might be associated with the activation of PI3K/Akt signaling pathway.     

TSG-6 Attenuates Oxidative Stress-Induced Early Brain Injury in Subarachnoid Hemorrhage Partly by the HO-1 and Nox2 Pathways

BackgroundEarly brain injury (EBI) refers to acute brain injury during the first 72 h after subarachnoid hemorrhage (SAH), which is one of the major causes of poor prognosis after SAH. Here, we investigated the effect and the related mechanism of TSG-6 on EBI after SAH.Materials and methodsThe Sprague-Dawley rat model of SAH was developed by the endovascular perforation method. TSG-6 (5μg) was administered by an intraventricular injection within 1.5 h after SAH. The effects of TSG-6 on EBI were assessed by neurological score, brain water content (BWC) and TUNEL staining. Immunofluorescence staining was used to assay NF-κB/p-NF-κB expression in microglia. Protein expression levels of heme oxygenase-1 (HO-1), NADPH oxidase 2 (Nox2), Bcl-2, Bax, and cleaved-caspase-3 were measured to investigate the potential mechanism. The enzyme activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the level of reactive oxygen species (ROS) were analyzed using commercially available kits.ResultsThe results showed that TSG-6 treatment alleviated the neurobehavioral dysfunction and reduced BWC and the number of TUNEL-positive neurons in EBI after SAH. TSG-6 decreased the ROS level and enhanced the enzyme activity of SOD and GSH-Px after SAH. Furthermore TSG-6 inhibited the NF-κB activation, increased the protein expression levels of HO-1 and Bcl-2 and decreased the expression levels of Nox2, Bax, and cleaved-caspase-3. The administration of TSG-6 siRNA abolished the protective effects of TSG-6 on EBI after SAH.ConclusionWe found that TSG-6 attenuated oxidative stress and apoptosis in EBI after SAH partly by inhibiting NF-κB and activating HO-1 pathway in brain tissue.     

Role of autophagy in early brain injury after experimental subarachnoid hemorrhage

Autophagy is a self-degradative process and it plays a housekeeping role in removing misfolded or aggregated proteins, clearing damaged organelles, and eliminating intracellular pathogens. Previous studies have demonstrated that autophagy pathway was activated in brain after experimental subarachnoid hemorrhage (SAH); however, the role of autophagy in the pathogenesis of early brain injury (EBI) following SAH remains unknown. Experiment 1 aimed to investigate the time–course of the autophagy in the cortex following SAH. In experiment 2, we chose the maximum time pointof autophagy activation and assessed the effects of rapamycin (RAP, autophagy activator) and 3-methyladenine (3-MA, autophagy inhibitor) on regulation of EBI. All SAH animals were subjected to injection of 0.3 ml fresh arterial, nonheparinized blood into prechiasmatic cistern in 20 s. As a result, microtubule-associated protein light chain-3 (LC3), a biomarker of autophagosome, and beclin-1, a Bcl-2-interacting protein required for autophagy, were significantly increased at the early stage of SAH and their expressions peaked at 24 h after SAH. In RAP-treated group, the early brain damage such as brain edema, blood–brain barrier (BBB) impairment, cortical apoptosis, and clinical behavior scale was significantly ameliorated in comparison with vehicle-treated SAH rats. Conversely, 3-MA decreased expression of LC3 and beclin-1, increased the average value of brain edema and BBB disfunction, and aggravated neurological deficits. Our results suggest that autophagy pathway is activated in the brain after SAH and may play a beneficial role to EBI development.     

葛根素通过Nrf2-ARE信号通路抵抗氧化应激对创伤性脑损伤的神经保护作用

目的 探讨葛根素对创伤性脑损伤(TBI)模型大鼠的神经保护作用及脑组织红系衍生的核因子相关因子2(Nrf2)一抗氧化反应原件(ARE)信号通路参与的机制。方法 选择健康成年雄性大鼠体重250～300 g构建TBI模型,将大鼠分为4组:创伤组(A组)、假手术组(B组)、葛根素治疗的创伤组(C组)和葛根素治疗的假手术组(D组); 通过采用改良的神经功能缺损评分(mNSS)评价神经功能,脑组织干湿重称量法评价脑水肿,Nissl染色,TUNEL染色评价脑损伤体积和神经元的凋亡,使用酶活试剂盒检测损伤48 h后抗氧化酶SOD,GSH,和GSSG的活性以及氧化应激产物MDA和NO的水平,最后使用western blot和RT-PCR的方法检测Nrf2-ARE信号通路及其下游分子HO-1,NQO1的表达水平。结果 TBI手术后损伤组mNSS评分明显增高(P<0.05),葛根素治疗组能够明显降低mNSS评分(P<0.05)。TBI手术后损伤组脑水肿加重及神经元凋亡增加(P<0.05),葛根素治疗组能够明显挽救脑水肿及神经元凋亡(P<0.05)。TBI手术12 h后损伤组脑内抗氧化酶SOD,GSH,和GSSG的活性增加及氧化应激产物MDA和NO的水平升高(P<0.05),葛根素治疗组能够明显降低抗氧化酶SOD,GSH,和GSSG的活性以及氧化应激产物MDA和NO的水平(P<0.05)。western blot和RT-PCR显示葛根素不改变Nrf2的翻译和表达,但是RT-PCR显示葛根素能够明显促进Nrf2-ARE信号通路下游分子HO-1,NQO1的表达。结论 葛根素可能通过Nrf2-ARE信号通路抵抗氧化应激对创伤性脑损伤发挥神经保护作用。     

大鼠蛛网膜下腔出血后脑皮层中LC3和Beclin-1表达的变化

目的 探讨蛛网膜下腔出血(SAH)后SD 大鼠脑皮层中自噬标志物LC3 和Beclin-1 表达的变化.方法 雄性SD 大鼠30 只,随机分为对照组和SAH 组,采用视交叉池注血技术造成蛛网膜下腔出血模型,SAH 组分别于蛛网膜下腔出血后6 h、12 h、24 h、48 h 后取额底和颞底脑皮层,分别用western blot 技术和免疫组化技术测定自噬标志物LC3 和Beclin-1 的变化.结果 与对照组相比,蛛网膜下腔出血后自噬标志物LC3 于6 h(P＜0.05)后明显升高,24 h(P＜0.01)达到高峰,之后开始下降,同样Beclin-1 也于6 h(P＜0.05)后明显升高,24 h(P＜0.01)达到高峰,之后开始下降.结论 蛛网膜下腔出血后脑皮层中自噬途径被激活,并在24 h 时活性最强,因此自噬在蛛网膜下腔出血后的急性期脑损伤中可能起重要作用.     

Nuclear factor erythroid 2-related factor 2 protects against beta amyloid

Nuclear factor erythroid 2-related factor 2 (Nrf2) coordinates the up-regulation of cytoprotective genes via the antioxidant response element (ARE). In the pathogenesis of Alzheimer's disease (AD) current evidence supports the role of oxidative stress. Considering the protective role of Nrf2 against oxidative injury, we studied Nrf2 and Nrf2-ARE target genes in transgenic AD mice and tested whether Nrf2 could confer neuroprotection against amyloid-beta peptides (Abeta). Nrf2-ARE pathway was attenuated in APP/PS1 transgenic mouse brain at the time of Abeta deposition. Boosting the activity of the Nrf2-ARE pathway by tert-butylhydroquinone treatment or adenoviral Nrf2 gene transfer protected against Abeta toxicity. This neuroprotection was associated with increased expression of Nrf2 target genes and reduced phosphorylation of p66Shc, a marker of increased susceptibility for oxidative stress. The findings suggest that the Nrf2-ARE pathway may be impaired in AD and that induction of the Nrf2-ARE defence mechanism may prevent or delay AD-like pathology.     

Activation of the Nrf2-ARE signal pathway after blast induced traumatic brain injury in mice

Background: Treatment of blast-induced traumatic brain injury (bTBI) has been hindered. Previous studies have demonstrated that oxidative stress may contribute to the pathophysiological process. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) signaling pathway exhibits a protective effect after traumatic brain injury (TBI). This study explored whether the Nrf2-ARE pathway was activated in a modified bTBI mouse model.

Method: Mice were randomly divided into six groups: the 6?h, 1 d, 3 d, 7 d and 14 d after bTBI groups and a sham group. The protein levels of nuclear Nrf2, heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO1) were detected using western blot, and HO-1 and NQO1 mRNA levels were determined by real-time quantitative polymerase chain reaction. Moreover, HO-1 and Nrf2 were localized using histological staining.

Results: The protein level of the Nrf2-ARE pathway in the frontal lobe increased significantly in the 3 d after bTBI. The HO-1 and NQO1 mRNA levels also reached a peak in the frontal lobe 3 d after bTBI. The histological staining demonstrated higher expression of HO-1 in the frontal lobe and hippocampus 3 d after bTBI, when nuclear import of Nrf2 reached a peak in the frontal lobe.

Conclusions: bTBI activated the Nrf2-ARE signaling pathway in the brain. The peak activation time in the frontal lobe may be 3 d after injury, and activating the Nrf2 pathway could be a new direction for treatment.     

Nuclear receptor nur77 promotes cerebral cell apoptosis and induces early brain injury after experimental subarachnoid hemorrhage in rats

Nur77 is a potent proapoptotic member of the nuclear receptor superfamily that is expressed predominantly in brain tissue. It has been demonstrated that Nur77 mediates apoptosis in multiple organs. Nur77‐mediated early brain injury (EBI) involves a conformational change in BCL‐2 and triggers cytochrome C (cytoC) release resulting in cellular apoptosis. This study investigates whether Nur77 can promote cerebral cell apoptosis after experimentally induced subarachnoid hemorrhage (SAH) in rats. Sprague Dawley rats were randomly assigned to three groups: 1) untreated group, 2) treatment control group, and 3) SAH group. The experimental SAH group was divided into four subgroups, corresponding to 12 hr, 24 hr, 48 hr, and 72 hr after experimentally induced SAH. It remains unclear whether Nur77 can play an important role during EBI after SAH as a proapoptotic protein in cerebral cells. Cytosporone B (Csn‐B) was used to demonstrate that Nur77 could be enriched and used to aggravate EBI after SAH. Rats treated with Csn‐B were given an intraperitoneal injection (13 mg/kg) 30 min after experimentally induced SAH. We found that Nur77 promotes cerebral cell apoptosis by mediating EBI and triggering a conformational change in BCL‐2, resulting in cytoC release. Nur77 activity, along with cerebral cell apoptosis, peaked at 24 hr after SAH onset. After induction of SAH, an injection of Csn‐B, an agonist for Nur77, enhanced the expression and function of Nur77. In summary, we have demonstrated the proapoptotic effect of Nur77 within cerebral cells, an effect that can be further exacerbated with Csn‐B stimulation. © 2014 Wiley Periodicals, Inc.     

Acyl-CoA synthetase long chain family member 4 plays detrimental role in early brain injury after subarachnoid hemorrhage in rats by inducing ferroptosis

AimsAcyl‐CoA synthetase long chain family member 4 (ACSL4) is closely related to tumor genesis and development in certain tissues. However, the function of ACSL4 in early brain injury (EBI) caused by subarachnoid hemorrhage (SAH) is unclear. In this study, we investigated the expression patterns and role of ACSL4 in SAH and post‐SAH EBI using a rat model of SAH.MethodsThe rat model of SAH was induced by autologous blood injection into the prechiasmatic cistern of rats. We also used two specific inhibitors of ferroptosis (Ferrostatin‐1 and Liproxstatin‐1) to investigate the role of ferroptosis in EBI.ResultsWe found that ACSL4 levels in brain tissue increased significantly in post‐SAH EBI. Inhibiting the expression of ACSL4 using small interfering RNAs alleviated inflammation, blood‐brain barrier (BBB) impairment, oxidative stress, brain edema, and behavioral and cognitive deficits, and increased the number of surviving neurons, after SAH. Similar effects were obtained by suppressing ferroptosis.ConclusionsACSL4 exacerbated SAH‐induced EBI by mediating ferroptosis. These findings may provide a theoretical basis for potential therapy aimed at alleviating post‐SAH EBI.     

Fluoxetine is Neuroprotective in Early Brain Injury <Emphasis Type="Italic">via</Emphasis> its Anti-inflammatory and Anti-apoptotic Effects in a Rat Experimental Subarachnoid Hemorrhage Model

Fluoxetine, an anti-depressant drug, has recently been shown to provide neuroprotection in central nervous system injury, but its roles in subarachnoid hemorrhage (SAH) remain unclear. In this study, we aimed to evaluate whether fluoxetine attenuates early brain injury (EBI) after SAH. We demonstrated that intraperitoneal injection of fluoxetine (10 mg/kg per day) significantly attenuated brain edema and blood-brain barrier (BBB) disruption, microglial activation, and neuronal apoptosis in EBI after experimental SAH, as evidenced by the reduction of brain water content and Evans blue dye extravasation, prevention of disruption of the tight junction proteins zonula occludens-1, claudin-5, and occludin, a decrease of cells staining positive for Iba-1, ED-1, and TUNEL and a decline in IL-1β, IL-6, TNF-α, MDA, 3-nitrotyrosine, and 8-OHDG levels. Moreover, fluoxetine significantly improved the neurological deficits of EBI and long-term sensorimotor behavioral deficits following SAH in a rat model. These results indicated that fluoxetine has a neuroprotective effect after experimental SAH.     

4＇，5，7-三羟基异黄酮对蛛网膜下腔出血大鼠的神经保护和抗氧化作用研究

目的探讨4＇,5,7-三羟基异黄酮对蛛网膜下腔出血（SAH）后的神经保护作用。方法对大鼠单次枕大池注血模型分别以10mg／kg、50mg／kg浓度腹腔注射4＇,5,7-三羟基异黄酮,观察大鼠脑水肿、血脑屏障（BBB）的通透性、氧化应激和血红素氧合酶-1（HO-1）的变化情况。结果4＇,5,7-羟基异黄酮可以减轻SAH后脑水肿,降低BBB通透性、缓解氧化应激状态及减少HO-1的表达。结论4＇,5,7-三羟基异黄酮可能是通过提高内源性抗氧化酶的表达和抑制自由基的产生,从而在SAH中产生神经功能保护作用。     

舒芬太尼对大鼠蛛网膜下腔出血后脑损伤的保护作用

目的 探讨舒芬太尼对大鼠蛛网膜下腔出血(SAH)后脑损伤的作用及其机制.方法 取60只成年SD大鼠随机分为假手术组、模型组和舒芬太尼组,每组20只.采用血管内穿孔法建立SAH模型,舒芬太尼组建模后6h尾静脉注射舒芬太尼溶液(5 μg/kg,1次/d,连续3周),假手术组和模型组尾静脉注射等量生理盐水.造模后1、2、21...     

Nuclear factor‐κB/Bcl‐XL pathway is involved in the protective effect of hydrogen‐rich saline on the brain following experimental subarachnoid hemorrhage in rabbits

Early brain injury (EBI), a significant contributor to poor outcome after subarachnoid hemorrhage (SAH), is intimately associated with neuronal apoptosis. Recently, the protective role of hydrogen (H₂) in the brain has been widely studied, but the underlying mechanism remains elusive. Numerous studies have shown nuclear factor‐κB (NF‐κB) as a crucial survival pathway in neurons. Here we investigated the role of H₂ in EBI following SAH, focusing on the NF‐κB pathway. A double blood injection model was used to produce experimental SAH, and H₂‐rich saline was injected intraperitoneally. NF‐κB activity within the occipital cortex was measured. Immunofluorescence was performed to demonstrate the activation of NF‐κB; Bcl‐xL and cleaved caspase‐3 were determined via Western blot. Gene expression of Bcl‐xL was detected by real‐time PCR, and TUNEL and Nissl staining were performed to illustrate brain injury in the occipital cortex. SAH induced a significant increase of cleaved caspase‐3. Correspondingly, TUNEL staining demonstrated obvious neuronal apoptosis following SAH. In contrast, H₂ treatment markedly increased NF‐κB activity and the expression of Bcl‐xL and decreased the level of cleaved caspase‐3. Additionally, H₂ treatment significantly reduced post‐SAH neuronal apoptosis. The current study shows that H₂ treatment alleviates EBI in the rabbits following SAH and that NF‐κB/Bcl‐xL pathway is involved in the protective role of H₂. © 2013 Wiley Periodicals, Inc.     

INT-777 attenuates NLRP3-ASC inflammasome-mediated neuroinflammation via TGR5/cAMP/PKA signaling pathway after subarachnoid hemorrhage in rats

BackgroundInflammasome-mediated neuroinflammation plays an important role in the pathogenesis of early brain injury (EBI) following subarachnoid hemorrhage (SAH). The activation of the TGR5 receptor has been shown to be neuroprotective in a variety of neurological diseases. This study aimed to investigate the effects of the specific synthetic TGR5 agonist, INT-777, in attenuating NLRP3-ASC inflammasome activation and reducing neuroinflammation after SAH.MethodsOne hundred and eighty-four male Sprague Dawley rats were used. SAH was induced by the endovascular perforation. INT-777 was administered intranasally at 1 h after SAH induction. To elucidate the signaling pathway involved in the effect of INT-777 on inflammasome activation during EBI, TGR5 knockout CRISPR and PKA inhibitor H89 were administered intracerebroventricularly and intraperitoneally at 48 h and 1 h before SAH. The SAH grade, short- and long-term neurobehavioral assessments, brain water content, western blot, immunofluorescence staining, and Nissl staining were performed.ResultsThe expressions of endogenous TGR5, p-PKA, and NLRP3-ASC inflammasome were increased after SAH. INT-777 administration significantly decreased NLRP3-ASC inflammasome activation in microglia, reduced brain edema and neuroinflammation, leading to improved short-term neurobehavioral functions at 24 h after SAH. The administration of TGR5 CRISPR or PKA inhibitor (H89) abolished the anti-inflammation effects of INT-777, on NLRP3-ASC inflammasome, pro-inflammatory cytokines (IL-6, IL-1β, and TNF-a), and neutrophil infiltration at 24 h after SAH. Moreover, early administration of INT-777 attenuated neuronal degeneration in hippocampus on 28 d after SAH.ConclusionsINT-777 attenuated NLRP3-ASC inflammasome-dependent neuroinflammation in the EBI after SAH, partially via TGR5/cAMP/PKA signaling pathway. Early administration of INT-777 may serve as a potential therapeutic strategy for EBI management in the setting of SAH.     

Apigenin attenuates oxidative stress and neuronal apoptosis in early brain injury following subarachnoid hemorrhage

Apigenin (API) is a naturally occurring plant flavone that exhibits powerful antioxidant and antiapoptosis. Oxidative stress plays an important role in the pathogenesis of early brain injury (EBI) following subarachnoid hemorrhage (SAH). The potential anti-oxidative and anti-apoptosis effects of API on EBI following SAH, however, have not been elucidated. The aim of this study was to assess whether API alleviates EBI after SAH via its anti-oxidative and anti-apoptotic effects. The endovascular puncture model was used to induce SAH and all the rats were subsequently sacrificed at 24 h after SAH. Our data demonstrated that administration of API could significantly alleviate EBI (including neurological deficiency, brain edema, blood–brain barrier permeability, and cortical cell apoptosis) after SAH in rats. Meanwhile, API treatment reduced the reactive oxygen species (ROS) level and the concentration of malondialdehyde (MDA) and myeloperoxidase (MPO), elevated the ratio of glutathione (GSH) and oxidized glutathione (GSSG), and increased the amount of super-oxide dismutase (SOD) and hydrogen peroxide in brain cortex at 24 h following SAH. Moreover, API treatment inhibited SAH-induced the expression of Bax and caspase-3, significantly reduced neuronal apoptosis. Collectively, API exerts its neuroprotective effect likely through the dual activities of anti-oxidation and anti-apoptosis, at least partly. These data provide a basic platform to consider API may be safely used as a potential drug for treatment of SAH.     

Fluoxetine is Neuroprotective in Early Brain Injury via its Antiinflammatory and Anti-apoptotic Effects in a Rat Experimental Subarachnoid Hemorrhage Model

Fluoxetine, an anti-depressant drug, has recently been shown to provide neuroprotection in central nervous system injury, but its roles in subarachnoid hemorrhage(SAH) remain unclear. In this study, we aimed to evaluate whether fluoxetine attenuates early brain injury(EBI) after SAH. We demonstrated that intraperitoneal injection of fluoxetine(10 mg/kg per day) significantly attenuated brain edema and blood-brain barrier(BBB) disruption, microglial activation, and neuronal apoptosis in EBI after experimental SAH, as evidenced by the reduction of brain water content and Evans blue dye extravasation, prevention of disruption of the tight junction proteins zonula occludens-1, claudin-5, and occludin, a decrease of cells staining positive for Iba-1, ED-1, and TUNEL and a decline in IL-1 b, IL-6, TNF-a, MDA, 3-nitrotyrosine, and 8-OHDG levels. Moreover, fluoxetine significantly improved the neurological deficits of EBI and long-term sensorimotor behavioral deficits following SAH in a rat model. These results indicated that fluoxetine has a neuroprotective effect after experimental SAH.     

Heme-oxygenase-1 induction in glia throughout rat brain following experimental subarachnoid hemorrhage

The heme released following subarachnoid hemorrhage is metabolized by heme-oxygenase (HO) to biliverdin and carbon monoxide (CO) with the release of iron. The HO reaction is important since heme may contribute to vasospasm and increase oxidative stress in cells. HO is comprised of at least two isozymes, HO-2 and HO-1. HO-1, also known as heat shock protein HSP32, is inducible by many factors including heme and heat shock. HO-2 does not respond to these stresses. To begin to examine HO activity following subarachnoid hemorrhage (SAH), the expression of HO-1 and HO-2 was investigated after experimental SAH in adult rats. Immunocytochemistry for HO-1, HO-2 and HSP70 proteins was performed at 1, 2, 3 and 4 days after injections of lysed blood, whole blood, oxyhemoglobin and saline into the cisterna magna. A large increase in HO-1 immunoreactivity was seen in cells throughout brain following injections of lysed blood, whole blood, and oxyhemoglobin but not saline. Lysed blood, whole blood and oxyhemoglobin induced HO-1 in all of the cortex, hippocampus, striatum, thalamus, forebrain white matter and in cerebellar cortex. HO-1 immunoreactivity was greatest in those regions adjacent to the basal subarachnoid cisterns where blood and oxyhemoglobin concentrations were likely highest. Double immunofluorescence studies showed the HO-1 positive cells to be predominately microglia, though HO-1 was induced in some astrocytes. HO-1 expression resolved by 48 h. HO-2 immunoreactivity was abundant but did not change following injections of blood. A generalized induction of HSP70 heat shock protein was not observed following injections of lysed blood, whole blood, oxyhemoglobin, or saline. These results suggest that HO-1 is induced in microglia throughout rat brain as a general, parenchymal response to the presence of oxyhemoglobin in the subarachnoid space and not as a stress response. This microglial HO-1 response could be protective against the lipid peroxidation and vasospasm induced by hemoglobin, by increasing heme clearance and iron sequestration, and enhancing the production of the antioxidant bilirubin.     

黄体酮对蛛网膜下腔出血后皮层TLR4/NF-κB传导通路的影响

目的 探讨黄体酮对蛛网膜下腔出血(SAH)所致的早期脑损伤(EBI)后大脑皮层Toll 样受体4(TLR4)/核因子-κB(NF-κB)传导通路的调控作用.方法 雄性SD 大鼠32 只,随机分为对照组、蛛血组、安慰剂组及黄体酮组,取大鼠尾动脉非肝素化动脉血注入视交叉前池致蛛网膜下腔出血模型,黄体酮注射剂量为16 mg/...     

蛛网膜下腔出血后早期脑损伤的研究进展

蛛网膜下腔出血(SAH)是由多种脑血管疾病引起的一种复杂的临床综合征,可对中枢神经系统产生灾难性打击,其高致残率、病死率显著影响了患者的神经认知功能恢复,加重家庭和社会经济负担。其中颅内动脉瘤破裂出血是SAH最常见的病因(85%)。近年来,多项研究表明早期脑损伤(EBI)是导致蛛网膜下腔出血预后不良的重要因素。脑表面或脑底部血管破裂后,血液进入蛛网膜下腔的血液引起机体强烈的神经炎症反应,表现为小胶质细胞活化,外周免疫细胞募集,微循环障碍,血脑屏障破坏和神经细胞凋亡。本研究总结了目前已知的有关EBI的病理生理机制,同时讨论了蛛网膜下腔出血后EBI的潜在治疗靶点。