Steering lithium and potassium storage mechanism in covalent organic frameworks by incorporating transition metal single atoms.

Organic electrodes mainly consisting of C, O, H, and N are promising candidates for advanced batteries. However, the sluggish ionic and electronic conductivity limit the full play of their high theoretical capacities. Here, we integrate the idea of metal-support interaction in single-atom catalysts with π-d hybridization into the design of organic electrode materials for the applications of lithium (LIBs) and potassium-ion batteries (PIBs). Several types of transition metal single atoms (e.g., Co, Ni, Fe) with π-d hybridization are incorporated into the semiconducting covalent organic framework (COF) composite. Single atoms favorably modify the energy band structure and improve the electronic conductivity of COF. More importantly, the electronic interaction between single atoms and COF adjusts the binding affinity and modifies ion traffic between Li/K ions and the active organic units of COFs as evidenced by extensive in situ and ex situ characterizations and theoretical calculations. The corresponding LIB achieves a high reversible capacity of 1,023.0 mA h g-1 after 100 cycles at 100 mA g-1 and 501.1 mA h g-1 after 500 cycles at 1,000 mA g-1. The corresponding PIB delivers a high reversible capacity of 449.0 mA h g-1 at 100 mA g-1 after 150 cycles and stably cycled over 500 cycles at 1,000 mA g-1. This work provides a promising route to engineering organic electrodes.

Rhein induces apoptosis and autophagy in human and rat glioma cells and mediates cell differentiation by ERK inhibition.

In this study, we investigated the anticancer potentials of Rhein, an anthraquinone derivative of most commonly used Chinese rhubarb on the rat F98 glioma cells. The experimental studies revealed that Rhein induced cell cycle arrest, caspase mediated apoptosis. It results in the formation of intracellular acidic vesicles in cytoplasm, leading to autophagy. Differentiation of viable cells towards elongation of matured astrocytes was proved by monitoring dramatic changes in morphological characteristics as well as identified from the elevation of glial fibrillary acidic protein (GFAP) expression. Rhein treatment did not alter the phosphorylated MAPKs activation including p-38, JNK and NF-κB, transcription unit whereas rhein significantly inhibited ERK1/2 activation in F98 glioma cells. PD98059, a specific inhibitor for ERK activation imitates rhein effects on morphology and expressions of GFAP but did not help to induce any apoptosis or autophagy. Collective data exhibited that potentials of rhein in anti-cancer property in ERK-independent apoptosis and autophagy in association with downregulated ERK-dependent differentiation process of glioma cell lines.

Decreased progranulin levels in patients and rats with subarachnoid hemorrhage: a potential role in inhibiting inflammation by suppressing neutrophil recruitment.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a devastating neurological injury with high morbidity and mortality that is mainly caused by early brain injury (EBI). Progranulin (PGRN) is known to be involved in various biological functions, such as anti-inflammation and tissue repair. This study aimed to investigate the change of PGRN in the brain after SAH and its role on EBI. METHODS: The levels of PGRN, myeloperoxidase (MPO), interleukin1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) were detected in the cerebrospinal fluid (CSF) from SAH patients by enzyme-linked immunosorbent assay (ELISA). In addition, PGRN levels were also detected in the cerebral cortex after experimental SAH in rats by western blotting and immunohistochemistry (IHC). Recombinant human PGRN (r-PGRN) or an equal volume of phosphate-buffered saline (PBS) was administrated at 30 min after SAH. All rats were subsequently sacrificed at 24 h after SAH. Neurological score and brain water content were assessed. For mechanistic studies, the changes of MPO, matrix metalloproteinase-9 (MMP-9), zonula occludens 1 (ZO-1), Bcl-2, and cleaved caspase-3 were examined by western blotting and the levels of pro-inflammatory cytokines (IL-1ß and TNF-α) were determined by ELISA. In addition, neuronal apoptosis and blood brain barrier (BBB) permeability were examined. RESULTS: The levels of PGRN significantly decreased, and the levels of MPO, IL-1ß, and TNF-α were markedly elevated in the CSF from SAH patients. In rats, PGRN levels in the brain also decreased after SAH. Administration of r-PGRN decreased brain water content and improved neurological scores at 24 h after SAH. These changes were associated with marked reductions in MPO, MMP-9, and proinflammation cytokine levels, as well as increased levels of Bcl-2 and ZO-1. In addition, neuronal apoptosis and BBB permeability were alleviated by r-PGRN. CONCLUSIONS: These results indicate that the levels of PGRN decreased after SAH and that r-PGRN alleviates EBI after SAH possibly via inhibition of neutrophil recruitment, providing a new target for the treatment of SAH.

Expression of Cytoplasmic Gelsolin in Rat Brain After Experimental Subarachnoid Hemorrhage.

Convincing evidence indicates that apoptosis contributes to the unfavorable prognosis of subarachnoid hemorrhage (SAH), a significant cause of morbidity and case fatality throughout the world. Gelsolin (GSN) is a Ca(2+)-dependent actin filament severing, capping, and nucleating protein, as well as multifunctional regulator of cell structure and metabolism, including apoptosis. In the present study, we intended to investigate the expression pattern and cell distribution of GSN in rat brain after experimental SAH. GSN expression was examined in sham group and at 3, 6, 12 h, day 1 (1 day), 2, 3, 5, and 7 days after SAH by Western blot analysis as well as real-time polymerase chain reaction. Immunohistochemistry and immunofluorescence were performed to detect the localization of GSN. The level of GSN protein expression was significantly decreased in SAH group and reached a bottoming point on 1 day after SAH. GSN mRNA level was significantly decreased in SAH groups in comparison with the sham group, and reached a minimum value at 12 h after SAH. Immunohistochemistry showed that GSN was constitutively and obviously expressed in the cortex of the normal rat brain and significantly decreased in the rat cortex after SAH. In addition, immunofluorescence results revealed that GSN expression could be found in both neurons and microglias, as well as in glialfibrillary acidic protein-positive astrocytes. The decreased expression of GSN could mainly be found in neurons and astrocytes as well, and GSN-positive microglias showed different cell morphological characteristics. Interestingly, the protein and gene levels of GSN seemed to be constant in the rat hippocampus of sham and SAH groups. These findings suggested a potential role of GSN in the pathophysiology of the brain at the early stage of SAH.

Establishment of swine-penetrating craniocerebral gunshot wound model.

BACKGROUND: Bullet-induced brain wounds are common among military personnel in war zones and among civilians with gun accidents or crime-related gun injuries. The goal of this study was to develop a nonfatal porcine model of penetrating craniocerebral gunshot wound (PCGW) by firing a projectile in live swine to induce PCGW in such a realistic manner as to reconstruct their physical characteristics. MATERIALS AND METHODS: We established a nonfatal porcine model of PCGW based on a custom-designed experimental gun that emulates the shooting of a 5.56-mm NATO standard rifle at 800 m (317 m/s; 200.9 J). Commercial swine (n = 20) were subjected to a ballistic wound to the bilateral frontal lobe, and four swine were used as controls. Surviving swine were used in subsequent first-aid, management, and monitoring experiments for neurosurgeons. Various physiological variables were measured continuously. After computed tomography (CT) scanning and three-dimensional CT reconstructions, all pigs underwent primary lifesaving emergency interventions, including emergency decompressive craniotomies and hemorrhage control. RESULTS: In our nonfatal porcine model of PCGW, injuries were comparable in their morphology to real gunshot wounds, as evidenced by analysis of wound characteristics and CT scan images. The survival rates of the pigs were 100% within 2 h, 95% within 6 h, 85% within 12 h, and 85% within 24 h (P < 0.01). Hemodynamics, hematology, blood routine biochemistry, coagulation, and other physiological parameters also exhibited significant changes in the PCGW pigs. CONCLUSIONS: This model makes possible the laboratory reproduction of real ballistic wounds in a live large animal model that is close to humans.

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.

SIRT1 inhibition by sirtinol aggravates brain edema after experimental subarachnoid hemorrhage.

Secondary brain injury following subarachnoid hemorrhage (SAH) is poorly understood. We utilized a rat model of SAH to investigate whether SIRT1 has a protective role against brain edema via the tumor suppressor protein p53 pathway. Experimental SAH was induced in adult male Sprague-Dawley rats by prechiasmatic cistern injection. Brain SIRT1 protein levels were examined in the sham controls and in rats 6, 12, 24, 48, and 72 hr after SAH induction. The SIRT1 inhibitor sirtinol was administered by intracerebroventricular infusion. Neurological functions, blood-brain barrier (BBB) disruption, and brain water content were assessed. Endothelial cell apoptosis, caspase 3 protein expression, p53 acetylation, and matrix metalloproteinase-9 (MMP-9) activity were examined. Compared with the control, SIRT1 protein expression increased remarkably, reaching a maximum at 24 hr after SAH. Sirtinol treatment significantly lowered SIRT1 expression, accompanied by deteriorated neurologic function, BBB disruption, brain edema, increased endothelial cell apoptosis, and increased MMP-9 gelatinase activity compared with the rats treated with vehicle only. Our results suggest that increased expression of endogenous SIRT1 may play a neuroprotective role against brain edema after SAH.

Inhibition of c-Jun N-terminal kinase ameliorates early brain injury after subarachnoid hemorrhage through inhibition of a Nur77 dependent apoptosis pathway.

Nur77 is a potent pro-apoptotic member of the orphan nuclear receptor superfamily. Our previous study revealed Nur77-mediated apoptotic also involved in early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH). Previous researches show that c-Jun N-terminal kinase (JNK) positively regulates Nur77 nuclear export and apoptosis by phosphorylating Nur77. To determine whether activation of JNK is directly associated with Nur77 dependent apoptosis pathway. We hypothesized that SP600125, a chemical inhibitor of JNK, may effectively ameliorate EBI by inhibiting Nur77 phosphorylation and its transcriptional activity. Hence, in this study was designed to explore the neuroprotective effects of SP600125 in EBI after SAH. Adult male SD rats were randomly assigned to four groups: control; SAH + DMSO; SAH + SP10 and SAH + SP30, a dose of 10 and 30 mg/kg SP600125 was directly administered intraperitoneally 30 min before and 2 h after SAH induction. SP600125 markedly decreased expressions of p-JNK, p-Nur77, Bcl-2, cyto C, caspase-3 and inhibited apoptosis. Improvement of neurological deficit, alleviation of brain edema and amelioration of EBI were obtained after treatment of SP600125. Transferase-mediated dUTP nick end labeling-positive cells were reduced markedly in brain cortex by SP600125. Our studies indicate JNK plays important roles in Nur77 activation. These findings strongly support the hypothesis that SP600125 treatment can ameliorate EBI after experimentally induced SAH by inhibiting a Nur77-dependent apoptotic pathway.

Resveratrol prevents neuronal apoptosis in an early brain injury model.

BACKGROUND: Resveratrol has been shown to attenuate cerebral vasospasm after subarachnoid hemorrhage (SAH); however, no study has explored its neuroprotective effect in early brain injury (EBI) after experimental SAH. The aim of this study was to evaluate the antiapoptotic function of resveratrol in EBI and its relationship with the PI3K/Akt survival pathway. METHODS: Experimental SAH was induced in adult male rats by prechiasmatic cistern injection. Control and SAH rats were divided into six groups and treated with low (20 mg/kg) or high (60 mg/kg) concentrations of resveratrol with or without LY294002 cotreatment. Brain samples of the rats were analyzed by immunohistochemistry, immunofluorescence staining, Western blotting, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assays. RESULTS: High-concentration but not low-concentration resveratrol treatment in SAH rats led to a significant increase in phosphorylated Akt (p-Akt) protein levels compared with SAH rats without treatment. In addition, p-Akt-positive cells mainly colocalized with NeuN-positive cells. Neuronal apoptosis in SAH rat brain was attenuated by high-concentration resveratrol treatment. The antiapoptotic effect of resveratrol in SAH rats could be partially abrogated by the PI3K/Akt signaling inhibitor LY294002. CONCLUSIONS: Our results show that resveratrol has an antiapoptotic effect in EBI and that resveratrol might act through the PI3K/Akt signaling pathway.

Astaxanthin offers neuroprotection and reduces neuroinflammation in experimental subarachnoid hemorrhage.

BACKGROUND: Neuroinflammation has been proven to play a crucial role in early brain injury pathogenesis and represents a target for treatment of subarachnoid hemorrhage (SAH). Astaxanthin (ATX), a dietary carotenoid, has been shown to have powerful anti-inflammation property in various models of tissue injury. However, the potential effects of ATX on neuroinflammation in SAH remain uninvestigated. The goal of this study was to investigate the protective effects of ATX on neuroinflammation in a rat prechiasmatic cistern SAH model. METHODS: Rats were randomly distributed into multiple groups undergoing the sham surgery or SAH procedures, and ATX (25 mg/kg or 75 mg/kg) or equal volume of vehicle was given by oral gavage at 30 min after SAH. All rats were sacrificed at 24 h after SAH. Neurologic scores, brain water content, blood-brain barrier permeability, and neuronal cell death were examined. Brain inflammation was evaluated by means of expression changes in myeloperoxidase, cytokines (interleukin-1ß, tumor necrosis factor-α), adhesion molecules (intercellular adhesion molecule-1), and nuclear factor kappa B DNA-binding activity. RESULTS: Our data indicated that post-SAH treatment with high dose of ATX could significantly downregulate the increased nuclear factor kappa B activity and the expression of inflammatory cytokines and intercellular adhesion molecule-1 in both messenger RNA transcription and protein synthesis. Moreover, these beneficial effects lead to the amelioration of the secondary brain injury cascades including cerebral edema, blood-brain barrier disruption, neurological dysfunction, and neuronal degeneration. CONCLUSIONS: These results indicate that ATX treatment is neuroprotective against SAH, possibly through suppression of cerebral inflammation.

Astaxanthin alleviates early brain injury following subarachnoid hemorrhage in rats: possible involvement of Akt/bad signaling.

Apoptosis has been proven to play a crucial role in early brain injury pathogenesis and to represent a target for the treatment of subarachnoid hemorrhage (SAH). Previously, we demonstrated that astaxanthin (ATX) administration markedly reduced neuronal apoptosis in the early period after SAH. However, the underlying molecular mechanisms remain obscure. In the present study, we tried to investigate whether ATX administration is associated with the phosphatidylinositol 3-kinase-Akt (PI3K/Akt) pathway, which can play an important role in the signaling of apoptosis. Our results showed that post-SAH treatment with ATX could cause a significant increase of phosphorylated Akt and Bad levels, along with a significant decrease of cleaved caspase-3 levels in the cortex after SAH. In addition to the reduced neuronal apoptosis, treatment with ATX could also significantly reduce secondary brain injury characterized by neurological dysfunction, cerebral edema and blood-brain barrier disruption. In contrast, the PI3K/Akt inhibitor, LY294002, could partially reverse the neuroprotection of ATX in the early period after SAH by downregulating ATX-induced activation of Akt/Bad and upregulating cleaved caspase-3 levels. These results provided the evidence that ATX could attenuate apoptosis in a rat SAH model, potentially, in part, through modulating the Akt/Bad pathway.

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 .

Hydrogen-rich saline alleviates early brain injury via reducing oxidative stress and brain edema following experimental subarachnoid hemorrhage in rabbits.

BACKGROUND: Increasing experimental and clinical data indicate that early brain injury (EBI) after subarachnoid hemorrhage (SAH) largely contributes to unfavorable outcomes, and it has been proved that EBI following SAH is closely associated with oxidative stress and brain edema. The present study aimed to examine the effect of hydrogen, a mild and selective cytotoxic oxygen radical scavenger, on oxidative stress injury, brain edema and neurology outcome following experimental SAH in rabbits. RESULTS: The level of MDA, caspase-12/3 and brain water content increased significantly at 72 hours after experimental SAH. Correspondingly, obvious brain injury was found in the SAH group by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) and Nissl staining. Similar results were found in the SAH+saline group. In contrast, the upregulated level of MDA, caspase-12/3 and brain edema was attenuated and the brain injury was substantially alleviated in the hydrogen treated rabbits, but the improvement of neurology outcome was not obvious. CONCLUSION: The results suggest that treatment with hydrogen in experimental SAH rabbits could alleviate brain injury via decreasing the oxidative stress injury and brain edema. Hence, we conclude that hydrogen possesses the potential to be a novel therapeutic agent for EBI after SAH.

Biphasic activation of nuclear factor-kappa B in experimental models of subarachnoid hemorrhage in vivo and in vitro.

It has been proven that nuclear factor-kappa B (NF-κB) is activated as a well-known transcription factor after subarachnoid hemorrhage (SAH). However, the panoramic view of NF-κB activity after SAH remained obscure. Cultured neurons were signed into control group and six hemoglobin- (Hb-) incubated groups. One-hemorrhage rabbit SAH model was produced, and the rabbits were divided randomly into one control group and five SAH groups. NF-κB activity was detected by electrophoretic mobility shift assay (EMSA) and immunohistochemistry. Real-time polymerase chain reaction (PCR) was performed to assess the downstream genes of NF-κB. NeuN immunofluorescence and lactate dehydrogenase (LDH) quantification were used to estimate the neuron injury. Double drastically elevated NF-κB activity peaks were detected in rabbit brains and cultured neurons. The downstream gene expressions showed an accordant phase peaks. NeuN-positive cells decreased significantly in day 3 and day 10 groups. LDH leakage exhibited a significant increase in Hb-incubated groups, but no significant difference was found between the Hb incubated groups. These results suggested that biphasic increasing of NF-κB activity was induced after SAH, and the early NF-κB activity peak indicated the injury role on neurons; however, the late peak might not be involved in the deteriorated effect on neurons.

Combinatorial administration of insulin and vitamin C alleviates the cerebral vasospasm after experimental subarachnoid hemorrhage in rabbit.

BACKGROUND: Cerebral vasospasm (CVS) is a common serious complication after the spontaneous subarachnoid hemorrhage (SAH). Despite recent advances in medical and surgical treatments, the 30-day mortality rate of SAH remains high, and there is lack of especially effective clinical treatment to alleviate and improve CVS. The present study has investigated the therapeutic effect of insulin and vitamin C on CVS after SAH. RESULTS: Five days after SAH, there is obvious basilar artery spasm in SAH group, whose average vascular cross-sectional area (233,099 ± 16,750 µm²) is significantly smaller than that in control group (462,128 ± 74,756 µm²), which is also significantly different from those in SAH + insulin group (221,114 ± 43,457 µm²) and SAH + vitamin C group (237,820 ± 21,703 µm²). SAH + insulin + vitamin C group shows no evident vasospasm and maintains a vascular cross-sectional area of 425,530 ± 45,503 µm², which is significantly different from that in SAH group. Insulin receptor α (InRα) expression is significantly downregulated in the vascular endothelial cells of SAH, SAH + insulin, and SAH + vitamin C groups (P < 0.01) but remains unchanged in vascular endothelial cells of SAH + insulin + vitamin C group (P > 0.05). Five days after SAH, serum and cerebrospinal fluid NO levels in SAH, SAH + insulin, and SAH + vitamin C groups decrease significantly (P < 0.01) compared to that in control group, whereas the reduction is not evident in SAH + insulin + vitamin C group (P > 0.05). CONCLUSION: Combinatorial treatment with insulin and vitamin C has effectively relieved the CVS after SAH in rabbit, possibly through increasing the InRα expression and NO level, whereas treatment with insulin or vitamin C alone fails to do so.

Involvement of endothelial-derived relaxing factors in the regulation of cerebral blood flow.

Despite numerous researches and advances in the present times, delayed cerebral vasospasm remains a severe complication leading to a high mortality and morbidity in patients with subarachnoid hemorrhage (SAH). Since the discovery of endothelium-derived relaxing factor (EDRF) in 1980, its role in delayed cerebral vasospasm after SAH has been widely investigated as well as in regulation of basic cerebral blood flow, pathophysiology of vasoconstriction and application on prevention and treatment of cerebral vasospasm. Among all the EDRFs, nitric oxide has caught the most attention, and the other substances which display similar properties with characteristics of EDRF such as carbon monoxide (CO), hydrogen sulfide (H(2)S), hydrogen peroxide (H(2)O(2)), potassium ion (K(+)) and methane (CH(4)) have also evoked great interest in the research field. This review provides an overview of recent advances in investigations on the involvement of EDRFs in the regulation of cerebral blood flow, especially in cerebral vasospasm after SAH. Possible therapeutic measures and potential clinical implications for cerebral vasospasm are also summarized.

fMRI study of mesial temporal lobe epilepsy using amplitude of low-frequency fluctuation analysis.

Various functional imaging tools have been used to detect epileptic activity in the neural network underlying mesial temporal lobe epilepsy (mTLE). In the present fMRI study, a data-driven approach was employed to map interictal epileptic activity in mTLE patients by measuring the amplitude of low-frequency fluctuation (ALFF) of the blood oxygen level-dependent (BOLD) signal. Twenty-four left mTLE patients and 26 right mTLE patients were investigated by comparing with 25 healthy subjects. In the patients, the regions showing increased ALFF were consistently distributed in the mesial temporal lobe, thalamus, and a few of other cortical and subcortical structures composing a mesial temporal epilepsy network proposed previously, while the regions showing decreased ALFF were mostly located in the areas of so-called default-mode network. Data of simultaneous EEG-fMRI from a portion of the patients suggested that the increases in ALFF might be associated with the interictal epileptic activity. Individual analyses based on statistic parametric mapping revealed a moderate sensitivity and a fairly high specificity for the lateralization of unilateral mTLE. We conclude that the ALFF analysis may provide a useful tool in fMRI study of epilepsy.

Effects of recombinant human erythropoietin (rhEPO) on JAK2/STAT3 pathway and endothelial apoptosis in the rabbit basilar artery after subarachnoid hemorrhage.

Previous studies have shown that recombinant human erythropoietin (rhEPO) can attenuate the degree of cerebral vasospasm following experimental subarachnoid hemorrhage (SAH). However, the mechanisms for this beneficial effect are still poorly understood. SAH-induced endothelial apoptosis may trigger, aggravate, and maintain cerebral vasospasm. We, therefore, tried to analyze whether rhEPO administration influenced the endothelial cell apoptosis in the basilar artery after SAH. Another aim of the current study was to investigate the modulation of rhEPO on the activity of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), which played an important role in the signaling of apoptosis. A total of 48 rabbits were randomly divided into four groups; control group, SAH group, SAH+vehicle group, and SAH+rhEPO group. All SAH animals were subjected to injection of autologous blood into cisterna magna twice on day 0 and day 2. The rhEPO was administered i.p. starting 5 min after the induction of SAH on day 0 and repeated every 8 h for 120 h. The basilar arteries were extracted on day 5 after SAH. As a result, we found that administration of rhEPO could activate JAK2 and STAT3 in the basilar artery and decrease the apoptosis index of endothelial cells following SAH. Moreover, the anti-apoptotic genes such as bcl-2 and bcl-xL were up-regulated after the injections of rhEPO. In conclusion, the therapeutic effect of rhEPO on the subsequent vasospasm after SAH may relate to its inhibition on the endothelial apoptosis in the cerebral arteries, which may be mediated in part by JAK2/STAT3 signaling pathway.

Hemolysate-induced expression of intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 expression in cultured brain microvascular endothelial cells via through ROS-dependent NF-kappaB pathways.

In order to determine the possible effects of hemolysate on brain microvascular endothelial cells (BMECs), we examined the effects of hemolysate on the expression of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1), generation of reactive oxygen species (ROS), and NF-kappaB activation in rat BMECs. Hemolysate induced the expression of ICAM-1 and MCP-1 in endothelial cells. In addition, hemolysate stimulated nuclear translocation of the p65 subunit of NF-kappaB, and NF-kappaB DNA-binding activity in BMECs. Furthermore, hemolysate increased ROS generation, and hemolysate-induced ICAM-1and MCP-1 expression and NF-kappaB activation were abrogated in the presence of the direct scavenger of ROS. Taken together, our results indicate that hemolysate can induce inflammatory responses that increase expression of ICAM-1 and MCP-1, through ROS-dependent NF-kappaB activation in BMECs.

Inhibition of hemolysate-induced iNOS and COX-2 expression by genistein through suppression of NF-small ka, CyrillicB activation in primary astrocytes.

Genistein is a major isoflavone compound from soybean. We investigated the anti-inflammatory properties of genistein in primary astrocytes treated with hemolysate. The results indicated that genistein inhibited the expression of hemolysate induced iNOS and COX-2 mRNA on astrocytes. Furthermore, this compound inhibited the level of hemolysate-stimulated nuclear factor-kappa B (NF-small ka, CyrillicB). Therefore, we suggested that the effect of genistein-mediated inhibition of the expression hemolysate-induced iNOS and COX-2 genes is due to under the suppression of NF-small ka, CyrillicB activation in the transcriptional level.