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To investigate the effects of ischemia/reperfusion on rat submandibular glands without denervation and the possible protective effects of ischemia preconditioning on the glands that experienced ischemia/reperfusion, in-situ ischemia/reperfusion and ischemia preconditioning experimental models of submandibular glands of healthy male Wistar rats were conducted. For ischemia/reperfusion groups, the glands were subjected to 90 min of ischemia without denervation, followed by 1, 12, 24, or 72 h of reperfusion. Ischemia preconditioning was achieved by 3 min of ischemia following 3 min of reperfusion, performed three times before ischemia/reperfusion. Salivary secretion, histological changes, alterations of tight junctions, myeloperoxidase activity, cellular apoptosis, and reactive oxygen species levels were detected. In ischemia/reperfusion glands, rising acute-inflammation responses, reduced tight-junction width, and increased myeloperoxidase activity, reactive oxygen species levels, and apoptotic cell numbers were observed, along with secretory dysfunction, especially at 1 and 12 h post-reperfusion, which seemed to gradually return to normal by 72 h post-reperfusion. In contrast, ischemia preconditioning showed the potential to ameliorate the injury-stress responses caused by ischemia/reperfusion. Our study revealed that ischemia/reperfusion could cause a series of injury-stress responses and ultimately lead to hyposecretion, independently of the parasympathetic nerve supply, which might play an important role in the early-phase dysfunction of the transplanted glands. Ischemia preconditioning could protect the involved glands and improve ischemia/reperfusion-induced hyposecretion.
Subject(s)
Ischemic Preconditioning/methods , Reperfusion Injury/prevention & control , Submandibular Gland/blood supply , Animals , Apoptosis/physiology , Disease Models, Animal , In Situ Nick-End Labeling , Male , Microscopy, Electron, Transmission , Monocytes/pathology , Neutrophils/pathology , Peroxidase/analysis , Random Allocation , Rats , Rats, Wistar , Reactive Oxygen Species/analysis , Saliva/metabolism , Salivary Ducts/pathology , Secretory Rate/physiology , Submandibular Gland/metabolism , Submandibular Gland/pathology , Tight Junctions/pathology , Time FactorsABSTRACT
INTRODUCTION: Our previous study showed that the abscisic acid receptor lanthionine synthetase C-like 2 (LanCL2) is a significant prognostic factor for overall survival in young glioblastoma patients. However, the role of LanCL2 in glioblastoma remains unclear yet. OBJECTIVES: This study aims to investigate the role of LanCL2 in regulating in-vitro cell invasion and in-vivo tumor progression of glioblastoma and its underlying mechanism. METHODS: Tyrosine 198 or 295 residue of LanCL2 was mutated using site-directed mutagenesis to block its phosphorylation. The role of LanCL2 in glioblastoma was investigated using transwell or 3D invasion assay, matrix degradation assay and intracranial xenograft model. RESULTS: This study showed that nuclear transport of LanCL2 was enhanced by overexpression of LanCL2 or its ligand abscisic acid in glioblastoma cells. Knockdown of LanCL2 suppressed migration, invasion and invadopodia formation of glioblastoma cells, whereas overexpression of wild-type LanCL2 enhanced them. Blocking of Tyr295 residue phosphorylation of LanCL2 impeded its nuclear transport, retarded glioblastoma cell motility and invadopodia formation, and deceased the phosphorylation of Cortactin and STAT3. c-Met was identified as the upstream tyrosine kinase of Tyr295 residue of LanCL2, and inhibition of c-Met markedly suppressed the nuclear transport of LanCL2. Moreover, overexpression of wild-type LanCL2 significantly promoted orthotopic tumor growth of glioblastoma in vivo and led to poor survival of mice with median survival time of 33.5 days, whereas Tyr295 mutation rescued it with median survival time of 49 days. CONCLUSION: Our findings suggested that Tyr295 phosphorylation is crucial to the activation and nuclear transport of LanCL2, as well as invadopodia formation and tumor progression of glioblastoma, providing the evidence of a novel signaling axis c-Met/LanCL2/STAT3/Cortactin and the first observation of the importance of Tyr295 phosphorylation to LanCL2.
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Due to its extremely complex pathogenesis, no effective drugs to prevent, delay progression, or cure Alzheimer's disease (AD) exist at present. The main pathological features of AD are senile plaques composed of ß-amyloid, neurofibrillary tangles formed by hyperphosphorylation of the tau protein, and degeneration or loss of neurons in the brain. Many risk factors associated with the onset of AD, including gene mutations, aging, traumatic brain injury, endocrine and cardiovascular diseases, education level, and obesity. Growing evidence points to chronic stress as one of the major risk factors for AD, as it can promote the onset and development of AD-related pathologies via a mechanism that is not well known. The use of murine stress models, including restraint, social isolation, noise, and unpredictable stress, has contributed to improving our understanding of the relationship between chronic stress and AD. This review summarizes the evidence derived from murine models on the pathological features associated with AD and the related molecular mechanisms induced by chronic stress. These results not only provide a retrospective interpretation for understanding the pathogenesis of AD, but also provide a window of opportunity for more effective preventive and identifying therapeutic strategies for stress-induced AD.
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OBJECTIVE: To study the role of neuroglobin (Ngb) in the pathologic process of contusion and laceration of brain in children. METHODS: The proteins in the brain tissue were extracted by two-dimensional gel electrophoresis in 3 children undergoing brain ventricular neoplasms resection (normal brain tissue) and in 8 children with contusion and laceration of brain. The image analysis was done using the PDQuest 7.0 software. The differential protein spots were detected and analyzed with Applied Biosystems Voyager System 4307 MALDI-TOF Mass Spectrometer and bioinformatical skills. Ngb expression in the brain tissue was measured using immunohistochemisty. Ngb expression in plasma was measured using ELISA in 15 children with contusion and laceration of brain and 10 healthy children. RESULTS: Expression maps of the brain tissue were established by two-dimensional gel electrophoresis in children with contusion and laceration of brain and healthy children. Six differential protein spots were found and 5 of them were identified by mass spectrum. Immunohistochemisty assay showed that Ngb expression in the brain tissue in children with contusion and laceration of brain was significantly higher than in normal controls (P<0.05). ELISA results showed that Ngb expression in the plasma increased significantly 6, 12, 18, 24 and 48 hours after trauma in children with contusion and laceration of brain compared with healthy children (P<0.01). CONCLUSIONS: Ngb may play an important role in the pathologic process of contusion and laceration of brain in children.
Subject(s)
Brain Injuries/metabolism , Globins/analysis , Nerve Tissue Proteins/analysis , Adolescent , Child , Electrophoresis, Gel, Two-Dimensional , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunohistochemistry , Male , Neuroglobin , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
Background: Traffic-related pollution is associated with the onset of asthma and the development of different phenotypes of asthma. Few studies have investigated the association between traffic proximity and late-onset of asthma (LOA) and early-onset asthma (EOA). This study was conducted to investigate the associations of LOA phenotypes with a function of the distance between residence and heavy traffic roads (HTRs). Methods: The study group consisted of 280 patients who were (LOA: 78.4%) recruited consecutively from a pay-for-performance asthma program to clarify the patient characteristics and proximity to HTRs within 1,000 m from their residences between EOA and LOA in three urban centers in Taiwan. The subsequent analysis focused on patients with LOA (n = 210) linking phenotypes and distance to HTRs. Results: Subjects with LOA tended to be older than those with EOA and had shorter asthma duration, poorer lung function, lower atopy, and less exposure to fumes or dust at home. Patients with LOA were more likely than those with EOA to live within 900 m of two or more HTRs (14.3 vs. 3.4%, p = 0.02). Among patients with LOA, minimum distance to an HTR was negatively associated with numbers of specific IgE as well as positively associated with the age of onset and body weight significantly. A higher proportion of patients with atopy (26.3 vs. 20.6%, p = 0.001. odds ratio [OR]: 2.82) and anxiety/depression (21.0 vs. 18.1%, p = 0.047. OR: 1.81) and a trend of lower proportion of patients with obese (5.7 vs. 12.4%, p = 0.075) were found to be living within 900 m from HTRs. Conclusions: Late-onset of asthma (LOA) tended to live in areas of higher HTR density compared to EOAs. Among patients with LOA living close to HTRs, the interaction between traffic-related pollution, allergy sensitization, and mood status were the factors associated with asthma onset early. Obesity may be the factor for later onset who live far from HTRs.
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BACKGROUND: As of 2 March, 2020, at least 80 151 coronavirus disease 2019 (COVID-19) cases were reported in China. Most of the patients had a history of visiting Hubei Province or contacting with people who had ever stayed in or passed by Hubei Province or were exposed to symptoms. Some patients got infected through only asymptomatic contact. This study aimed to report the epidemic features and lab identification of a patient confirmed with COVID-19 infection through only asymptomatic contact. CASE PRESENTATION: A 44-year-old man, who lived in Nanchang, Jiangxi Province, China until 6 March 2020, suffered from cough on 27 January 2020. Fever symptoms appeared on 28 January, with a maximum temperature of 38.8 °C, accompanied by cough, sore throat, headache, fatigue, muscle ache, joint ache, and other symptoms. The symptoms continued until he was hospitalized on 30 January. Coronavirus conventional polymerase chain reaction assay was positive for the throat swab sample. The patient, along with his wife and son, drove from Nanchang to back to Honghu City, Hubei Province, on 23 January 2020. After staying with his parents and brother's family for 3 days, the patient drove back to Nanchang and arrived on 25 January. On the way back home, they stopped by Tongshan service area, Hubei Province, without any close contact with other people. After arriving home in Nanchang City, Jiangxi Province, none of them left their residence. In addition, his parents stayed at home for 20 days with his younger brother's family before they got back. His younger brother and one of his brother's children visited Wuhan on 5 January and came home on 6 January 2020. CONCLUSIONS: This report suggested that, in the early phase of COVID-19 pneumonia, routine screening could miss patients who were virus carriers. Highlighting travel history is of paramount importance for the early detection and isolation of severe acute respiratory syndrome coronavirus 2 cases.
Subject(s)
Asymptomatic Infections , Betacoronavirus , Coronavirus Infections/transmission , Pneumonia, Viral/transmission , Adult , COVID-19 , China , Contact Tracing , Coronavirus Infections/diagnosis , Coronavirus Infections/prevention & control , Humans , Male , Pandemics/prevention & control , Pneumonia, Viral/diagnosis , Pneumonia, Viral/prevention & control , SARS-CoV-2 , TravelABSTRACT
OBJECTIVE: To study the diagnosis, surgical treatment and outcome of craniopharyngioma in 31 children. METHODS: The clinical data of 31 children (aged 7-14 years) with craniopharyngioma were studied retrospectively. RESULTS: Headache, visual disorder and growth retardation were main manifestations in the 31 children. The 31 children were definitely diagnosed with craniopharyngioma by CT and MRI. In the 31 cases, 19 (61.3%) underwent total tumor removal, 5 (16.1%) subtotal removal, and 7 (22.6%) partial removal. After tumor removal, transient diabetes insipidus occurred in 19 cases (61.3%) and long-term diabetes insipidus in 3 cases. Six cases (19.4%) presented hypothalamic injuries after surgery. No patient died after surgery. Five patients (16.1%) had recurrent tumor in a mean follow-up of 32.5 months. CONCLUSIONS: The diagnosis of childhood craniopharyngioma may be based on clinical manifestations and CT/MRI examinations. Craniotomy is a preferred surgical treatment. Proper extent of tumor resection should be determined in order to reduce the tumor recurrence and the incidence of postoperative complications.
Subject(s)
Craniopharyngioma/surgery , Pituitary Neoplasms/surgery , Adolescent , Child , Craniopharyngioma/diagnosis , Female , Humans , Magnetic Resonance Imaging , Male , Pituitary Neoplasms/diagnosis , Tomography, X-Ray ComputedABSTRACT
OBJECTIVE: To discuss microsurgery in the treatment of tentorial meningiomas to reduce the operative mortality. METHODS: Clinical data of 32 patients were retrospectively analyzed. The operative approaches and outcomes and postoperative management of tentorial meningiomas were discussed. RESULTS: Of the 32 patients, tumors in 27 patients(84.37%) were removed totally, and 5(15.63%) were removed subtotally. In the 5 patients whose tumors were resected subtotally, 3 patients were related to major sinus, and the other 2 related to adhering compactly to the brain stem invaded by tumors, major vessels, or cranial nerves. CONCLUSION: Total resection can be achieved in most patients with microneurosurgical technique. Proper choice of operative approaches may raise the total removal rate and lower the operative mortality.
Subject(s)
Infratentorial Neoplasms/surgery , Meningeal Neoplasms/surgery , Meningioma/surgery , Microsurgery/methods , Adolescent , Adult , Female , Humans , Male , Middle Aged , Retrospective Studies , Supratentorial Neoplasms/surgery , Treatment OutcomeABSTRACT
Background: Because the pathogenesis of high altitude polycythemia (HAPC) is unclear, the aim of the present study was to explore whether abnormal iron metabolism is involved in the pathogenesis of HAPC and the possible cause. Methods: We examined the serum levels of iron, total iron binding capacity, soluble transferrin receptor (sTfR), ferritin, and hepcidin as well as erythropoietin (EPO) and inflammation-related cytokines in 20 healthy volunteers at sea level, 36 healthy high-altitude migrants, and 33 patients with HAPC. Mice that were exposed to a simulated hypoxic environment at an altitude of 5,000 m for 4 weeks received exogenous iron or intervention on cytokines, and the iron-related and hematological indices of peripheral blood and bone marrow were detected. The in vitro effects of some cytokines on hematopoietic cells were also observed. Results: Iron mobilization and utilization were enhanced in people who had lived at high altitudes for a long time. Notably, both the iron storage in ferritin and the available iron in the blood were elevated in patients with HAPC compared with the healthy high-altitude migrants. The correlation analysis indicated that the decreased hepcidin may have contributed to enhanced iron availability in HAPC, and decreased interleukin (IL)-10 and IL-22 were significantly associated with decreased hepcidin. The results of the animal experiments confirmed that a certain degree of iron redundancy may promote bone marrow erythropoiesis and peripheral red blood cell production in hypoxic mice and that decreased IL-10 and IL-22 stimulated iron mobilization during hypoxia by affecting hepcidin expression. Conclusion: These data demonstrated, for the first time, that an excess of obtainable iron caused by disordered IL-10 and IL-22 was involved in the pathogenesis of some HAPC patients. The potential benefits of iron removal and immunoregulation for the prevention and treatment of HAPC deserve further research.
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OBJECTIVE: To explore microsurgical treatment of giant epidermoid cysts in the central region of the skull base in 36 cases. METHODS: The clinic characteristics and the operation experience about the microsurgical treatment of giant epidermoid cysts in the central region of the skull base were retrospectively analyzed. RESULTS: In the 36 cases, 32 had total removal of the tumor, and the other 4 experienced subtotal removal. Thirteen presented nerve system damage or nerve damage aggravation, but there was no operative mortality. CONCLUSION: According to the epidermoid cyst area, the ratio of total resection can be elevated and the complication can be lowered by suitable approach and microneurosurgical technique.
Subject(s)
Epidermal Cyst/surgery , Microsurgery/methods , Skull Base Neoplasms/surgery , Adult , Female , Humans , Male , Middle Aged , Neurosurgical Procedures , Retrospective Studies , Treatment OutcomeABSTRACT
OBJECTIVE: To explore the effect of the cerebral thrombin preconditioning on the thrombin-induced brain edema, to detect the expression of tumor necrosis factor-alpha (TNF-alpha), and to analyse the relationship between TNF-alpha and the thrombin-induced brain edema. METHODS: Forty SD rats were randomly divided into a ST group and a TT group. The rats received 50 L saline (ST group) or 1 U thrombin infusion (TT group), and received the second infusion (10 U thrombin) 24 h later. The rats were sacrificed at 24 and 72 h after the second infusion in order to examine the changes of brain water and sodium contents as well as the expression of TNF-alpha in the brain. RESULTS: The brain water and sodium contents in the ST group were significantly higher than those on the TT group, and those on the 1st day were higher than those on the 3 th day. The positive expression of TNF-alpha and in the change of water content were identical in the TT group and the ST group. CONCLUSION: Thrombin preconditioning can alleviate the thrombin-induced brain edema. The increase of TNF-alpha expression after thrombin treatment may be related to the thrombin-induced brain edema.
Subject(s)
Brain Edema/metabolism , Brain Edema/therapy , Ischemic Preconditioning , Thrombin/adverse effects , Thrombin/therapeutic use , Animals , Brain/metabolism , Brain Edema/etiology , Male , Rats , Rats, Sprague-Dawley , Thrombin/administration & dosage , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Attention deficit/hyperactivity disorder (ADHD) is one of the most highly heritable psychiatric disorders in childhood. The risk gene mutation accounts for about 60 to 90 % cases. Synaptosomal-associated protein of 25 kDa (SNAP-25) is a presynaptic plasma membrane protein which is expressed highly and specifically in the neuronal cells. A number of evidences have suggested the role of SNAP-25 in the etiology of ADHD. Notably, the animal model of coloboma mouse mutant bears a â¼2-cM deletion encompassing genes including SNAP25 and displays spontaneous hyperkinetic behavior. Previous investigators have reported association between SNPs in SNAP25 and ADHD, and controversial results were observed. In this study, we analyzed the possible association between six polymorphisms (rs3746544, rs363006, rs1051312, rs8636, rs362549, and rs362998) of SNAP25 and ADHD in a pooled sample of ten family-based studies and four case-control studies by using meta-analysis. The combined analysis results were significant only for rs3746544 (P = 0.010) with mild association (odds ratio (OR) = 1.14). And, the meta-analysis data for rs8636, rs362549, and rs362998 are the first time to be reported; however, no positive association was detected. In conclusion, we report some evidence supporting the association of SNAP25 to ADHD. Future research should emphasize genome-wide association studies in more specific subgroups and larger independent samples.
Subject(s)
Attention Deficit Disorder with Hyperactivity/genetics , Genetic Predisposition to Disease , Synaptosomal-Associated Protein 25/genetics , Animals , Genetic Association Studies , Genome-Wide Association Study , Humans , Neurotransmitter Agents/metabolismABSTRACT
Non-functioning pituitary adenomas (NFPAs) are the most frequent pituitary tumors. The elucidation of the mechanisms of aggressive NFPAs in bone destruction is required in order to guide the clinical diagnosis and treatment of NFPAs. In the present study, we investigated the differential proteomics of fibroblasts isolated from clinical specimens of NFPAs with or without bone destruction. Proteomic analysis revealed a group of molecules associated with cytoskeleton organization, including caldesmon, were differentially expressed between fibroblasts isolated from bone destruction NFPAs (BD-NFPAs) and fibroblasts isolated from non-bone destruction NFPAs (NBD-NFPAs). The secreted proteins analysis found that osteopontin was significantly upregulated in BD-NFPAs fibroblasts. Furthermore, immunohistochemical staining of the NFPAs clinical samples showed that the expression of caldesmon in stromal cells and the expression of osteopontin in both tumor cells and stroma were significantly increased in BD-NFPAs. Taken together, our results indicate a possible way that osteopontin secreted from both NFPA cells and surrounding fibroblasts modify caldesmon expression and polymerization in fibroblasts, which may contribute to bone destruction in NFPA patients.
Subject(s)
Adenoma/metabolism , Bone and Bones/metabolism , Calmodulin-Binding Proteins/metabolism , Fibroblasts/metabolism , Osteopontin/metabolism , Pituitary Neoplasms/metabolism , Adenoma/diagnostic imaging , Adenoma/pathology , Adult , Bone and Bones/pathology , Cells, Cultured , Female , Fibroblasts/pathology , Gene Expression Regulation , Humans , Male , Middle Aged , Pituitary Neoplasms/diagnostic imaging , Pituitary Neoplasms/pathology , Polymerization , Proteome , Stromal Cells/metabolism , Stromal Cells/pathologyABSTRACT
OBJECTIVE: To investigate the clinical significance of urinary epidermal growth factor (EGF) in patients with brain tumors. METHODS: The levels of EGF in urine samples collected from 20 patients (9 low grade astrocytomas, 6 anaplastic astrocytomas, and 5 meningiomas) and 5 healthy individuals were determined. EGF levels were measured by radioimmunoassay technique. A preoperative and one postoperative determination were performed. RESULTS: Preoperative urinary EGF levels of astrocytoma patients were statistically higher than those of meningioma patients and the controls (P < 0.01). Preoperative urinary EGF levels showed a positive correlation with the degree of malignance in the astrocytoma patients (P < 0.05). A significant decrease of the postoperative levels of EGF was observed in the astrocytoma patients who underwent gross total resection (P < 0.01). The pre/postoperative urinary EGF levels of the meningioma patients showed no significant fluctuations and showed no significant difference with those of healthy individuals (P > 0.05). CONCLUSION: The urinary EGF levels of astrocytoma patients correlate with the WHO grade of malignance and significantly decrease after gross total removal. Urinary EGF may be of practical value in diagnosing and evaluating the surgical efficacy of astrocytomas.
Subject(s)
Astrocytoma/urine , Biomarkers, Tumor/urine , Brain Neoplasms/urine , Epidermal Growth Factor/urine , Adolescent , Adult , Aged , Female , Humans , Male , Meningioma/urine , Middle AgedABSTRACT
OBJECTIVE: To evaluate the outcome of gamma knife for prolactinomas. METHODS: Eighty-nine patients were treated by gamma knife and 51 were followed up. The dose to the tumor margin ranged from 18 Gy to 35 Gy (mean 26.1 Gy). The maximum radiation dose varied from 36 Gy to 60 Gy (mean 50.41 Gy). The mean tumor diameter was 15.5 mm (5 - 26 mm). RESULTS: The follow-up data were available for 51 patients ranging from 6 to 108 months (mean 37 months). The tumor growth control rate was 100%. The endocrinological remission rate was 40%. The rate of hypopituitarism was 17.6%. CONCLUSION: Gamma knife radiosurgery can be used as a primary treatment for selected prolactinomas,especially for pituitary microadenomas.
Subject(s)
Hypophysectomy/methods , Pituitary Neoplasms/surgery , Prolactinoma/surgery , Radiosurgery/instrumentation , Adolescent , Adult , Female , Follow-Up Studies , Humans , Hypopituitarism/etiology , Male , Middle Aged , Radiosurgery/adverse effects , Treatment OutcomeABSTRACT
OBJECTIVE: To summarize the mononostril-septum-transsphenoidal approach for pituitary adenoma. METHODS: The clinical features, operative techniques, and outcome of 36 patients with pituitary adenoma were analyzed retrospectively. RESULTS: Tumors were totally removed in 28 cases, and subtotally resected in 8 patients. No patient died after the operation. Endocrine symptom of 31 patients returned to the normal level, the symptom of the other 5 cases were improved. Thirty patients with visual field defects recovered after the operation. Cerebrospinal fluid leakage occurred in one patient, and was cured with conservative treatment in 2 weeks. CONCLUSION: Mononostril-septum-transsphenoidal approach can make use of the natural space of the nasal cavity, which has many advantages, such as direct approach, short operative time, minimal invasion, and few complications. It is a effective transsphenoidal surgical approach.
Subject(s)
Adenoma/surgery , Nasal Septum/surgery , Pituitary Neoplasms/surgery , Sphenoid Sinus/surgery , Adult , Female , Humans , Male , Middle Aged , Neurosurgical Procedures/methodsABSTRACT
Stress is an important risk factor of Alzheimer's disease (AD). It has been evidenced that stress could induce tau phosphorylation and increase tau insolubility in brain; however, little is known about the interactional effect of stress with aging on tauopathy. Therefore, we explored the effects of aging on stress-induced tauopathy and the potential mechanism in mouse model of chronic restraint stress (CRS). Here we found that in general, the level of phosphorylated tau (P-tau) was higher in brain of middle-aged mice than that in adult mice under physiological conditions. CRS-induced tau phosphorylation and its insolubility were more prominent in middle-aged mice. The increase of AT8-labeled insoluble P-tau was dramatic in middle-aged mice, which was highly ubiquitinated but did not form PHF structures. The levels of chaperones were relatively lower in middle-aged mice brain; CRS further reduced the expression, especially for HDJ2/HSP40. CRS also suppressed the expression of Pin1, the peptidylprolyl cis/trans isomerase, in middle-aged mice but not in adult mice. Downregulation of HSP40 or Pin1 caused an increase of transfected extraneous tau in 293 cells. Rosmarinic acid (RA) could effectively suppress the elevation of P-tau and insoluble P-tau formation induced by CRS, and reversed the abnormal changes of chaperones and Pin1 particularly in middle-aged mice. Taken together, our findings provided evidence that aging could be a promoting factor in stress-induced tauopathy, which was relevant with malregulation of chaperones and Pin1, and RA might be a promising beneficial agent for stress-induced tauopathy.
Subject(s)
Aging , Antioxidants/therapeutic use , Brain/drug effects , Cinnamates/therapeutic use , Depsides/therapeutic use , Stress, Psychological/drug therapy , Stress, Psychological/metabolism , tau Proteins/metabolism , Animals , Brain/metabolism , Brain/ultrastructure , Corticotropin-Releasing Hormone/metabolism , Disease Models, Animal , HEK293 Cells , HSP90 Heat-Shock Proteins/metabolism , Humans , Male , Mice , Mice, Inbred C57BL , Microscopy, Immunoelectron , NIMA-Interacting Peptidylprolyl Isomerase , Peptidylprolyl Isomerase/metabolism , Phosphorylation , Precipitating Factors , Receptors, Corticotropin/metabolism , Restraint, Physical/adverse effects , Stress, Psychological/etiology , Stress, Psychological/pathology , Transfection , Rosmarinic AcidABSTRACT
OBJECTIVE: To assay the changes of polyamine oxidase (PAO) activities and polyamine levels in the cortex and subcortex at different time of reperfusion following 2 h focal cerebral ischemia in rats in order to explore the regularity and signifiance ofh these changes. METHODS: Rats of 2 h reversible focal cerebral ischemia were produced by ameliorated method of Longa's intraluminal suture occlusion of middle cerebral artery (MCA). PAO activities and polyamine levels in the cortex and subcortex were measured by homovanillic acid fluorometry and high-performance liquid chromatograph (HPLC) after 2, 4, 8, and 24 h reperfusion following 2 h ischemia, respectively. RESULTS: PAO activity of the experimental group increased after 8 h reperfusion (P < 0.01). The peak value of PAO activity appeared after 24 h reperfusion (P < 0.01). Putrescine level of the experimental group was elevated after 4 h reperfusion (P < 0.05), and the peak value of putrescine appeared after 24 h reperfusion (P < 0.05). Spermidine and spermine levels of 8, 24 h reperfusion in the experiment group decreased significantly c eompared with the control group (P < 0.05). CONCLUSION: PAO activities increased significantly after reperfusion following transient focal cerebral ischemia, which promoted the later peak production of putrescine. It may be contributed to the brain damage after cerebral ischemia.
Subject(s)
Ischemic Attack, Transient/metabolism , Oxidoreductases Acting on CH-NH Group Donors/metabolism , Polyamines/metabolism , Reperfusion Injury/metabolism , Animals , Cerebral Cortex/metabolism , Male , Random Allocation , Rats , Rats, Sprague-Dawley , Polyamine OxidaseABSTRACT
OBJECTIVE: To explore the mechanism of alpha-difluoromethylornithine (DFMO) inhibiting ODC activity in the cortex and hippocampus in rats. METHODS: Forty male rats was randomly divided into ischemal control group and DFMO pretreatment group. DFMO was given intravenously half an hour before global cerebral ischemia, and expression of ODC mRNA was measured by comparative reverse transcription-polymerase chain reaction (RT-PCR) in the cortex and hippocampus in rats after 2, 4, 6 h and 8 h of reperfusion. The variations of the expression of ODC mRNA were studied in the DFMO pretreatment group and the ischemal control group respectively. RESULTS: After 2, 4 and 6 h of reperfusion, the expression of ODC mRNA in the cortex and hippocampus in the pretreatment group was lower than that in the ischemia control group significantly (P <0.05, P <0.01), but not at 8 h reperfusion (P > 0.05). CONCLUSION: DFMO suppressed the expression of ODC mRNA after different lengths of reperfusion following 10-minute global cerebral ischemia in rats and it may be one of the ways for DFMO to inhibit ODC activity.
Subject(s)
Brain Ischemia/metabolism , Eflornithine/pharmacology , Ornithine Decarboxylase/biosynthesis , Reperfusion Injury/metabolism , Animals , Cerebral Cortex/metabolism , Hippocampus/metabolism , Male , Ornithine Decarboxylase/genetics , Ornithine Decarboxylase Inhibitors , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Random Allocation , Rats , Rats, Sprague-DawleyABSTRACT
The aim of this retrospective, multicenter clinical study was to evaluate the aetiology of epilepsy in surgically treated patients in China. The detailed clinical records of all intractable partial epilepsy (IPE) were reviewed in five tertiary referral centres from June 1991 to June 2000. 1650 patients (927 males, 723 females) were recruited. 41.4% had aetiological factors, including the histories of major brain trauma (20.9%), febrile seizure (6.5%), meningitis (5.4%), encephalitis (5.0%), prenatal distress (2.1%), birth trauma (0.8%) and family history of seizure (0.7%). The pathological lesions were divided into eight groups according to the nature of the lesion: scar (19.2%), vascular malformations (VM) (17.7%), hippocampal sclerosis (HS) (16.2%), tumours (15.0%), gliosis (12.1%), neuronal migration disorders (NMDs) (7.4%), intracranial infection (4.5%), and other lesions (7.9%). In conclusion, effective management of these aetiological factors and pathological lesions may be essential to deal with IPE. Scar, HS, VM, NMDs are the most likely consequences of antecedent morbid events.