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1.
《Sleep medicine》2013,14(12):1272-1276
BackgroundNarcolepsy is a neuropsychiatric disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and abnormal rapid eye movement (REM) sleep. Tumor necrosis factor α (TNF α) and its cognate receptors have been reported to be involved in the pathophysiology of narcolepsy in addition to the HLA antigen system. Our study aimed to determine if the TNF-α system was associated with narcolepsy in our patients.MethodsWe first measured the plasma level of TNF α in 56 narcoleptic patients and 53 control subjects using a highly sensitive enzyme-linked immunosorbent assay. We next determined the genotype of three single nucleotide polymorphisms (SNPs) (T-1031C, C-863A, and C-857T) at the promoter region of the TNF-α gene and one missense SNP (T587G, M196R) at the exon 6 of the tumor necrosis factor receptor 2 gene, TNFR2, in a sample of 75 narcoleptic patients and 201 control subjects by direct sequencing analysis.ResultsWe found a significant elevation of plasma level of TNF α in patients with narcolepsy compared with the control subjects (4.64 pg/mL vs 1.06 pg/mL; P = .0013). However, we did not find significant differences between these two groups in the allelic and genotypic distributions of the investigated polymorphisms.ConclusionsOur study suggests that an increased TNF-α level was associated with narcolepsy in our patients, and that chronic inflammation due to various factors might have led to the increased TNF-α levels found in our patients. 相似文献
2.
《Journal of neuroimmunology》1995,61(2):205-212
The kinetics of mRNA expression in the central nervous system (CNS) for a series of putatively disease-promoting and disease-limiting cytokines during the course of experimental autoimmune encephalomyelitis (EAE) in Lewis rats were studied. Cytokine mRNA-expressing cells were detected in cryosections of spinal cords using in situ hybridization technique with synthetic oligonucleotide probes. Three stages of cytokine mRNA expression could be distinguished: (i) interleukin (IL)-12, tumor necrosis factor (TNF)-β (=lymphotoxin-α) and cytolysin appeared early and before onset of clinical signs of EAE; (ii) TNF-α peaked at height of clinical signs of EAE; (iii) IL-10 appeared increasingly at and after clinical recovery. The early expression of IL-12 prior to the expression of interferon-γ (IFN-γ) mRNA shown previously is consistent with a role of IL-12 in promoting proliferation and activation of T helper 1 (Th1) type cells producing IFN-γ. The TNF-β mRNA expression prior to onset of clinical signs favours a role for this cytokine in disease initiation. A pathogenic effector role of TNF-α was suggested from these observations that TNF-α mRNA expression roughly paralleled the clinical signs of EAE. This may be the case also for cytolysin. IL-10-expressing cells gradually increased to high levels in the recovery phase of EAE, consistent with a function in down-regulating the CNS inflammation. From these data we conclude that there is an ordered appearance of putative disease-promoting and -limiting cytokines in the CNS during acute monophasic EAE. 相似文献
3.
While pharmaceutical options remain the overwhelmingly accepted treatment of choice for neurological and psychiatric diseases,
significant accomplishments in regenerative neuroscience research have demonstrated the potential of cellular and synaptic
functional repair in future therapies. Parkinson’s disease stands out as an example in which repair by dopaminergic neurons
appears a viable potential therapy. This article describes the basic neurobiological underpinnings of the rationale for cell
therapy for Parkinson’s disease and the challenges ahead for the use of regenerative medicine in the treatment for this disease. 相似文献
4.
Objective Inflammatory cytokines play important roles in the pathophysiology of cerebral infarction and other central nervous system diseases.This study was designed to investigate the influence of progesterone on lipopolysaccharide-induced expression of tumour necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) in primary cultured microglia.Methods Microglia were obtained from cerebral cortexes of neonatal Sprague Dawley rats.Microglia were separated,purificated, cultured and activated.ELISA was used to detect the level of TNF-α, IL-1β in supernate fluid before and after induced with lipopolysaccharide (LPS) or influenced by progesterone.Results LPS strongly induced the expression of TNF-α, IL-1β in microglia from cerebral cortexes.Progesterone inhibited the expression of TNF-α, IL-1β.Conclusion progesterone significantly reduced the expression of inflammatory factors generated by microglia and inhibited the activation of microglia in vitro. 相似文献
5.
V. V. Safandeev A. A. Kolacheva D. E. Ivanov M. V. Ugryumov 《Neurochemical Journal》2017,11(4):290-295
The most important component of the pathogenesis of Parkinson’s disease is the degradation of the nigrostriatal dopaminergic system, which is a key link in the regulation of motor function. Impaired motor function, and, consequently, the possibility of diagnosing the disease, occur only 20–30 years after the onset of the pathological process with the death of 50–60% of dopaminergic neurons and a decrease in the level of synthesis of dopamine in the striatum by 70–80%. The lack of effective therapy is associated with the late diagnosis of the disease, when there are practically no targets for pharmacotherapy. Therefore, one of the most important priorities of modern neurology is the development of a method for the early diagnosis of Parkinson’s disease at the preclinical (asymptomatic) stage. In this work, a new approach was developed to assess the functional deficiency of the dopaminergic nigrostriatal system using an inhibitor of dopamine-α-methyl-p-tyrosine synthesis in a chronic model of the preclinical stage of Parkinson’s disease in mice. Administration of α-methyl-p-tyrosine to animals in a model of the preclinical stage of Parkinson’s disease led to the appearance of motor behavior disorders but not in the control group. These data point to the possibility of using this approach as a provocative test for the diagnosis of this disease at the preclinical stage, which will allow us to begin treatment aimed at slowing the death of dopaminergic neurons. 相似文献
6.
Bone morphogenic protein-7 (BMP7) is a multifunctional cytokine with demonstrated neurogenic potential. Oligodendrocytes (OLs) death after spinal cord injury (SCI) contributes to demyelination of spared axons, even leading to a permanent neurological deficit. Therefore, therapeutic approaches to prevent OLs death after SCI should be considered. Since the effects of BMP7 on OLs after injury are largely unknown, we demonstrated the effects of BMP7 on TNF-α-induced OLs apoptosis in vitro. The effects of BMP7 on TNF-α-induced OLs apoptosis were verified by flow cytometry, spectrophotometry and western blotting on primary cultures from spinal cord of postnatal day 1 (P1) to P2 rats. As shown by flow cytometry, apoptosis rate was 25.6% for the control group, 59.0% for the TNF-α group, and 33.5% for the BMP7 + TNF-α group; spectrophotometry showed caspase-3 and caspase-8 activity were significantly increased in the TNF-α group than in the control group, and BMP7 could reverse the increase. The involvement of cIAP1 in the protection of BMP7 was determined by western blotting and silencing cIAP1. In summary, our results demonstrated that BMP7 could potently inhibite TNF-α-induced OLs apoptosis and identified the cIAP1 expression level, the activity of caspase-3 and caspase-8 as important mediators of OLs survival after cellular stress and cytokine challenge. 相似文献
7.
McDonnell GV Kirk CW Middleton D Droogan AG Hawkins SA Patterson CC Graham CA 《Journal of neurology》1999,246(11):1051-1058
Allelic association studies with microsatellite markers around the tumour-necrosis factor (TNF) genes have demonstrated significantly
different allele distributions of TNF markers (a and b) between relapsing-remitting/secondary progressive multiple sclerosis
(MS) (RR/SPMS) patients and normal controls. Considering the suspected genetic and immunological heterogeneity in MS, we tested
this association in primary progressive MS (PPMS) patients. Elevated levels of serum soluble TNF receptors (sTNF-R) are reported
in patients with gadolinium enhancing lesions, and animal models suggest a possible therapeutic role of sTNF-RI in MS. Thus
we performed similar association studies using markers for the TNF-R genes. Gene association studies were carried out on 199–216
normal controls, 174 RR/SPMS patients and 102 PPMS patients using polymorphic dinucleotide repeat TNF markers (a, b and d),
and separate markers for TNF-RI and TNF-RII. Forward primers were fluorescently labelled, polymerase chain reaction (PCR)
products were analysed on a fluorescent fragment analyser, and Genescan 672 software was used for allele sizing. Samples were
typed for HLA-DR antigens using PCR technology and sequence-specific oligonucleotide probes. TNFa marker allele distributions
differed significantly between PPMS patients and controls (P = 0.028), largely attributable to an increase in the 118-bp TNFa allele in PPMS patients (P = 0.00024). Allele distributions were similar in PPMS and RR/SPMS patients (P = 0.91). Logistic regression analysis, however, indicated that these associations were not independent of that with HLA-DRB1*15.
For the TNFb marker, the 127-bp allele showed association with both patient categories (PPMS vs. controls, P = 0.010; RR/SPMS vs. controls, P = 0.027), whilst the 128-bp allele occurred more frequently in controls (PPMS vs. controls, P = 0.036: RR/SPMS vs. controls, P = 0.0009). As with the TNFa 118 bp allele, the association with TNFb was not independent of the HLA association. No association
occurred with the TNFd marker, and there were also no significant differences in allele frequencies between MS groups and
controls regarding the marker for TNF-RI or TNF-RII. In Northern Irish patients the TNF contribution to MS genetic susceptibility
is therefore similar across the clinical spectrum of the disease but is not independent of the association with HLA-DRB1*15.
Received: 3 December 1999 Received in revised form: 30 April 1999 Accepted: 14 May 1999 相似文献
8.
Summary Human recombinant tumor necrosis factor- (rTNF-) was administered to normal Fischer 344 rats by stereotaxic intracerebral (IC) injection. Animals received a single injection of either 6×104 UrTNF- or excipient in their right parietal lobe. Others received three consecutive daily injections of either 6×104 U rTNF- or excipient to examine effects of higher accumulative doses. Histological examination of the brain revealed that both single and multiple IC injections of rTNF- triggered an immigration of circulating leukocytes into the site of TNF- injection. After one injection, this cell population was composed mainly of macrophages and neutrophils. Maximal leukocytic influx occurred by 48 h and was composed mostly of neutrophils which were limited to the injection site and perivascular space. Quantitation of the inflammatory reaction by measurement of tissue myeloperoxidase levels supported these histological observations. One day after multiple rTNF- injections, leukocytic adhesion to endothelium, vascular cuffing and leukocytic infiltration into the neuropil was observed at levels comparable to those seen 3 days following a single rTNF- injection. We conclude that while one or more IC injection(s) of 6×104 U rTNF- was well tolerated in normal rats, at this dose the cytokine triggers a pronounced leukocytic infiltration at the site of injection. These results support a role for TNF- as a mediator in inflammatory responses within the central nervous system.Supported in part by a grant from the A. D. Williams Research Fund and by gifts from the Kellogg Foundation, the Lind Lawrence Fund, and the family and friends of Christine Armstrong, Jack Harvey, Christopher Wemple, and Pearl Ylonen. 相似文献
9.
Recent progress in the field of experimental genetics, which enables the selective and conditional ablation or dysregulation in the expression of specific genes in mice, and its application to the study of experimentally inducible models for human disease, have contributed enormously to our understanding of the molecules and mechanisms that underlie autoimmunity and inflammation in the CNS. This article describes the lessons learned from the application of such technology to the study of the tumor necrosis factor-alpha (TNF) ligand/receptor system in the CNS. Important roles for TNF and its two membrane-bound receptors in the initiation and support of CNS inflammation, the development of CNS autoimmunity, and possibly in the resolution of T-cell-mediated disease, as well as their implications for our understanding of the "normal" cellular and molecular mechanisms that underlie CNS pathology, are discussed. 相似文献
10.
INTRODUCTIONAs a kind of endocrine hormone, estradiol plays an important role innervous system[1-14]. Recent researches have indicated that estradiolhas protective effect on the various damages of nervous system andneurotoxicity induced by neurotoxic subs… 相似文献
11.
M. Mäurer N. Kruse R. Giess K. Kyriallis K. V. Toyka P. Rieckmann 《Journal of neurology》1999,246(10):949-954
Tumor necrosis factor-α (TNFα) is a pluripotent proinflammatory cytokine and is thought to play an important role in the inflammatory
process of multiple sclerosis (MS). A G→A transition in the TNFα promotor at position –308 (TNF2 allele) has been shown to be associated with increased TNFα production. This study was designed to detect wether the TNF2 allele is associated with disease progression in MS. We examined the TNFα–308 polymorphism with an allelic discrimination
PCR to detect the G→A transition in the genomic DNA of 283 MS patients from Germany and in 72 patients with amyotrophic lateral
sclerosis (ALS) and 66 with stroke from the same genetic background who served as controls. Disease severity was defined by
the progression index (PI) and by progression to the important clinical landmarks of Extended Disability Status Score (EDSS)
3.5 and 6. In addition, we evaluated the TNFα mRNA expression in whole blood with quantitative PCR. No differences were found
between the presence of the TNF2 allele in MS, ALS, or stroke patients. Among the MS patients the TNF2 allele was not associated with a certain disease course. No association was found between the accumulation of neurological
deficits and progression to clinical landmarks. Although MS patients with the TNF2 allele tended to progress more rapidly from EDSS 3.5 to EDSS 6 this difference was nonsignificant (P = 0.2). Nevertheless, we observed significantly higher TNFα mRNA expression in blood cells of stable patients carrying the
TNF2-allele in comparison to the group with the wild type (P = 0.024). To examine the effect of genetic background we examined the DNA of 60 MS patients and 20 healthy controls in a
Cypriot population of Greek origin. There was a significantly lower frequency of the TNF2 allele in the Cyprus population than in Germans (P = 0.01). No significant differences were found between the frequencies of the TNF2 allele in Cypriot MS patients and controls. Although the TNF2 allele is associated with higher TNFα mRNA baseline levels, our data indicate that this allele appears not to contribute
to MS susceptibility or severity. In addition our data demonstrate that the TNFα–308 polymorphism is segregated differentially
in two European populations of different genetic origin.
Received: 30 November 1998 Received in revised form: 8 April 1999 Accepted: 13 May 1999 相似文献
12.
Acute exercise in mice induces intestinal lymphocyte (IL) apoptosis. Freewheel running reduces apoptosis and forced exercise training increases splenocyte antioxidant levels. The purpose of this study was to examine the effect of freewheel running and acute exercise on mouse IL numbers and concentrations of apoptosis and antioxidant proteins and pro-inflammatory cytokines in IL. Female C57BL/6 mice had access to in-cage running wheels (RW) or cages without wheels (NRW) for 16 weeks and were randomized at the end of training to no exercise control (TC) or to treadmill exercise with sacrifice after 90 min of running (TREAD; 30 min, 22 m min?1; 30 min, 25 m min?1; 30 min, 28 m min?1; 2° slope). IL were analyzed for pro-(caspase 3 and 7) and anti-(Bcl-2) apoptotic proteins, endogenous antioxidants (glutathione peroxidase: GPx; catalase: CAT) and the pro-inflammatory cytokine, TNF-α. RW mice had higher cytochrome oxidase (p < 0.001) and citrate synthase (p < 0.01) activities in plantaris and soleus muscles and higher GPx and CAT expression in IL (p < 0.05) (indicative of training) compared with NRW mice. TNF-α expression was lower (p < 0.05) and IL numbers higher (p < 0.05) in RW vs. NRW mice. No training effect was observed for apoptotic protein expression, although TREAD resulted in higher caspase and lower Bcl-2. These results suggest that freewheel running in mice for 16 weeks enhances antioxidant and reduces TNF-α expression in IL but does not reduce pro-apoptotic protein expression after acute exercise. Results are discussed in terms of implications for inflammatory bowel diseases where apoptotic proteins and TNF-α levels are elevated. 相似文献
13.
Background
Histamine is classified as an inflammatory mediator and has been reported to have anti- as well as pro-inflammatory properties. The aim of this study was to explore the role of histamine on the production of LPS-induced tissue factor (TF) activity and TNFα in monocytes of whole blood in the absence and presence of TNFα or PMA.Methods
Human blood anticoagulated with Fragmin was subjected to stimulation by LPS in the presence and absence of TNFα or PMA and various concentrations of histamine. Tissue factor (TF) activity was measured in lyzed cells after isolation of mononuclear cells whereas TNFα was quantified in plasma after centrifugation of cells.Results
Histamine gave a dose dependent inhibitory effect on LPS-induced TF activity in monocytes of whole blood, with a 50% reduction at 0.033 μM. A similar effect was seen when the blood cells were stimulated with the combination of LPS and TNFα although TNFα enhanced LPS-induced TF activity almost two fold. In contrast, when blood was incubated with LPS and PMA in whole blood, histamine gave a significant rise in TF activity at 0.01 μM and 0.33 μM histamine. The effect of histamine was less at 0.1 μM or higher concentrations giving a biphasic profile. Contrary to the effect of histamine on LPS plus PMA induced TF activity, histamine caused a significant reduction in TNFα albeit less than in the absence of PMA. Intake of aspirin caused a significant rise in LPS-induced TF activity that was almost abolished by histamine at 0.033 μM.Conclusion
Our study shows that histamine has an anti-inflammatory effect on LPS and LPS/TNFα stimulated monocytes of whole blood. In contrast when blood cells are activated by a combination of LPS and PMA whereby PKC is activated, histamine has a procoagulant/pro-inflammatory effect through enhancement of TF activity expression. 相似文献14.
A C Easton A Lourdusamy M Havranek K Mizuno J Solati Y Golub T-K Clarke H Vallada R Laranjeira S Desrivières G H Moll R M?ssner J Kornhuber G Schumann K P Giese C Fernandes B B Quednow C P Müller 《Translational psychiatry》2014,4(10):e457
Although addiction develops in a considerable number of regular cocaine users, molecular risk factors for cocaine dependence are still unknown. It was proposed that establishing drug use and memory formation might share molecular and anatomical pathways. Alpha-Ca2+/calmodulin-dependent protein kinase-II (αCaMKII) is a key mediator of learning and memory also involved in drug-related plasticity. The autophosphorylation of αCaMKII was shown to accelerate learning. Thus, we investigated the role of αCaMKII autophosphorylation in the time course of establishing cocaine use-related behavior in mice. We found that αCaMKII autophosphorylation-deficient αCaMKIIT286A mice show delayed establishment of conditioned place preference, but no changes in acute behavioral activation, sensitization or conditioned hyperlocomotion to cocaine (20 mg kg−1, intraperitoneal). In vivo microdialysis revealed that αCaMKIIT286A mice have blunted dopamine (DA) and blocked serotonin (5-HT) responses in the nucleus accumbens (NAcc) and prefrontal cortex after acute cocaine administration (20 mg kg−1, intraperitoneal), whereas noradrenaline responses were preserved. Under cocaine, the attenuated DA and 5-HT activation in αCaMKIIT286A mice was followed by impaired c-Fos activation in the NAcc. To translate the rodent findings to human conditions, several CAMK2A gene polymorphisms were tested regarding their risk for a fast establishment of cocaine dependence in two independent samples of regular cocaine users from Brazil (n=688) and Switzerland (n=141). A meta-analysis across both samples confirmed that CAMK2A rs3776823 TT-allele carriers display a faster transition to severe cocaine use than C-allele carriers. Together, these data suggest that αCaMKII controls the speed for the establishment of cocaine''s reinforcing effects. 相似文献
15.
During cerebral ischemia, elevation of TNF-α and glutamate to pathophysiological levels in the hippocampus may induce dysregulation of normal synaptic processes, leading ultimately to cell death. Previous studies have shown that patients subjected to a mild transient ischemic attack within a critical time window prior to a more severe ischemic episode may show attenuation in the clinical severity of the stroke and result in a more positive functional outcome. In this study we have investigated the individual contribution of pre-exposure to TNF-α or glutamate in the development of 'ischemic tolerance' to a subsequent insult, using organotypic hippocampal cultures. At 6 days in vitro (DIV), cultures were exposed to an acute concentration of glutamate (30 μM) or TNF-α (5 ng/ml) for 30 min, followed by 24h recovery period. We then examined the effect of the pretreatments on calcium dynamics of the cells within the CA region. We found that pretreatment with TNF-α or glutamate caused in a significant reduction in subsequent glutamate-induced Ca(2+) influx 24h later (control: 100.0 ± 0.8%, n=7769 cells; TNF-α: 76.8 ± 1.0%, n=5543 cells; glutamate: 75.3 ± 1.4%, n=3859 cells; p<0.001). Antagonism of circulating TNF-α (using infliximab, 25 μg/ml), and inhibition of the p38 MAP kinase pathway (using SB 203580, 10 μM) completely reversed this effect. However glutamate preconditioning did not appear to be mediated by p38 MAP kinase signalling, or NMDAR activation as neither SB 203580 nor D-AP5 (100 μM) altered this effect. Glutamate and TNF-α preconditioning resulted in small yet significant alterations in resting Ca(2+) levels (control: 100.0 ± 0.9%, n=2994 cells; TNF-α: 109.7 ± 1.0%, n=2884 cells; glutamate; 93.3 ± 0.8%, n=2899 cells; p<0.001), TNF-α's effect reversed by infliximab and SB 203580. Both TNF-α and glutamate also resulted in the reduction of the proportion (P) of responsive cells within the CA region of the hippocampus (control; P=0.459, 0.451 ≤ x ≥ 0.467, n=14,968 cells, TNF-α; P=0.40, 0.392 ≤ x ≥ 0.407, n=15,218; glutamate; P=0.388, 0.303 ≤ x ≥ 0.396, n=13,919 cells), and in the depression of the frequency of spontaneous Ca(2+) events (vs. control: TNF-α: p>0.00001, D=0.0454; glutamate: p>0.0001, D=0.0534). Our results suggest that attenuation in resting Ca(2+) activity and Ca(2+) related responsiveness of cells within the CA region as a result of glutamate or TNF-α pre-exposure, may contribute to the development of ischemic tolerance. 相似文献
16.
BACKGROUND: Lots of evidences have demonstrated that acute inflammatory reaction plays an important role in cerebral ischemia and cerebral ischemia/reperfusion injury. Tumor necrosis factor (TNF), as one of important inflammatory cytokines, also participates in the injury.
OBJECTIVE: To observe the changes in TNF-α expression and myeloperoxidase (MPO) activity of mouse models of local cerebral infarction induced by photochemical method, and analyze the correlation of TNF-α expression and MPO activity.
DESIGN: Randomized controlled experiment.
SETTING: Laboratory of Cerebral Microcirculation, Taishan Medical College.
MATERIALS: Sixty involved male adult Kunming mice were provided by the Experimental Animal Center of Shandong University. TNF-α primary antibody, kits for enzyme-linked immunosorbent assay(ELISA) and streptavidin-biotin complex immunohistochemical dyeing kit were purchased from Boster Company(Wuhan). MPO kit was purchased from Jiancheng Bioengineering Institute (Nanjing). Cold light source was developed by Hengfa Co.,Ltd.( LG-150, Xuzhou).
METHODS: This experiment was carried out in the Laboratory of Cerebral Microcirculation of Taishan Medical College between July 2004 and July 2005. The involved 60 Kunming mice were randomized into 3 groups: normal control group (n =6), sham-operation group (n =6) and model group (n =48). Mice in the model group were observed at 30 minutes, 1, 3, 6, 12, 24, 48 and 72 hours after illumination, separately, 6 mice at each time point. In the model group, mice models of local cerebral infarction were developed as follows: The mice were anesthetized to expose left skulls. Taking 2 mm left to sagittal suture and 2 mm posterior to coronal suture as center, a field with diameter of 3 mm for illumination was set. The optical fiber detecting head of cold light source was vertically close to exposed skull. The mice were injected with rose Bengal for 5 minutes, and then cold light source was open for 10 minutes. Illumination was omitted in the sham-operation group. Mice in the control group were not modeled. At postoperative 6 hours, TNF-α expression in infracted-side cortex was detected with immunohistochemical method and ELISA, and MPO activity in infracted-side cortex with chromatometry. MPO activity could reflect the infiltration degree of neutrophils in tissue. Stronger activity indicated severer infiltration. Single-factor analysis of variance was used for comparison among groups, q test for pairwise comparison and correlative analysis for detecting the inter-parameter correlation.
MAIN OUTCOME MEASURES: Changes in TNF-α expression and MPO activity of left cortex of mice in each group.
RESULTS: Sixty mice were involved in the final analysis. After cerebral infarction, TNF-α positive cells were neurons and glial cells mainly, distributing in and around the infarct region. TNF-α expression in cortex of mice of sham-operation group was (615.7±16.1) ng/L, and that of model group increased to (792.2±17.8) ng/L at 3 hours after illumination, and reached peak [(921.9±23.9) ng/L] at 6 hours after illumination, and decreased to (848.0±30.6) ng/L at 12 hours after illumination and recovered to the normal level [(625.3±14.3) ng/L] at 72 hours after illumination. MPO activity of sham-operation group was (7.151±0.433) nkat/g, and that of model group increased to (10.469±0.600) nkat/g at 3 hours after illumination, reached the peak [(15.486±0.650) nkat/g] at 12 hours after illumination, decreased to (11.052±0.617) nkat/g at 24 hours after illumination and recovered to the normal level [(7.418±0.617) nkat/g] at 72 hours after illumination. Change of MPO activity lagged behind that of TNF-α, and correlative analysis showed that the both were positively correlated(r =0.953, P < 0.01).
CONCLUSION: In the acute stage of cerebral infarction of mice induced by photochemical method, TNF-α expression in infarcted-side cortex is closely related with infiltration of neutrophils. TNF-α induces inflammatory cells to intrude into ischemic brain tissue, and participates in the inflammatory reaction process at the early stage of cerebral ischemia. 相似文献
17.
The dynamics of HIF-1α expression during the development of stress-related depression, as well as after hypoxic preconditioning (HP), which has an antidepressant-like effect, were studied in the hippocampus, paraventricular hypothalamic nucleus, and neocortex of rats, using an immunocytochemical method. It has been found that the factor HIF-1α is induced in neurons in response to psychoemotional stress that causes the development of experimental depression in rats in the “learned helplessness” model. The profile of the stress-induced expression of HIF-1α in the hippocampus has a two-wave character: early expression on the first day and the delayed expression 10 days after the stress. No significant change was found in the neocortex. In the hypothalamus, up-regulation of HIF-1α expression was delayed (5–10 days). After HP by a moderate repetitive hypobaric hypoxia, which prevents the development of the depressive state in rats, the post-stress expression of HIF-1α was considerably altered in the brain regions studied. In the hippocampus of HP rats, the peak of the early expression lasted for about 5 days after the stress; we observed a multifold increase in its amplitude. In contrast, the HIF-1α delayed peak was eliminated. A similar but smaller effect of HP was also observed in the hypothalamus. The data obtained indicate that delayed HIF-1α expression in the hippocampus and hypothalamus was apparently involved in the mechanisms of pathogenesis of the depressive pathology. However, strong modifications in early and late post-stress expression of HIF-1α caused by HP obviously play an important role in increasing the brain’s tolerance to severe stresses and protection against the development of stress-induced depressive pathologies. 相似文献
18.
The basis of the pathogenesis of Parkinson’s disease (PD) is progressive degeneration of dopaminergic neurons in the nigrostriatal system of the brain. The most important treatment of PD is using of drugs that delay neuronal death. The aim of the present study was to adapt our model of the early clinical stage of PD in mice [1] for its use as a test system for trials of potential neuroprotectors. Our data show that degeneration of the bodies of dopaminergic neurons in the substantia nigra starts 3 h after the last injection of 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) whereas the number of dopaminergic axons in the striatum is significantly decreased by this time point. Degradation of axons and neuronal bodies continues for the next 3 h. This period of time appears to be more appropriate for testing of neuroprotectors because later the number of neuronal bodies in the substantia nigra and axons in the striatum do not change. For the development of the test system, it is important to evaluate the functional state of surviving neurons. We found that 3 h after the last MPTP injection, the dopamine (DA) content in the substantia nigra decreased to 25% of the control level and 24 h later the DA content increased again and was 70% of the control value. The tyrosine hydroxylase content in neuronal bodies was similar to the control during the entire period of the study. In the striatum, the DA level decreased to 90% 3 h after the last MPTP injection and remained unchanged by the end of the study; however, the content of tyrosine hydroxylase decreased gradually by 12 h after the injection. Our data probably show the compensatory activation of tyrosine hydroxylase in both the substantia nigra and striatum. Thus, in a mouse model of the early clinical stage of PD we revealed that degeneration of nigrostriatal dopaminergic neurons ends 14 h after the start of the action of the specific neurotoxin. This was accompanied by activation of compensatory processes, which enhance DA-ergic neurotransmission. 相似文献
19.
Tokuhara D Yokoi T Nakajima R Hattori H Matsuoka O Yamano T 《Acta neuropathologica》2005,110(4):411-416
Although estrogens possess neuroprotective and epileptogenic properties, the expression pattern of the estrogen receptor (ER) following status epilepticus (SE) remains unclear. We therefore examined the expression pattern of ER in the adult rat hippocampus after SE. SE was induced in rats by kainic acid (KA; 12 mg/kg, i.p.). ER expression was assessed by immunostaining and Western blotting at various times (24 h, and 7, 14, and 21 days) after SE onset. Immunohistochemistry disclosed ER expression in the CA1 and CA3 pyramidal cells of control rats, whereas, after SE, ER-immunoreactive neurons decreased in number due to neuronal death in the CA1 from days 7 to 21. On the other hand, ER-immunoreactive cells with astrocytic morphology were observed in the CA1 beginning on day 7 after SE. This immunoreactivity increased in proportion to the hypertrophy of astrocytes up to day 21. Western blotting revealed a significant decrease in ER expression on day 7 after SE in comparison with control level. However, ER expression on days 14 and 21 were similar when comparing KA-treated and control rats. These results indicate that reactive astrocytes are important sites of estrogen action in the hippocampal CA1 after SE. 相似文献
20.
Parkinson’s disease (PD) is a chronic neurodegenerative disease with a long period of asymptomatic progress, which occurs due to activation of mechanisms of neuroplasticity that support the degenerating nigrostriatal system of the brain. In the present study, we examined some compensatory mechanisms in the mouse brain for the first time using chronic models of preclinical and early clinical stages of PD that we developed. Using a model of the preclinical stage of PD, we found a compensatory increase in the number of monoenzymatic tyrosine hydroxylase-containing fibers in the striatum, whereas using a model of the early clinical stage of PD, an adaptive decrease in the rate of dopamine reuptake in the substantia nigra was revealed. These mechanisms of neuroplasticity may be considered as targets for the future development of new tools for neuroprotective therapy. 相似文献