ABSTRACT
OBJECTIVE: Cephalic Index (CI), the ratio of head width to length, is one of the indexes reflecting cranial morphological characteristics. Current norms were established by European and American countries. The purpose of the study was to study anthropometry of cranial parameters using computed tomography scans to establish the CI of the sampled Chinese Children. METHODS: The cross-sectional study was carried out on patients of age younger than 14 years old at Shanghai Children's Medical Center. The measurement of maximum cranial breadth and maximum cranial length were taken on a computed tomography scan machine and recorded for analysis. Cephalic Index was calculated for each age and sex group and compared with previously established norms. RESULTS: Five hundred eighteen patients met the inclusion criteria, including 301 males and 217 females. The means for boys and girls were 87.1 (SD: 4.3) and 85.8 (SD: 4.3), respectively. There was a significant difference between boys and girls (P < 0.01). Cephalic Index in different ages and on applying the 1-way analysis of variance association was statistically insignificant (P = 0.19). CONCLUSIONS: Chinese head shape was brachycephalic. A statistically significant correlation was seen between the CI and sex, while not age.
ABSTRACT
A chemical investigation on the roots of Aconitum episcopale afforded three undescribed aconitine-type C19-diterpenoid alkaloids, episcopalines A-C (1-3). The structures of the new compounds were elucidated by spectroscopic analysis (NMR, IR, UV, and MS). The isolated alkaloids were tested in vivo for their antinociceptive properties. As a result, episcopaline B (2) showed potent antinociceptive effect and its ID50 value (55.0 µmol/kg) was 2-fold less than those of the positive control drugs aspirin and acetaminophen.
Subject(s)
Aconitum , Alkaloids , Diterpenes , Aconitum/chemistry , Alkaloids/chemistry , Analgesics/pharmacology , Diterpenes/chemistry , Diterpenes/pharmacology , Molecular Structure , Plant Roots/chemistryABSTRACT
Four iridoids (1-4), five iridoid glucosides (5-9), and three triterpenoids (10-12) were isolated from the ethyl acetate soluble fraction of 70% Me2CO extract of the aerial parts of Viburnum ternatum through various column chromatographies over silica gel, ODS, Sephadex LH-20 and MCI. Their structures were elucidated as ternatumin A (1), 2,9-dioxatricyclo[4.3.1.03ï¼7]decanes (2), 7,10,2'-triacetylsuspensolide F (3), 7,10,2',3'-tetraacetylsuspensolide F (4), viburtinoside IV (5), viburtinoside II (6), viburtinoside B (7), luzonoside A (8), luzonoside B (9), 2α,3ß,24-trihydroxy-12-ursen-28-oic acid (10), 6-hydroxy-20(29)-lupen-3-one (11), and pomalic acid (12) based on the their chromatographic properties, chemical and physicochemical methods, and spectroscopic data. Compound 1 was a new compound and compounds 3-12 were isolated from this plant for the first time. Furthermore, we note here the first isolation of compound 2 as a new natural product.
Subject(s)
Iridoids/isolation & purification , Terpenes/isolation & purification , Viburnum/chemistry , Chromatography , Molecular Structure , Plant Components, Aerial/chemistryABSTRACT
OBJECTIVE: The activity of eicosanoid pathways is critical to the inflammatory and immune responses that are associated with the progression of atherosclerosis. Yet, the signals that regulate these pathways are poorly understood. Here, we address whether the innate immune signals of nucleotide-binding oligomerization domain-containing protein (NOD) 2 affect eicosanoids metabolism in atherosclerosis. APPROACH AND RESULTS: Analysis of human carotid plaques revealed that NOD2 was abundantly expressed at both mRNA and protein levels by endothelial cells and macrophages. Stimulation of NOD2 in ex vivo-cultured carotid plaques by muramyl dipeptide, an extrinsic ligand of NOD2, led to release of prostaglandin E2, upregulation of cyclooxygenase-2 and microsomal prostaglandin E synthase-1, and to downregulation of cyclooxygenase-1. NOD2 was coexpressed with cyclooxygenase-2 in lesional macrophages. NOD2-induced cyclooxygenase-2 expression in macrophages was dependent on p38 mitogen-activated protein kinase activation and was mediated by interleukin-1ß and tumor necrosis factor-α. Selective lipidomic analysis of the eicosanoids released by the carotid plaques characterized the metabolites of 12-, 5-, and 15-lipoxygenase as the predominant eicosanoids that were produced by the atherosclerotic lesion in the absence of additional stimuli. Unlike the prostaglandin E2 pathway, metabolic activity of the lipoxygenase pathways was not altered on the short-term activation of NOD2 in carotid plaques. CONCLUSIONS: These results suggest that atherosclerosis may involve enhanced NOD2-mediated innate immunity. Activation of NOD2 preferentially upregulates the prostaglandin E2 pathway. Nevertheless, lipoxygenase pathways, such as 12-lipoxygenase, predominate the basal synthesis and metabolism of eicosanoids in atherosclerotic plaques. These findings provide new insights into the regulation of eicosanoids in atherosclerosis.
Subject(s)
Carotid Arteries/metabolism , Carotid Artery Diseases/metabolism , Eicosanoids/metabolism , Immunity, Innate , Nod2 Signaling Adaptor Protein/metabolism , Signal Transduction , Acetylmuramyl-Alanyl-Isoglutamine/metabolism , Arachidonate 12-Lipoxygenase/metabolism , Arachidonate 15-Lipoxygenase/metabolism , Arachidonate 5-Lipoxygenase/metabolism , Carotid Arteries/immunology , Carotid Arteries/pathology , Carotid Artery Diseases/genetics , Carotid Artery Diseases/immunology , Carotid Artery Diseases/pathology , Case-Control Studies , Cells, Cultured , Cyclooxygenase 2/metabolism , Dinoprostone/metabolism , Endothelial Cells/immunology , Endothelial Cells/metabolism , Fibroblasts/immunology , Fibroblasts/metabolism , Humans , Interleukin-1beta/metabolism , Ligands , Nod2 Signaling Adaptor Protein/genetics , Plaque, Atherosclerotic , Time Factors , Tissue Culture Techniques , Transcription, Genetic , Transcriptional Activation , Tumor Necrosis Factor-alpha/metabolism , Up-Regulation , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Acute coronary syndrome (ACS) is one of the leading causes of death in cardiovascular disease. Percutaneous coronary intervention (PCI) is an important method for the treatment of coronary heart disease (CHD), and it has greatly reduced the mortality of ACS patients since its application. However, a series of new problems may occur after PCI, such as in-stent restenosis, no-reflow phenomenon, in-stent neoatherosclerosis, late stent thrombosis, myocardial ischemia-reperfusion injury, and malignant ventricular arrhythmias, which result in the occurrence of major adverse cardiac events (MACE) that seriously reduce the postoperative benefit for patients. The inflammatory response is a key mechanism of MACE after PCI. Therefore, examining effective anti-inflammatory therapies after PCI in patients with ACS is a current research focus to reduce the incidence of MACE. The pharmacological mechanism and clinical efficacy of routine Western medicine treatment for the anti-inflammatory treatment of CHD have been verified. Many Chinese medicine (CM) preparations have been widely used in the treatment of CHD. Basic and clinical studies showed that effectiveness of the combination of CM and Western medicine treatments in reducing incidence of MACE after PCI was better than Western medicine treatment alone. The current paper reviewed the potential mechanism of the inflammatory response and occurrence of MACE after PCI in patients with ACS and the research progress of combined Chinese and Western medicine treatments in reducing incidence of MACE. The results provide a theoretical basis for further research and clinical treatment.
Subject(s)
Acute Coronary Syndrome , Coronary Disease , Percutaneous Coronary Intervention , Humans , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/methods , Acute Coronary Syndrome/drug therapy , Treatment Outcome , Stents/adverse effectsABSTRACT
The aim of this study is to investigate the effect and mechanism of angiotensin (Ang) II on E-selectin and vascular cell adhesion molecule-1 (VCAM-1) expression in rat brain microvascular endothelial cells (BMEC) and evaluate the effect of compound EXP-2528, a novel Ang II type 1 (AT1) receptor antagonist. The experiment was performed in cultured BMEC of rat. The mRNA and protein expression of E-selectin and VCAM-1 in BMEC was analyzed by RT-PCR and Western blotting, respectively. The results showed that the mRNA and protein expression of E-selectin and VCAM-1 in BMEC were significantly upregulated by 4 h or 18 h exposure to 1 x 10(-7) mol x L(-1) Ang II. These effects were abolished by pretreatment with the selective AT1 receptor antagonists losartan and compound EXP-2528, but not with the AT2 selective antagonist PD123319. Combining losartan with PD123319 also significantly inhibited Ang II-induced E-selectin and VCAM-1 expression in BMEC, but there was no significant difference compared with losartan group. These findings indicated that Ang II upregulated E-selectin and VCAM-1 in BMEC by activating AT1 receptor and then involved in the development of cerebrovascular disease.
Subject(s)
Angiotensin II Type 1 Receptor Blockers/pharmacology , E-Selectin/metabolism , Endothelial Cells/metabolism , Imidazoles/pharmacology , Isoxazoles/pharmacology , Vascular Cell Adhesion Molecule-1/metabolism , Angiotensin II/pharmacology , Animals , Brain/blood supply , Cells, Cultured , E-Selectin/genetics , Losartan/pharmacology , Microvessels/cytology , RNA, Messenger/metabolism , Rats , Vascular Cell Adhesion Molecule-1/geneticsABSTRACT
Microvascular changes in the brain are significant causes of cerebral edema and ischemia injury. A number of studies suggest that angiotensin (Ang) II may be involved in the initiation and regulation of processes occurring in brain ischemia. We recently reported that Ang II injures brain microvascular endothelial cells (BMEC) partially via stimulating intercellular adhesion molecule-1 (ICAM-1) expression. However, the signaling cascade leading to Ang II-induced ICAM-1 expression in BMEC was unclear. The present study tested the hypothesis that Ang II induces ICAM-1 expression via an AT1 receptor/nuclear factor-kappaB (NF-kappaB) pathway in BMEC. Ang II directly stimulated the expression of ICAM-1 mRNA and protein in primary cultured BMEC. Ang II treatment also resulted in the degradation of IkappaBalpha and increase of NF-kappaB p65 subunit in the nucleus as well as the DNA binding activity of nuclear NF-kappaB. These effects were abolished by pretreatment with the selective AT1 receptor antagonists, losartan and compound EXP-2528, or losartan plus the AT2 receptor antagonist PD123319, but not by PD123319 alone. Moreover, there were no significant differences between the losartan and losartan plus PD123319 groups. These findings indicate that Ang II-induced ICAM-1 upregulation in brain microvascular endothelial cells may be mediated via an AT1 receptor/NF-kappaB pathway.
Subject(s)
Angiotensin II/pharmacology , Cerebrovascular Circulation , Endothelium, Vascular/physiology , Intercellular Adhesion Molecule-1/physiology , Microcirculation/physiology , NF-kappa B/physiology , Receptor, Angiotensin, Type 1/physiology , Animals , Endothelium, Vascular/drug effects , Gene Expression Regulation/drug effects , Intercellular Adhesion Molecule-1/drug effects , Intercellular Adhesion Molecule-1/genetics , RNA, Messenger/genetics , Rats , Rats, Wistar , Receptor, Angiotensin, Type 1/drug effectsABSTRACT
AIM: To study the protective effects of hydroxyethylpuerarin against the injury of astrocytes induced by hydrogen peroxide (H2O2). METHODS: Experiments were performed with cells from passage 4. Plasma membrane integrity was measured by lactate dehydrogenase (LDH) release. The occurrence of apoptosis was measured by flow cytometry. The glutamate uptake of astrocytes was studied with [3H]-glutamate incorporation. Intracellular superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were assessed by automatic biochemistry analyzer. RESULTS: Compared with H2O2 injured group, the occurrence of apoptosis, levels of LDH release and intracellular MDA of astrocytes reduced in hydroxyethylpuerarin pre-treated groups, but the glutamate uptake and intracellular SOD activity of astrocytes increased. CONCLUSION: Hydroxyethylpuerarin could reduce the occurrence of apoptosis and improve neurotrophic function of astrocytes, which may be related with its antioxidant effects during oxidative stress.
Subject(s)
Apoptosis/drug effects , Astrocytes/metabolism , Isoflavones/pharmacology , Neuroprotective Agents/pharmacology , Pueraria , Animals , Animals, Newborn , Antioxidants/isolation & purification , Antioxidants/pharmacology , Astrocytes/cytology , Astrocytes/drug effects , Brain/cytology , Brain/metabolism , Cells, Cultured , Glutamic Acid/metabolism , Hydrogen Peroxide/toxicity , Isoflavones/isolation & purification , L-Lactate Dehydrogenase/metabolism , Malondialdehyde/metabolism , Neuroprotective Agents/isolation & purification , Plants, Medicinal/chemistry , Pueraria/chemistry , Rats , Rats, Wistar , Superoxide Dismutase/metabolismABSTRACT
AIM: To observe the damages induced by hydrogen peroxide in cultured bovine cerebral microvascular endothelial cells (BCMEC) and evaluate the protective effects of hydroxyethylpuerarin on hydrogen peroxide-injured BCMEC. METHODS: BCMEC were cultured and transferred into modified Eagle medium (MEM). The viability of cells was detected by MTT assay. Cell injury was determined by lactate dehydrogenase (LDH) activity in the extracellular medium. Flow cytometry was employed to observe the occurrence of apoptosis. Morphologic changes of cells were visualized under phase contrast and electron microscopes. RESULTS: Hydrogen peroxide (200 micromol x L(-1) for 4 hours) inhibited the viability of cultured BCMEC and stimulated LDH release. Hydrogen peroxide (100 micromol x L(-1) for 4 hours) induced the occurrence of apoptosis. Hydroxyethylpuerarin was shown to increase the survival rate and decrease the activity of LDH of BCMEC damaged by hydrogen peroxide. Hydroxyethylpuerarin was also found to protect BCMEC against apoptosis induced by hydrogen peroxide. CONCLUSION: Hydrogen peroxide induces BCMEC injury either by apoptosis or through necrosis. Hydroxyethylpuerarin protects BCMEC against hydrogen peroxide-induced injury in a concentration-dependent manner. Its antioxidant effects might be involved as the mechanism protection.
Subject(s)
Antioxidants/pharmacology , Apoptosis/drug effects , Drugs, Chinese Herbal/pharmacology , Endothelial Cells/metabolism , Isoflavones/pharmacology , Neuroprotective Agents/pharmacology , Animals , Antioxidants/administration & dosage , Antioxidants/isolation & purification , Brain/blood supply , Cattle , Cell Survival/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/isolation & purification , Endothelial Cells/drug effects , Hydrogen Peroxide/toxicity , Isoflavones/administration & dosage , Isoflavones/isolation & purification , Microcirculation/drug effects , Microcirculation/metabolism , Neuroprotective Agents/administration & dosage , Neuroprotective Agents/isolation & purification , Plant Roots/chemistry , Plants, Medicinal/chemistry , Pueraria/chemistryABSTRACT
Pharmacologically blocking or stimulating studies have showed the crucial role of adenosine receptors in the protective effect of cerebral ischemic preconditioning (CIP). However, little is know about whether the adenosine receptors are up-regulated in the process. In the present study, changes in expression of adenosine receptors in the CA1 hippocampus after a short CIP in a period of 3 min were investigated in rat four-vessel occluding (4VO) brain ischemic model using immunohistochemistry. The experiments were performed on groups of sham, 4 h, 1, 3, and 7 days (n = 6 in each group) after the CIP. The number and immunostaining density of immunoreactive cells for A1 and A2b adenosine receptors in the CA1 hippocampus were significantly increased after the CIP. For A1 adenosine receptor, the increase occurred in CA1 pyramidal neurons. While for A2b adenosine receptor, the increase occurred in the stratum radiatum of the CA1. The immunoreactive cells for A2b receptor showed distinct morphological characteristics of astrocytes. The increases were consistent in time course (1-7 days) with the development of the ischemic tolerance induced by the CIP. It was concluded that up-regulation of adenosine receptors may also play an important role in the protective effect of CIP.
Subject(s)
Brain Ischemia/metabolism , Hippocampus/blood supply , Receptors, Purinergic P1/metabolism , Animals , Astrocytes/metabolism , Hippocampus/metabolism , Immunohistochemistry , Ischemic Preconditioning , Rats , Rats, Sprague-Dawley , Time Factors , Up-RegulationABSTRACT
Sixteen serratane-type triterpenoids including three new compounds, 14beta,15beta-epoxyserratan-3beta,21beta,29-triol (1), serrat-14-en-3beta,21beta,29-triol (2) and serrat-14-en-3alpha,21beta,24,29-tetraol (3), were isolated from the whole plant of Huperzia serrata (Thunb) Trev. The structures of these new compounds (1-3) were elucidated on the basis of spectral analysis.
Subject(s)
Huperzia , Phytotherapy , Triterpenes/chemistry , Humans , Magnetic Resonance Spectroscopy , Plant Components, Aerial , Plant RootsABSTRACT
The purpose of this study was to investigate the effects of limb ischemic preconditioning (LIP) on apoptosis of pyramidal neurons in the CA1 hippocampus induced by global cerebral ischemia-reperfusion in rats. Forty-six rats whose bilateral vertebral arteries were occluded permanently were assigned to one of four groups: sham group, limb ischemia group, cerebral ischemia group and LIP group. LIP was performed by occluding the bilateral femoral arteries for 10 min 3 times in an interval of 10 min. Global cerebral ischemia was underwent by occluding the bilateral common carotid arteries for 8 min immediately after LIP. Assays for apoptosis of the hippocampal neurons were biologically and morphologically performed using gel electrophoresis, TUNEL and AO/EB staining. Characteristic DNA ladder was clearly visualized with gel electrophoresis in the hippocampus in cerebral ischemia group, but not in LIP group. The number of TUNEL-positive cells in the CA1 hippocampus was significantly reduced by LIP from 69.8+/-12 (cerebral ischemia group) to 17.8+/-5.8 (P<0.01). AO/EB staining also showed a reduction of apoptosis in LIP group compared with cerebral ischemia group. These results suggest that LIP can inhibit hippocampal neuronal apoptosis induced by cerebral ischemia-reperfusion, which contributes to the protection against the delayed neuronal death induced by cerebral ischemic insult.
Subject(s)
Brain Ischemia/physiopathology , Hippocampus/pathology , Ischemic Preconditioning , Lower Extremity/blood supply , Reperfusion Injury/prevention & control , Animals , Apoptosis/physiology , Ischemic Preconditioning/methods , Male , Neurons/pathology , Pyramidal Cells/pathology , Rats , Rats, WistarABSTRACT
To explore the role of metabotropic glutamate receptor 2/3 mGluR 2/3 in the induction of brain ischemic tolerance (BIT), the influences of mGluR2/3 antagonist alpha-methyl-(4-tetrazolyl-phenyl) glycine (MTPG) on the induction of BIT and expression of glial fibrillary acidic protein (GFAP) in the hippocampus were observed using thionin staining and GFAP immunohistochemical staining in a rat brain ischemic model with four-vessel occlusion (4VO). Fifty-four rats, of which bilateral vertebral arteries were occluded permanently by electrocautery, were divided into 5 groups: (1) sham operated group (n=8): the bilateral carotid common arteries (BCCA) were separated, but the blood flow was not blocked; (2) ischemia group (n=8): the blood flow of BCCA was blocked for 8 min; (3) ischemic preconditioning (IP) group (n=8): the blood flow of BCCA was occluded for 3 min as a cerebral ischemic preconditioning (CIP), and then the rats were exposed to an 8-min brain ischemic insult 24 h after the CIP; (4) MTPG+IP group (n=22): MTPG was administered 20 min before the CIP, then the rats were exposed to an 8-min brain ischemia insult 24 h after the CIP. In order to examine dosage dependency in the effect of MTPG, 4 dosages of MTPG (0.4, 0.2, 0.04 and 0.008 mg) were administered; (5) MTPG+ischemia group (n=8): an ischemic insult for 8 min was given 24 h after the administration of MTPG (0.2 mg). MTPG was injected into the right lateral cerebral ventricle. The results obtained are as follows. (1) Ischemic insult for 8 min increased the histological grade (HG) and reduced the neuronal density (ND) significantly, and also increased the expression of GFAP significantly (P<0.05 vs sham-operated group). (2) In the IP group, the above changes were not observed, indicating that CIP could protect pyramidal neurons against the ischemic insult. (3) The protective effects of CIP were blocked by MTPG, as manifested by the significant increase in HG and decrease in ND in the MTPG+IP group (P<0.05 vs sham-operated group). The changes were dose-dependent. (4) No obvious difference in the HG, ND and expression of GFAP was detected between the groups of MTPG+ischemia and ischemia. The above results indicate that MTPG blocks the induction of BIT induced by CIP, suggesting that mGluR2/3 participates in the induction of BIT.
Subject(s)
Alanine/analogs & derivatives , Hippocampus/blood supply , Ischemic Preconditioning/methods , Receptors, Metabotropic Glutamate/antagonists & inhibitors , Reperfusion Injury/prevention & control , Tetrazoles/pharmacology , Alanine/pharmacology , Animals , Brain Ischemia/physiopathology , Hippocampus/drug effects , Hippocampus/physiopathology , Male , Rats , Rats, Sprague-Dawley , Reperfusion Injury/physiopathologyABSTRACT
To explore the role of NO in the induction of brain ischemic tolerance (BIT) in vivo, the effect of nitric oxide synthase (NOS) inhibitor L-NAME on the induction of BIT induced by cerebral ischemic preconditioning (CIP) was investigated in the hippocampal CA1 subfield in CIP and ischemic insult models established by rat four-vessel occlusion using brain tissue section and thionine staining methods. Fifty-four male Wistar rats were divided into 6 groups: (1) sham-operated group (n=6): bilateral common arteries were separated without occluding the cerebral blood flow; (2) ischemia group (n=6): an ischemic insult for 10 min was given; (3) CIP+ischemia group (n=6): 3-min CIP was preformed 72 h prior to 10-min ischemic insult; (4) L-NAME group (total n=24, n=6 for each subgroup): L-NAME (5 mg/kg, i.p.) was administered 1 h prior to CIP and 1, 12 and 36 h after CIP, respectively. Other procedures were the same as those for the CIP+ischemia group; (5) L-NAME+L-Arg group (n=6): L-NAME (5 mg/kg, i.p.) and L-Arg (300 mg/kg, i.p.) were administered 1 h prior to CIP, other procedures were the same as those for the L-NAME group; (6) L-NAME+ischemia group (n=6): L-NAME (5 mg/kg, i.p.) was administered 72 h before the 10-min ischemic insult. The results showed that (1)10-min ischemic insult resulted in an increase in the histological grade (indicating a more serious tissue injury) and a decrease in pyramidal neuronal density (P<0.01); (2) the histological grade and neuronal density in hippocampal CA1 in the CIP+ischemia group were similar to those in the sham-operated group (P>0.05); (3) in the L-NAME group, administration of L-NAME brought about an increase in the histological grade and a decrease in neuronal density (P<0.01), suggesting that L-NAME blocked the protection of CIP; (4) the neuronal damage in L-NAME+L-Arg group was slighter than that in the L-NAME group, but still more serious than that in the CIP+ischemia group, suggesting that L-Arg partly reversed the blocking effect of L-NAME; (5) the morphological representations in L-NAME+ischemia group were basically similar to those in the ischemia group. The results mentioned above indicate that NO is involved in the induction of BIT in vivo. The blocking effect of L-NAME administered at 36 h after CIP was obviously weaker than the effects of L-NAME administered 1 h prior to CIP, and 1 or 12 h after CIP. It is suggested that NO is involved in the induction of BIT at an early stage and that the involvement might take place via activating cascades of the events.
Subject(s)
Brain Ischemia/physiopathology , Ischemic Preconditioning/methods , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide/physiology , Animals , Brain Ischemia/prevention & control , Enzyme Inhibitors/pharmacology , Hippocampus/physiology , Male , Rats , Rats, WistarABSTRACT
AIM: To explore the role of nitric oxide (NO) resulted from nNOS in the mGluR2/3 mediated-brain ischemic tolerance induced by cerebral ischemic preconditioning (CIP), the present study is undertaken to observe the influences of alpha-methyl-(4-tetrazolyl-phenyl) glycine (MTPG), an antagonist of mGluR2/3, on the expression of nNOS during the induction of the brain ischemic tolerance based on confirming the blocking effect of MTPG on the induction of the tolerance. METHODS: Thirty-six Sprague-Dawley rats, whose vertebral arteries were permanently occluded, were randomly divided into sham, CIP, ischemic insult, CIP+ ischemic insult, MTPG+ CIP and MTPG+ CIP+ ischemic insult groups. Thionin staining and immunohistochemistry were used for neuropathological evaluation and assay of nNOS expression in the hippocampal CA1 subregion of the rats. RESULTS: The expression of nNOS showed moderate and extreme up-regulation in the CIP and ischemia groups, respectively, compared to the sham group. The preceded CIP blocked in certain extent the extreme up-regulation of nNOS induced by brain ischemia in CIP + ischemia group. Administration of MTPG via lateral cerebral ventricle 20 min before CIP blocked the up-regulation of nNOS induced by CIP, but had no influence on the pyramidal neuronal survival. While in the MTPG+ CIP+ ischemic insult group, the expression of nNOS was stronger than that in the MTPG + CIP group, and the up-regulation was accompanied with obvious delayed neuronal death. Discussion concerned illustrated that the relative intensive up-regulation of nNOS in this group might be attributed to brain ischemia other than MTPG. CONCLUSION: NO resulted from nNOS participated the induction of mGluR2/3 mediated-brain ischemic tolerance as a downstream molecule of activation of mGluR2/3 during CIP.
Subject(s)
Ischemic Preconditioning/methods , Nitric Oxide Synthase Type I/metabolism , Nitric Oxide/physiology , Receptors, Metabotropic Glutamate/physiology , Alanine/analogs & derivatives , Alanine/pharmacology , Animals , Brain Ischemia/metabolism , Brain Ischemia/physiopathology , Male , Random Allocation , Rats , Rats, Sprague-Dawley , Receptors, Metabotropic Glutamate/antagonists & inhibitors , Tetrazoles/pharmacologyABSTRACT
This paper, taking the Mengjia River gully area of Junzilan Park in Changchun City of Jilin Province as an example, studied the longitudinal differentiation regularity of heavy metals in topsoil covered with different vegetation in gully area. The soil samples were collected from the gully slope, 2 m away from the gully bank, covered with arbor, shrub, vegetable and barren land along longitudinal profile in parallel with the flow direction, which was used to analyze the contents of Zn, Pb and Cu in the topsoil. The results indicate that the contents of these heavy metals have obvious difference. The content of Zn ranges from 70.3 mg x kg(-1) to 290.9 mg x kg(-1), the content of Pb from 39.8 mg x kg(-1) to 79.3 mg x kg(-1), and the content of Cu from 20.3 mg x kg(-1) to 63.4 mg x kg(-1). They all follow the declined order: barren, vegetable, arbor, and shrub. Moreover, the contents of these heavy metals were higher than their soil background values respectively. Thus, it can be assumed that they have accumulation tendency.
Subject(s)
Metals, Heavy/analysis , Plant Development , Soil Pollutants/analysis , Vegetables/growth & development , China , Copper/analysis , Lead/analysis , Zinc/analysisABSTRACT
AIM: To investigate the effects of the duration of cerebral ischemic preconditioning(CIP) and interval between CIP and the subsequent ischemic insult on the protection of CIP against delayed neuronal death (DND) in the CA1 hippocampus normally induced by brain ischemic insult. METHODS: Four-vessel occlusion cerebral ischemic model of rats (54) was used. The brain of the rats was sectioned and stained with thionin to show DND in the CA1 hippocampus. RESULTS: No DND was found in the hippocampus of the rats subjected to sham operation and CIP, in which 3 min cerebral ischemic preconditioning was performed. Obvious destruction of the CA1 hippocampus was found in brain ischemic insult group, in which histological (HG) was 2-3 in 6 min and 10 min ischemia subgroups and grade 3 in 15 min ischemia subgroup. In CIP + brain ischemic insult group, no obvious neuronal damage was found in 3 min-3d-6 min (CIP for 3 min was followed by a brain ischemic insult for 6 min at an interval of 3 d, the same as the following) and 3 min-3 d-10 min groups, indicating that CIP effectively protected neurons of the CA1 hippocampus against DND normally induced by ischemic insult for 6 or 10 min. However, in 3 min-1 d-10 min and 3 min-3 d-15 min groups, the protective effect of CIP was lower than that in the 3 min-3 d-10 min group. The quantitative analysis of the protective effect of CIP on the CA1 hippocampal neurons showed that there was no significant difference in protecting number and protecting index between 3 min-3 d-6 min and 3 min-3 d-10 min groups (P > 0.05). However, the growth index in 3 min-3 d-10 min group was obvious larger than that in 3 min-3 d-6 min (P < 0.05). CONCLUSION: Although the protective effects of CIP in 3 min-3 d-6 min and 3 min-3 d-10 min groups were similar, the protective effect of CIP in 3 min-3 d-10 min group was sensitively found. Maximal protective potential of CIP could be induced when using the time parameters of 3 min-3 d-10 min to establish the model of global cerebral ischemic tolerance.
Subject(s)
Brain Ischemia/prevention & control , Hippocampus/pathology , Ischemic Preconditioning , Neurons/pathology , Animals , Brain Injuries/pathology , Brain Injuries/prevention & control , Brain Ischemia/pathology , Cell Death , Male , Rats , Rats, Wistar , Time FactorsABSTRACT
The present study was undertaken to observe in vivo changes of expression and phosphorylation of ERK1/2 proteins during brain ischemic preconditioning and effects of inhibiting generation of nitric oxide (NO) on the changes to determine the role of ERKs in the involvement of NO participating in the acquired tolerance. Fifty-five Wistar rats were used. Brain ischemic preconditioning was performed with four-vessel occlusion for 3 min. Total ERK1/2 proteins and phospho-ERK1/2 in the CA1 hippocampus were assayed with Western immunoblot. Total ERK1/2 proteins did not change in period from 5 min to 5 days of reperfusion after preconditioning stimulus. While the level of phospho-ERK1/2 increased obviously to 223, 237, 300, 385 and 254% of sham level at times of 5 min, 2 h, 1, 3 and 5 days after preconditioning stimulus, respectively (P < 0.01). Administration of L-NAME, an inhibitor of NO synthase, 30 min prior to preconditioning stimulus failed to induce change in total ERK1/2 proteins (P > 0.05). However, phospho-ERK1/2 increased only to 138 and 176% of sham level at 2 h and 3 days after preconditioning stimulus, respectively, when animals were pretreated with L-NAME. The magnitudes of the increase were obviously low compared with those (237 and 385%) in animals untreated with L-NAME at corresponding time points (P < 0.01), which indicated that phosphorylation of ERK1/2 normally induced by preconditioning stimulus was blocked apparently by administration of L-NAME. The results suggested that phosphorylation of ERK1/2, rather than synthesis of ERK1/2 proteins, was promoted in brain ischemic preconditioning, and that the promotion was partly mediated by NO signal pathway.
Subject(s)
Adaptation, Physiological , Brain Ischemia/physiopathology , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Nitric Oxide/physiology , Signal Transduction , Animals , Apoptosis , Male , Rats , Rats, WistarABSTRACT
AIM: To explore roles of metabotropic glutamate receptor1/5 (mGluR1/5) in the induction of brain ischemic tolerance (BIT) induced by cerebral ischemic preconditioning (CIP), influences of mGluR1/5 ligand (s)-4-carboxy-3-hydroxy- phenylglycine ((s)-4C3HPG) on the induction of BIT and expression of glial fibrillary acidic protein (GFAP) in the hippocampus were observed. METHODS: Thionin staining and GFAP immunohistochemistry staining in rat 4 vessel occlusion (4VO) brain ischemic model was used. Thirty-six rats, of which bilateral vertebral arteries were occluded permanently by electrocautery, were divided into the following 4 groups: sham group; ischemic insult group, BIT group and (s)-4C3HPG group. According to dosages of (s)-4C3HPG used, the (s)-4C3HPG group, was further divided into 0.2 mg, 0.04 mg and 0.008 mg subgroups. All the rats were killed 7 d after the operation or the final ischemic treatment. RESULTS: (1) The ischemic insult for 8 min increased the histological grade (HG), decreased the pyramidal neuronal density (ND) and increased the expression of GFAP significantly (P < 0.05 vs sham) (2) The CIP prevented the above injury changes in the BIT group. (3) The protective effects of the CIP were blocked by (s)-4C3HFG, as manifested by significant increases in HG and decreases in ND in the (s)-4C3HPG group (P < 0.05 vs sham and BIT groups). The changes were proportional with the dosages of (s)-4C3HPG used. CONCLUSION: (s)-4C3HPG could block the induction of BIT induced by CIP, suggested that mGluR1/5 participate in the induction of BIT.
Subject(s)
Brain Ischemia/metabolism , Glial Fibrillary Acidic Protein/metabolism , Neuroglia/metabolism , Receptors, Metabotropic Glutamate , Animals , Brain Ischemia/physiopathology , Electroencephalography , Glycine/analogs & derivatives , Glycine/pharmacology , Ischemic Preconditioning , Male , Rats , Rats, Sprague-Dawley , Receptor, Metabotropic Glutamate 5 , Receptors, Metabotropic Glutamate/antagonists & inhibitors , Receptors, Metabotropic Glutamate/metabolismABSTRACT
AIM: To explore the effects of limb ischemic preconditioning (LIP) on cerebral ischemia/reperfusion injuries. METHODS: Thirty six wistar rats, of which bilateral vertebral arteries were occluded permanently, were randomly divided into the following 6 groups: control group, cerebral ischemic group, limb ischemic group, LIP 0 d group (cerebral ischemia was given immediately after LIP), LIP 1 d group (cerebral ischemia was given 1 d after LIP) and LIP 2 d group (cerebral ischemia was given 2 d after LIP). Global cerebral ischemia was performed by four vessels occlusion in rats. LIP was performed by occluding the bilateral femoral arteries for 10 min 3 times in a interval of 10 min. The histological grade and pyramidal neuronal density in the CA1 hippocampus were measured to quantitate the degree of hippocampal injury under thionin staining. RESULTS: The histological grade was increased and the pyramidal neuronal density was decreased in the CA1 hippocampus of the cerebral ischemic group (P < 0.01). The damage of the CA1 hippocampus in LIP 0 d group was significantly diminished, which represented by decreased histological grade and increased neuronal density compared with the cerebral ischemic group (P < 0.01). But the CA1 hippocampus still showed obvious injuries in the LIP 1 d and LIP 2 d group. CONCLUSION: LIP performed immediately prior to cerebral ischemia could confer obvious protective effects on CA1 hippocampus against cerebral ischemia/reperfusion injuries. But LIP performed 1 d and 2 d prior to cerebral ischemia could not afford the protection against injuries induced by cerebral ischemia/reperfusion.