dl-3n-Butylphthalide promotes angiogenesis via the extracellular signal-regulated kinase 1/2 and phosphatidylinositol 3-kinase/Akt-endothelial nitric oxide synthase signaling pathways.

We have previously demonstrated that dl-3n-butylphthalide (NBP) has a potential angiogenic activity. In this study, we investigated the angiogenic effect of NBP and the molecular mechanisms underlying NBP-mediated angiogenesis. Zebrafish embryos and human umbilical vein endothelial cells were treated with various doses of NBP and several signaling pathway inhibitors. NBP induced ectopic subintestinal vessel production in zebrafish embryos and induced invasion, migration, and endothelial cell tube formation of human umbilical vein endothelial cells in a dose-dependent manner. These NBP-induced angiogenic effects were partially suppressed by SU5402, a fibroblast growth factor receptor 1 inhibitor; U0126, an extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor; LY294002, a phosphatidylinositol 3-kinase inhibitor; 1L6-hydroxymethyl-chiro-inositol-2-(R)-2-O-methyl-3-O-octadecyl-sn-glycerocarbonate, an Akt inhibitor; cavtratin, an endothelial nitric oxide synthase (eNOS) inhibitor and completely inhibited by a combination of U0126 and LY294002. NBP enhanced phosphorylation of ERK1/2 and fibroblast growth factor receptor 2 expression, which were inhibited by U0126. NBP increased the phosphorylation of Akt and eNOS at serine 1177, which was blocked by LY294002. NBP-stimulated nitric oxide production, which was reduced by LY294002. Our data demonstrated that (1) NBP promoted angiogenesis and (2) the angiogenic effects of NBP were mediated by the ERK1/2 and phosphatidylinositol 3-kinase/Akt-eNOS signaling pathways. Our findings suggest that NBP could be a novel agent for therapeutic angiogenesis in ischemic diseases.

A retrospective review of 15 patients with familial myasthenia gravis over a period of 25 years.

We observed, during a 25-year period, 15 patients from 6 families with autoimmune myasthenia gravis (all Chinese Han from Guangdong Province) referred to our department. Their mean onset age was 13.4 years (range 2-25 years) with 10 patients with juvenile onset. The female:male ratio was 3:2. Acetylcholine receptors antibody titers were increased in 11 patients (range 1.62-19.8 nmol/L). Thymectomy was performed in six patients, who received corticosteroids /immune inhibitor plus pyridostigmine treatments after surgery. The other patients were placed on therapy with azathioprine, cyclophosphamide, corticosteroids and acetylcholinesterase inhibitors. All patients responded well to immunosuppressants, and psychiatric symptoms were observed only in one patient who received a high dose of corticosteroids. Patients with generalized type in the same family had different presentations with variable prognosis. HLA-A 0207 was found in 9 patients (9/15), HLA-B 4601 in 11 patients (11/15), and HLA-DRB1 0901 in 12 patients (12/15). When compared to familial autoimmune myasthenia gravis in other countries, we observed peculiar characteristics of Chinese populations, such as the within-family consistency was only found in families with ocular MG type (50% of all MG families), while the pathogenetic conditions and the prognoses of the generalized MG patients may differ greatly within the same family. These findings may shed new light on the genetic predisposition and the origin of immune abnormalities of MG patients.

Marine cyclotripeptide X-13 promotes angiogenesis in zebrafish and human endothelial cells via PI3K/Akt/eNOS signaling pathways.

Cyclotripeptide X-13 is a core of novel marine compound xyloallenoide A isolated from mangrove fungus Xylaria sp. (no. 2508). We found that X-13 dose-dependently induced angiogenesis in zebrafish embryos and in human endothelial cells, which was accompanied by increased phosphorylation of eNOS and Akt and NO release. Inhibition of PI3K/Akt/eNOS by LY294002 or L-NAME suppressed X-13-induced angiogenesis. The present work demonstrates that X-13 promotes angiogenesis via PI3K/Akt/eNOS pathways.

[Response to thymectomy and analysis of influencing factors in the treatment of children with myasthenia gravis].

OBJECTIVE: To evaluate the efficacy of thymectomy and relevant influencing factors in the treatment of children with myasthenia gravis through a long-term follow-up. METHODS: The clinical records of 59 patients undergoing expanded thymectomy for the treatment of myasthenia gravis (MG) between January 2003 and August 2009 were reviewed retrospectively. Their postoperative outcomes were categorized into complete stable remission (CSR), pharmacological remission (PR), improvement, no change and deterioration (including mortality). RESULTS: During a median follow-up period of 35 months, none of them died or deteriorated clinically among 53 patients with a postoperative follow-up. The overall remission rate was 69.8% and the effective rate 90.6%. No symptomatic relapse occurred among 16 patients in CSR. None of the ocular patients progressed to generalized MG while 16 thymectomized generalized MG developed from ocular MG. Both univariate and logistic regression analyses revealed that the preoperative duration of illness influenced the surgical curative effect (P < 0.05). Survival analysis indicated that the rates of overall remission were 56% or 88% at 24 months and 42% or 75% at 48 months among ocular MG and generalized MG respectively. According to Log-rank analysis, no difference in remission existed between two types of MG. CONCLUSION: Thymectomy is an effective and safe treatment in selected MG children, especially in those with a shorter illness duration.

[Therapeutic efficacy and safety of tacrolimus for intractable myasthenia gravis: a report of 36 patients].

OBJECTIVE: To examine the efficacies and adverse events of low-dose tacrolimus in intractable myasthenia gravis (MG) patients during a long-term follow-up. METHODS: Tacrolimus was administered at 0.1 mg×kg(-1)×d(-1) to 36 generalized or ocular MG patients at our department from November 2008 to December 2010. The efficacies of tacrolimus were assessed by the myasthenia gravis activities of daily living (MG-ADL) profile and the classification of Myasthenia Gravis Foundation of America (MGFA). And the adverse events of tacrolimus were monitored in each patient. RESULTS: (1) All patients were followed up for 7 - 23 months. Adverse events occurred in 6 patients (16.67%). (2) The myasthenic symptoms improved up to the levels of MG-ADL and MGFA in 24 patients (66.67%). There was notable statistical significance in the comparison of clinical status at pre- and post-treatment (P = 0.000). (3) The efficacies in patients with generalized MG were better than those with ocular MG (P = 0.032). (4) The average blood trough levels of tacrolimus were lower than the recommended maintenance range from other countries in 24 effective patients. CONCLUSION: The administration of tacrolimus induces symptomatic improvements in MG patients especially in generalized type. And the adverse events should be closely monitored.

[Roles of Bacillus Calmette-Guérin with immunological memory in the pathogenesis of myasthenia gravis].

OBJECTIVE: To explore the roles of immunological memory in the pathogenesis of myasthenia gravis (MG) by Bacillus Calmette-Guérin (BCG). METHODS: For this randomized comparative clinical trial, 58 newly diagnosed MG patients and 32 age-and-gender-matched healthy controls were analyzed by purified protein derivative (PPD) test. The results were observed after 72 hours. peripheral blood mononuclear cell (PBMC) was collected from the MG patients before and after extended thymectomy and cultured with BCG. After a 72-hour incubation, the level of interferon gamma (IFN-γ) was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: In PPD test, the MG patients did not show a markedly higher positive percentage [48.3% (28/58) vs 65.6% (21/32), P = 0.114]. The pre-thymectomy PBMC had a higher level of IFN-γ than the control group: (650 ± 312) pg/ml vs (346 ± 153) pg/ml. After extended thymectomy, the level of IFN-γ returned to normal: (219 ± 113) pg/ml. The P value is 0.003, 0.001. CONCLUSION: The impairment of immunological memory, may be an important pathogenic cause of relapse in the MG patients.

[Correlation study between Chinese myasthenia gravis patients from Guangdong province and the polymorphism of HLA immunogene].

OBJECTIVE: To explore the correlation between Chinese myasthenia gravis (MG) patients from Guangdong province and the polymorphism of HLA immunogene. METHODS: The genotypes of HLA-A, B and DRB1 alleles in 104 MG patients and 121 healthy blood donors were detected by PCR-SBT (polymerase chain reaction-sequencing-based typing). RESULTS: (1) There were 15 alleles at A locus, 32 at B locus and 23 at DRB1 locus in MG group. (2) The frequency of HLA-A*02:07(P = 0.000, RR = 3.715), -B*46:01(P = 0.000, RR = 5.698), -DRB1*04:03(P = 0.033, RR = 6.312), -DRB1*09:01(P = 0.000, RR = 5.884) in MG patients was higher than that in healthy controls. (3) There were positive associations of HLA-DRB1*09:01(P = 0.000, RR = 1.349) with juvenile-onset ocular MG. CONCLUSION: There is susceptibility association of HLA-A*02:07, -B*46:01, -DRB1*04:03, -DRB1*09:01 with Chinese MG patients from Guangdong province. There is a close genetic and immunological correlation between HLA alleles and the pathogenesis of MG. It has directional significance in the race and region incidence study, clinical classification, differential diagnosis, treatment and prognosis of MG.

Relationship between cerebral hypoxic tissue volume and prognosis after stroke.

BACKGROUND/AIMS: Between 50 and 70% of stroke survivors suffer from severe disabilities such as paralysis and aphasia. Poor stroke outcome is a reflection of our incomplete understanding of the underlying mechanisms, and hence the capacity to implement appropriate treatment(s). We evaluated hypoxic tissue after stroke and patient condition severity and prognosis. METHODS: Hypoxic tissue volume was quantified within 14 days after stroke. Patients were classified as hypoxic positive or negative. Patients were evaluated at imaging and 21 days later. Prognosis was assessed at 30 and 90 days. RESULTS: Significant improvement was shown in hypoxia-positive (vs. hypoxia-negative) patients (p < 0.05). There were significant positive relationships between the volume of hypoxic tissue and the improvement in specialized test scores at 90 days (p < 0.05 for both). Presence of hypoxic tissue within 14 days after cerebral stroke was related to recovery at 3 weeks and prognosis at 90 days. CONCLUSIONS: The assessment of hypoxic tissue volume after stroke may be useful in predicting patient recovery.

[Analysis of prognostic factors and efficacy of plasmapheresis in the treatment of myasthenia crisis].

OBJECTIVE: To examine the prognostic factors and efficacy of myasthenia gravis (MG) in crisis on plasmapheresis and detect the reasons for ineffective plasmapheresis. METHODS: The investigators analyzed a total of 69 MG patients in crisis on plasmapheresis by case control study. Gender, age at onset of myasthenic symptoms, duration between the onset of crisis and plasmapheresis, pre-therapeutic use of glucocorticoids, pulmonary infections, other complications, nutritional status, history of thymectomy in 48 hours before crisis, thymic pathology, combined intravenous immunoglobulin (IVIG) and total sessions of plasmapheresis were measured retrospectively. RESULTS: Univariate analysis showed that pulmonary infections (P = 0.000, OR = 29.250), history of thymectomy in 48 hours before crisis (P = 0.046, OR = 0.267), combined intravenous immunoglobulin (P = 0.003, OR = 0.136) and total sessions of plasmapheresis (P = 0.022, OR = 0.498) were all influencing factors of plasmapheresis. However the analysis of multivariate logistic regression revealed that pulmonary infections (P = 0.000, OR = 23.600) was an independent risk factor and combined intravenous immunoglobulin (P = 0.047, OR = 0.192) was an independent protection factor of plasmapheresis. CONCLUSION: Plasmapheresis is ineffective in MG crisis with pulmonary infections. Control of pulmonary infections and combined intravenous immunoglobulin can improve the response to plasmapheresis in patients with MG crisis.

[Mediation of cellular immune response by TP5 in pathogenesis of myasthenia gravis].

OBJECTIVE: To evaluate the effects of TP5 upon the production of IFN-gamma and different T cell subsets by human peripheral blood mononuclear cells (PBMCs) from patients with myasthenia gravis (MG) and to provide experimental rationales for TP5 in clinical therapy of MG. METHODS: PBMCs were isolated from peripheral blood of MG individuals and cultured with anti-CD3. The level of IFN-gamma in culture supernatants was examined by ELISA. The subsets and frequency of IFN-gamma-producing cells were examined at a single-cell level by flow cytometry. RESULTS: After PBMCs stimulation with anti-CD3 and TP5 (300 microg/ml), the level of IFN-gamma expression was significantly inhibited (P(child) = 0.0001, P(adult) = 0.01); and the level of IFN-gamma expression from normal adult and child controls was also significantly inhibited (P(child) = 0.009, P(adult) = 0.0001). In addition, the inhibition of TP5 on the production of IFN-gamma by PBMCs from MG children was lower compared with normal child control. But as compared with normal adult control, the inhibition of TP5 showed no significant difference in MG adults (P(adult) = 0.481). TP5 inhibited the expression of IFN-gamma by CD8+ T cell and CD4+ T cell. CONCLUSION: TP5 can inhibit the response of cellular immune by decreasing the production of IFN-gamma in MG consequence display that the level of IFN-gamma significant decreased with the addition of TP5 and anti-CD3. But after considering the age, the level of IFN-gamma in MG children was no as much inhibited as normal child. TP5 inhibits the expression of IFN-gamma by CD8+ T and CD4+ T cells.

[Expression of regulatory T cells in thymus of myasthenia gravis patients].

OBJECTIVE: To investigate the in situ expression of regulatory T cells (Tregs) in thymus and its significance for myasthenia gravis (MG). METHODS: Thirty nine MG patients who had not accepted immunosuppressive therapy before thymectomy were recruited as study group and 19 patients undergoing cardiosurgery as control. There was no significant statistical difference in age and gender between the two groups (P > 0.05). The location and proportion of Tregs in thymus were analyzed using indirect immunofluorescence double labeling immunohistochemistry and image analysis software. RESULTS: (1) Tregs were all located in medulla zone of thymus in control and MG groups. (2) Cells of germinal center had a high expression of CD25 and a low expression of CD4. It indicates that a majority of germinal center cells were B cells. (3) There were fewer Tregs around germinal center. (4) There was no statistical significant difference in absolute number of Tregs between the two groups (P > 0.05). But the proportion of Tregs was higher in control group (P < 0.05). CONCLUSION: The proportion of thymus Tregs decreases in MG so as to weaken the function of immuno-regulation and suppression. This is probably a precipitating factor of MG.

[Thymopentin 5 in treatment of relapse after extended thymectomy: a randomized comparative clinical trial of 135 patients with myasthenia gravis].

OBJECTIVE: To investigate the effect of thymopentin 5 (TP5) combined with immunosuppressive agents in treatment of relapse after extended thymectomy in patients with myasthenia gravis (MG). METHODS: One hundred thirty-five MG patients who were to undergo extended thymectomy, 62 adults and 73 children, were randomly assigned to 2 groups: non-TP5 group (n = 60) treated with intramuscular injection of prednisone + pyridostigmine daily for 3 months as a basic treatment, and TP5 group (n = 73), treated with prednisone + pyridostigmine + TP5 for 3 months. Follow-up was conducted for more than 1 year. RESULTS: The remission rates of children in the TP5 group at different time points were all markedly higher than those in the non-TP5 group, and the remission rates of children in the TP5 group during the period of 2 months to 2 years after thymectomy were all significantly higher (all P < 0.05). And the remission rates of the adults of the TP5 group during the period of 6 months to 2 years after thymectomy were all significantly higher than those of the non-TP5 group (all P < 0.05). In the pediatric cases the withdrawal rate of the TP5 group was significantly higher, and the relapse rate was significantly lower than those of the non-TP5 group. No side effect developed during the follow-up. CONCLUSION: TP5 is effective in reducing relapse and has a higher drug withdrawal rate, especially among children.

Dysphonia as a primary manifestation in myasthenia gravis (MG): a retrospective review of 7 cases among 1520 MG patients.

Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission, usually recognized with ocular complaints or generalized muscle weakness. However, among the 1520 MG cases that had been diagnosed and treated in our hospital in the last 15 years (1990-2005), we have identified 7 MG patients whose initial and prominent complaint was dysphonia and all had been misdiagnosed elsewhere. The diagnoses were confirmed with fibrolaryngoscope and voice analysis employed before and after a positive neostigmine (anticholinesterase) test. Electromyography with repetitive stimulations, single-fiber electromyography, and laboratory and radiographic evaluations were also conducted for diagnosis. A surprisingly low seropositivity rate of anti-acetylcholine-receptor antibodies (1/7) and anti-MuSK (Muscle Specific Kinase) antibodies (0/6) were found in these dysphonia MG patients. A cholinesterase inhibitor (ChEI) and immunosuppressive therapy were applied for treatment. Extended thymectomy was applied to MG patients with thymus hyperplasia or thymic tumor. Significant improvement was found in all 7 cases after these treatments. We have developed a sere of diagnostic protocol for this rare type of laryngeal MG, and discussed the clinical implication of our data. In summary, dysphonia or laryngeal disorder can be the only prominent manifestation of MG in rare cases, which should be taken into consideration during the diagnosis to patients with exclusive laryngeal complaints.

dl-3n-butylphthalide prevents stroke via improvement of cerebral microvessels in RHRSP.

The purpose of the study is to establish a model of cold-induced stroke in hypertensive rats, and to study the preventive effect of dl-3n-butylphthalide ( NBP ) on stroke. Stroke-prone renovascular hypertension(RHRSP) was created in Sprague-Dawley rats. The animals were assigned randomly to NBP, aspirin treated and vehicle control group, with administration of the medications for 7 days, and then subjected to cold treatment in an environmentally controlled chamber for 3 days to induce the occurrence of stroke. The incidence of stroke, the volume of the brain lesion, patency of the microvessels by FITC-dextran perfusion and the number of microvessels by immunohisochemical detection of vwF were investigated. Cold induced different types of stroke in RHRSP. The incidence of ischemic stroke and the volume of the infarct were decreased, and the perfused microvessels were increased with NBP pretreatment. Our data suggest that NBP prevents cold-induced ischemic stroke via improvement of cerebral microvessels.

[Prognostic factors of myasthenic crisis after extended thymectomy in patients with generalized myasthenia gravis].

OBJECTIVE: To investigate the prognostic factors of myasthenic crisis after extended thymectomy in patients with generalized myasthenia gravis (MG). METHODS: Extended thymectomy was performed on 176 patients with generalized MG, 74 males and 102 females, aged 4 - 67, of which 36 experienced postoperative myasthenic crisis and required prolonged mechanical ventilation. The relations among the age, sex, preoperative course of disease, pathologic type of thymus, Osserman classification, history of infection during 1 month preoperatively, history of myasthenic crisis 1 month preoperatively, thymoma, preoperative daily dose of pyridostigmine, preoperative steroid use, operation time, intra-operative blood loss, and intra-operative pleura injury and postoperative myasthenia crisis were analyzed. RESULTS: Univariate analysis showed that bulbar symptoms (OR = 8.494, P = 0.001), history of myasthenic crisis 1 month preoperatively (OR = 5.667, P = 0.000), thymoma (OR = 2.147, P = 0.047), Osserman types III and IV (OR = 0.459, P = 0.000), history of infection during 1 month preoperatively (OR = 3.30, P = 0.038), large pre-operative dose of pyridostigmine (OR = 1.019, P = 0.001), long operation time (OR = 1.012, P = 0.034), and more blood loss (186 ml +/- 163 ml) (OR = 1.004, P = 0.012), were all prognostic factors or postoperative myasthenic crisis. However, multivariate logistic regression analysis revealed that preoperative bulbar symptoms (OR = 7.709, P = 0.003), history of infection during 1 month preoperatively (OR = 4.582, P = 0.037), history of myasthenic crisis 1 month preoperatively (OR = 4.526, P = 0.001, large pre-operative dose of pyridostigmine (OR = 1.016, P = 0.001) were prognostic factors of postoperative myasthenic crisis. CONCLUSION: Preoperative bulbar symptoms, history of preoperative myasthenic crisis, history of preoperative infection, and large preoperative dose of, pyridostigmine are all independent influencing factors of postoperative myasthenic crisis. Ample preoperative care may prevent postoperative myasthenic crisis in the patients with such factors.

[Long-term efficacy of enlarged thymectomy in treatment of myasthenia gravis and relevant influencing factors: study of 410 cases].

OBJECTIVE: To investigate the long-term efficacy of enlarged thymectomy in treatment of myasthenia gravis (MG) and relevant influencing factors. METHODS: 546 patients with MG underwent enlarged thymectomy and were followed up for 28 months (6 to 85 months). Effective follow-up data were obtained from 410 out of the 546 patients. The clinical data of these 410 patients, 199 males and 211 females, were analyzed. RESULTS: The remission rate was 42.9% and the effective rate was 82.3%. Multivariate logistic regression analysis revealed that short duration of preoperative period was an independent factor of the surgical curative effect (odds ratio = 0.310, P = 0.006) and sex, age, Osserman classification, pathologic type of thymus seemed to be irrelevant to the surgical curative effect. CONCLUSION: Thymectomy is an effective measure for MG and shows a better prognosis in the patients with shorter illness duration.

[Clinical value of the immune parameters in patients with myasthenia gravis].

OBJECTIVE: To evaluate the clinical value of the indices, including IgG, IgA, IgM, CD3, CD4 and CD8. METHODS: Detect CD3, CD4, CD8 by flow cytometry and detect IgG, IgA, IgM by turbidimetric method. We analyzed clinical features according to different classification of immune index, and changes of the level of these immune indices before and after treatment. RESULT: The level of IgG, IgA in patients with generalized MG was higher than that of ocular MG (P < 0.05). The ratio of CD4 to CD8 was classified into 3 groups: low (118 cases), high (60 cases), normal (68 cases). Likewise, the level of IgG, IgA, IgM was classified into 4 groups: low (156 cases), high (65 cases), disorder (31 cases), normal (67 cases). There was no statistically significance on changes of level of these immune indices before and after treatment. There was no statistically significance on clinical materials among different groups. In the low group of humoral immunity, the remission ratio of the patients with the treatment of gamma globulin was higher than that of patients without gamma globulin (95.2%, 28.8%, respectively. P < 0.01). CONCLUSION: The immune indices of IgG, IgA, IgM, CD3, CD4, CD8 seemed to be irrelevant to severity of disease and prognosis. To some extent, these immune indices can be reference in the aspect of treatment.

Cultured human embryonic neocortical cells survive and grow in infarcted cavities of adult rat brains and interconnect with host brain.

BACKGROUND: There are no reports on exnografting cultured human fetal neocortical cells in this infracted cavities of adult rat brains. This study was undertaken to observe whether cultured human cortical neurons and astrocytes can survive and grow in the infarcted cavities of adult rat brains and whether they interconnect with host brains. METHODS: The right middle cerebral artery was ligated distal to the striatal branches in 16 adult stroke-prone renovascular hypertensive rats. One week later, cultured cells from human embryonic cerebral cortexes were stereotaxically transferred to the infarcted cavity of 11 rats. The other 5 rats receiving sham transplants served as controls. For immunosuppression, all transplanted rats received intraperitoneal injection of cyclosporine A daily starting on the day of grafting. Immunohistochemistry for glial fibrillary acidic protein (GFAP), synaptophysin, neurofilament, and microtubule associated protein-2 (MAP-2) was performed on brain sections perfused in situ 8 weeks after transplantation. RESULTS: Grafts in the infarcted cavities of 6 of 10 surviving rats consisted of bands of neurons with an immature appearance, bundles of fibers, and GFAP-immunopositive astrocytes, which were unevenly distributed. The grafts were rich in synaptophysin, neurofilament, and MAP2-positive neurons with long processes. The graft/host border was diffuse with dendrites apparently bridging over to the host brain, into which neurofilament immunopositive fibers protruded. CONCLUSION: Cultured human fetal brain cells can survive and grow in the infarcted cavities of immunodepressed rats and integrate with the host brain.

[A study on shifts of cerebral autoregualtion following end-tidal CO2 by critical closing pressure].

OBJECTIVE: To investigate the shifts of cerebral autoregulation following end-tidal CO2, and set up a new clinical way to evaluate the lower limit of cerebral autoregulation. METHODS: The cerebral blood flow spectrum of middle cerebral artery, radial blood pressure and end-tidal CO2 (ETco(2)) were simultaneously monitored among 70 healthy volunteers, 38 males and 41 females, aged 21-77. The Lower limit of cerebral autoregulation (LLCA) was determined by critical closing pressure (CCP). We observed the shifts of LLCA of healthy subjects respectively between normocapnia and hyper- and hypocapnia. RESULTS: The LLCA of healthy subjects was 58 mm Hg +/- 10 mm Hg at normocapnia, increased at hypercapnia and decreased at hypocapnia significantly (69 mm Hg +/- 15 mm Hg and 44 mm Hg +/- 11 mm Hg, P < 0.05). The 95% CI of difference were 2.70 mmHg between hyper- and normocapnia and 2.18 mm Hg between hypo- and normocapnia. The shifting rates of LLCA correlated inversely to the rates of CCP at both hyper- and hypocapnia (r = -0.610 5, -0.555 1, both P < 0.05), and the relation between LLCA's and CCP's shifts displayed an "S" pattern curve at hypocapnia. The rate of mean velocity changing in middle cerebral artery was significantly correlative to the LLCA shifts' rate (r = 0.584 1, P < 0.05), and showing an "S" pattern curve. CONCLUSION: The lower limit of cerebral autoregulation can be determined by CCP exactly. The cerebral autoregulation can shift up or down following ETco(2), and its physiological basis is closely correlated with the cerebrovascular tone.

[EphB2-Fc promotes activation of endogenous neural stem cells after cerebral cortex infarction: experimental with hypertensive rats].

OBJECTIVE: To explore the effects of intraventricular injection of EphB2-Fc on activation of inherent neural stem cells after cerebral cortex infarction. METHODS: Stroke-prone renovascular hypertension model was established in 96 SD rats by two-kidney, two-clip method. Middle cerebral artery occlusion (MCAO) model was established in 72 of these 96 stroke-prone renovascular hypertensive rats and the other 24 rats were used as sham operation group. Then the 72 rats were randomly divided into 3 equal groups: cerebral infarction group without any treatment after the MCAO, MCAO + EphB2-Fc group undergoing stereotaxical infusion of EphB2-Fc at the dose of 20 microl x 200 microg/ml into the lateral ventricle 4 days after the distal ligation of right middle cerebral artery, and MCAO + IgG-Fc group undergoing stereotaxical infusion of IgG-Fc at the dose of 20 microl x 200 microg/ml into the lateral ventricle 4 days after the distal ligation of right middle cerebral artery. By the ends of the first and fourth weeks after the MCAO procedure 12 rats from each group were killed and their brains were taken out to undergo in situ hybridization, immunohistochemistry and Western blotting analysis in order to determine the expression of EphB2 protein and mRNA, nestin and polysialic acid-neural cell adhesion molecule (PSA-NCAM). RESULTS: One week after the distal ligation of right middle cerebral artery, the EphB2 protein and mRNA expression levels in the ipsilateral cortex and subventricular zone (SVZ) of the cerebral infraction group were both lower than those of the sham operation group (P < 0.05), such levels of the MCAO + EphB2-Fc group were higher than those of the MCAO + IgG-Fc group (both P < 0.05), but there was no significant difference between the cerebral infraction group and IgG-Fc group (both P > 0.05), and there were no differences in such levels between the cerebral infarction group and MCAO + IgG-Fc group (both P > 0.05); the nestin and PSA-NCAM expression levels in the ipsilateral SVZ of the cerebral infraction group were both higher than those of the sham operation group (both P < 0.05), such levels of the MCAO + EphB2-Fc group were both higher than those of the MCAO + IgG-Fc group (both P < 0.05), and migration of PSA-NCAM positive cells to corpus callosum could be seen. Four weeks after, there were no significant differences in the expression levels of EphB2 protein and mRNA among different groups (all P > 0.05), the nestin and PSA-NCAM expression levels in the ipsilateral SVZ decreased in all groups, there were no significant differences in the expression of nestin among all groups, but the PSA-NCAM expression in the ipsilateral SVZ of the cerebral infraction group was still higher than that of the sham operation group. CONCLUSION: Disruption of EphB2 signal promotes the proliferation and migration of endogenous neural stem cells in the SVZ after cerebral cortex infarction.