Effectiveness of Surgical Treatments for Basal Ganglia Hemorrhage and Imaging Factors Affecting Hematoma Evacuation Rate by Neuroendoscopic Surgery.

BACKGROUND: Basal ganglia hemorrhage (BGH) is a devastating neurologic disease with high morbidity and mortality, and its management is still controversial. We evaluated the effectiveness of surgical treatments for BGH and investigated computed tomography (CT) imaging features affecting the hematoma evacuation rate (ER) in patients treated with neuroendoscopic surgery. MATERIALS AND METHODS: A total of 104 BGH patients who underwent craniotomy, burr-hole drainage, or neuroendoscopic surgery were analyzed retrospectively. Clinical characteristics, imaging features, and postoperative complications were compared. Univariate and multivariate regression analyses were applied to identify imaging factors associated with ER. RESULTS: A significant difference in ER was observed: 78.4% in patients treated with neuroendoscopic surgery, 33.6% in patients treated with burr-hole drainage, and 82.5% in patients treated with craniotomy (p < 0.001). Similar results were observed for operative time (p < 0.001). Five cases (12.5%) of rebleeding were found in patients treated with burr-hole drainage (p = 0.020). No significant difference was found for pneumonia, intracranial infection, gastrointestinal bleeding, hospital mortality, hospital stay, expenses, 3-day Glasgow Coma Scale (GCS) scores after surgery, or GCS at discharge. The CT imaging feature, the island sign (p = 0.004), was observed as an independent factor correlated with lower ER for neuroendoscopic surgery. CONCLUSIONS: The benefits and drawbacks of surgical treatments confirmed they have their own indications, and neuroendoscopic surgery may be relatively beneficial for BGH treatment. The island sign was an independent factor affecting ER for neuroendoscopic surgery. Therefore, comprehensive assessment of clinical data, especially the island sign, should be performed preoperatively in BGH patients.

Effect of Chaihu-Shugan-San on the mRNA expression of the 5-HT1A receptor and cellular proliferation in the hippocampus of epileptic rats with depression.

Chaihu-Shugan-San (CHSGS) is a herbal preparation that has been shown to effectively relieve neurologic impairment and reduce depression. However, the efficacy of CHSGS in the treatment of patients with epilepsy with depression is unknown. Therefore, in the present study, adult rats were exposed to chronic mild stress following the establishment of chronic pilocarpine-induced epilepsy. Subsequently, a sucrose consumption test and open-field test (OFT) were performed to assess depression-like behavior. Rats were randomly divided into four groups: Control, model, fluoxetine (1.8 g/kg) and CHSGS (2.7 g/kg) groups. The control and model groups received normal saline. The mRNA expression levels of the 5-hydroxytryptamine 1A (5-HT1A) receptor and the number of 5-bromo-2'-deoxyuridine (BrdU)-labeled cells in the hippocampal dentate gyrus were detected using reverse transcription-quantitative polymerase chain reaction and immunohistochemical analysis, respectively. Treatment administration was conducted by once daily intragastric perfusion for 28 days. The mRNA expression levels of the 5-HT1A receptor, the number of BrdU-labeled cells in the hippocampal dentate gyrus, the consumption of sucrose, and frequency of vertical and horizontal movement scores in the OFT were enhanced in the fluoxetine and CHSGS groups compared with the model group (P<0.05). However, no statistically significant difference was detected between the fluoxetine and CHSGS groups. These data suggest that CHSGS is able to increase the expression of 5-HT1A receptor mRNA and cellular proliferation in the hippocampal dentate gyrus in epileptic rats with depression, and thus effectively improve certain symptoms of depression.

[Effect of the chelator BPCBG on the decorporation of uranium in vivo and uranium-induced damage of human renal tubular epithelial cells in vitro].

This study is to assess the efficacy of BPCBG on the decorporation of uranium (VI) and protecting human renal proximal tubular epithelial cells (HK-2) against uranium-induced damage. BPCBG at different doses was injected intramuscularly to male SD rats immediately after a single intraperitoneal injection of UO2(CH3COO)2. Twenty-four hours later uranium contents in urine, kidneys and femurs were measured by ICP-MS. After HK-2 cells were exposed to UO2(CH3COO)2 immediately or for 24 h followed by BPCBG treatment at different doses for another 24 or 48 h, the uranium contents in HK-2 cells were measured by ICP-MS, the cell survival was assayed by cell counting kit-8 assay, formation of micronuclei was determined by the cytokinesis-block (CB) micronucleus assay and the production of intracellular reactive oxygen species (ROS) was detected by 2',7'-dichlorofluorescin diacetate (DCFH-DA) oxidation. DTPA-CaNa3 was used as control. It was found that BPCBG at dosages of 60, 120, and 600 micromol kg(-1) resulted in 37%-61% increase in 24 h-urinary uranium excretion, and significantly decreased the amount of uranium retention in kidney and bone to 41%-31% and 86%-42% of uranium-treated group, respectively. After HK-2 cells that had been pre-treated with UO2(CH3COO)2 for 24 h were treated with the chelators for another 24 h, 55%-60% of the intracellular uranium was removed by 10-250 micromol L(-1) of BPCBG. Treatment of uranium-treated HK-2 cells with BPCBG significantly enhanced the cell survival, decreased the formation of micronuclei and inhibited the production of intracellular ROS. Although DTPA-CaNa3 markedly reduced the uranium retention in kidney of rats and HK-2 cells, its efficacy of uranium removal from body was significantly lower than that of BPCBG and it could not protect uranium-induced cell damage. It can be concluded that BPCBG effectively decorporated the uranium from UO2(CH3COO)2-treated rats and HK-2 cells, which was better than DTPA-CaNa3. It could also scavenge the uranium-induced intracellular ROS and protect against the uranium-induced cell damage. BPCBG is worth further investigation.

Effect of bone marrow stromal cell-conditioned medium on the glutamate uptake of peroxide-injured astrocytes.

We aimed to investigate the effect of bone marrow stromal cell-conditioned medium (BCM) on glutamate uptake of peroxide (H(2)O(2))-injured astrocytes. Bone marrow stromal cells (BMSC) were isolated from rat bone marrow. Confluent BMSC cultures were incubated with serum-free Dulbecco's Modified Eagle's Medium to create the BCM. Astrocytes were isolated from 1-day-old rats. H(2)O(2)-injured astrocytes were cultured in BCM (experimental group) or serum-free medium (control group). The labeled glutamate ((3)H-L-glutamate) uptake by H(2)O(2)-injured astrocytes with or without BCM was compared after 1 and 3 days. We found that astrocytes cultured in BCM exhibited increased glutamate uptake compared to those cultured in serum-free medium following H(2)O(2)-induced injury (p<0.01) and concluded that BCM increased the glutamate uptake capability of H(2)O(2)-injured rat astrocytes. The therapeutic benefits associated with BMSC transplantation following brain injury might be partly due to increased glutamate uptake by astrocytes.

Comparison of add-on valproate and primidone in carbamazepine-unresponsive patients with partial epilepsy.

PURPOSE: Evaluation of the efficacy of add-on valproate (VPA) or primidone (PRM) in patients with partial epilepsy unresponsive to carbamazepine (CBZ). METHODS: The trial was prospective and open. Patients, aged 8-58 years, with partial epilepsy who did not become seizure free on CBZ were randomized to either VPA add-on or PRM add-on. The baseline period and the evaluation period were both 3 months. Proportions of patients with different degrees of reduction in seizure frequency were determined. RESULTS: Significantly more patients on VPA (51% of 68 patients) achieved a greater than 50% seizure reduction than on PRM (34% of 68 patients). There was no significant difference in percentage seizure free (26% and 16%, respectively) or in percentage treatment withdrawals due to adverse effects. CONCLUSION: Our results indicated that the efficacy of the CBZ/VPA combination tends to be greater than the efficacy of the CBZ/PRM combination.

A ditopic colorimetric sensor for fluoride ion based on thiourea mercury complex.

A novel ditopic chromogenic receptor, N-5-(8-hydroxy)quinoline-N'-4'-nitro-phenyl thiourea (1), was synthesized. The metal complex 1-Hg(2+) showed sensitive and highly selective responses to F(-) over other anions such as CH(3)CO(2)(-), H(2)PO(4)(-), HSO(4)(-) and Cl(-). 1-Hg(2+)-F(-) complex formed, which promoted the intramolecular charge transfer and led to a dramatic spectral change. The color of 1-Hg(2+) solution changed from colorless to red upon addition of F(-). Thus, a colorimetric assay of F(-) was developed in acetonitrile by naked-eye detection. F(-) behaved linearly in the 8.0 x 10(-6) to 2.0 x 10(-5) mol L(-1) concentration range with LOD as 1.4 x 10(-6) mol L(-1).

[Effects of cyclin dependent protein kinase inhibitor olomoucine on the neuronal apoptosis after status epilepticus: experiment with rats].

OBJECTIVE: To investigate the effects of olomoucine, a cyclin dependent protein kinase (CDK) inhibitor, on the neuronal apoptosis after status epilepticus (SE). METHODS: Lithium chloride was injected intraperitoneally, and pilocarpine was injected intraperitoneally after 18 h to 24 SD rats so as to cause SE. Twenty-two of the 24 rats developed SE and 2 of them died. The surviving 20 rats were then randomly divided into 2 equal groups: olomoucine group, injected intracerebroventricularly after the SE was terminated by diazepam and chloral hydrate once a day for 3 days, and SE group, infused intracerebroventricularly with DMSO solution Another 10 rats were injected intraperitoneally with normal saline and then infused intracerebroventricularly with DMSO solution to be used as control group. Six hours after SE attack 5 rats from each group were killed respectively with their brains taken out. Semiquantitative RT-PCR was used to detect the mRNA expression of anti-inflammatory cytokines, such as interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. Three days later the other 5 rats in each group were killed with their entorhinal cortex and hippocampus taken out. TUNEL was used to observe the apoptosis. Immunofluorescence (IF) staining was used to detect the expression of neuronal nuclear nucleoprotein (NeuN) and cyclin B1. RESULTS: TUNEL showed that apoptotic neurons were rare in the control group and were numerous in the SE group, especially in the entorhinal cortex and the hylus of dentate gyrus, and the number of apoptotic neurons in the hylus of dentate gyrus of the olomoucine group was not significantly different from that of the control group (P < 0.05), however, the number of apoptotic cells in the entorhinal cortex of the olomoucine group was still significantly higher than that of the control group (P < 0.05). IF staining demonstrated that in the control group the co-expression of NeuN and TUNEL-labeled cells was weak; and in the SE group the co-expression of NeuN and TUNEL was significantly increased compared with that in the control group (P < 0. 05). The number of cyclin B1 positive cells in the olomoucine group was 18.22 +/- 3.99, significantly lower than that of the SE group (24.57 +/- 6.78, P < 0.05). Semiquantitative RT-PCR showed that the IL-1beta and TNF-alpha mRNA expression levels of the SE group were both significantly higher than those of the control group (both P < 0.05), and the IL-1beta and TNF-alpha mRNA expression levels of the olomoucine group, except the TNF-alpha mRNA expression in the cortex, were all significantly lower than those of the SE group (all P < 0.05), and not significantly different from those of the control group (all P > 0.05). CONCLUSION: Olomoucine treatment can inhibits cell cycle protein B1 expression, anti-inflammatory cytokines such as IL-1beta and TNF-alpha secretion, thus decreasing neuronal death and providing neuroprotection after SE, which suggests a potential promising therapeutic way for epilepsy treatment.

[Reversion of multidrug resistance (MDR) in human glioma cells by RNA interference (RNAi)].

OBJECTIVE: To explore whether the constructed vector of short haprin in vivo can induce human glioma cell line BT325 to produce RNAi duplexes and reverse the expression of MDR1 gene. METHODS: Three 62nt oligonucleotide fragments (shRNA) were constructed according to GenBank MDR1 sequence and were cloned to the retrovirus-delivered vectors. After transfected these vectors directly into the human malignant glioma BT325 cells by lipofectamine 2000 with enhanced green fluorescence protein (EGFP) co-transfecting, the MDR1 gene silence effects were detected by the changing level of mRNA and P-glycoprotein including real time PCR (RT-PCR), Northern blot and Western blot analysis. To assess the multidrug resistance against adriamycin (ADR) and VCR, cell proliferation assays were performed by cell counting kit-8. RESULTS: The RNAi plasmid vectors were constructed successfully. RT-PCR showed MDR1 mRNA was significantly reduced (P < 0.05). Northern blot analysis showed that the gene silence became most intense at 48 hours after transfection. Western blot analysis demonstrated that P-gp expression was reduced at different time to 12.9%, 30.3% and 4.8%, respectively. The chemosensitivity assays indicated that the transfected cells showed an enhanced sensitivity to ADR and VCR. Based on the value of IC(50), BT325 cells had significantly increased sensitivity to the drugs. CONCLUSION: The sequence specific RNAi can inhibit MDR1 mRNA and P-gp expression in the glioma cell line. It may reverse multidrug resistance phenotype, therefore, may provide promising therapeutic modalities in the treatment of human glioma.

Treatment with valproate after status epilepticus: effect on neuronal damage, epileptogenesis, and behavioral alterations in rats.

Epileptogenesis, i.e. the process leading to epilepsy with spontaneous recurrent seizures, can be initiated by a number of brain damaging insults, including traumatic brain injury, status epilepticus (SE), and stroke. Such acquired epilepsy is often associated with memory impairment and behavioral problems. There has been a growing interest in the use of antiepileptic drugs (AEDs) for neuroprotection and prevention or modification of epileptogenesis induced by such brain insults. One promising candidate in this respect is valproic acid (VPA), a widely used AED that has been reported to exert neuroprotective activity in a number of in vitro and in vivo models. The present study investigated whether VPA reduces brain damage and improves functional outcome in a rat model of post-SE epilepsy. A self-sustaining SE was induced by prolonged electrical stimulation of the basal amygdala via a depth electrode. SE was terminated after 4 h by diazepam, immediately followed by onset of treatment with VPA. VPA was injected i.p. at a bolus dose of 400 mg/kg, followed by three times daily administration of 200 mg/kg for 4 weeks. A control group received vehicle instead of VPA after SE. Spontaneous seizures were recorded in all rats of both groups following termination of treatment, without significant inter-group difference in seizure frequency or severity. However, treatment with VPA after SE prevented the hyperexcitability and locomotor hyperactivity observed in vehicle-treated epileptic rats. Furthermore, VPA completely counteracted the neuronal damage in the hippocampal formation, including the dentate hilus. The data demonstrate that, although VPA does not prevent the occurrence of spontaneous seizures after SE, it exerts powerful neuroprotective effects and prevents part of the behavioral alterations, demonstrating that administration of VPA immediately after SE exerts a favorable effect on long-term functional outcome.

[Regulatory effect of small interfering RNA targeting multidrug resistant protein 1 on chemosensitivity of human multiforme glioblastoma cell line BT325].

BACKGROUND & OBJECTIVE: Multidrug resistance is a major reason of failure of chemotherapy for glioma. Overexpression of P-glycoprotein (P-gp), encoded by multidrug resistant protein 1 (MDR1) gene, is one of the key factors. This study was to explore the regulatory effect of small interfering RNA (siRNA) targeting MDR1 on chemosensitivity of human multiforme glioblastoma cell line BT325. METHODS: MDR1 siRNAs containing sequences of 3,051-3,069 (MDR1 A group), 502-520 (MDR1 B group), and 1,534-1,552 (MDR1 C group) were designed, and transfected into BT325 cells. Positive clones were screened with puromycin. The expression of MDR1 was measured by reverse transcription-polymerase chain reaction (RT-PCR); the expression of P-gp was detected by immunohistochemistry and flow cytometry (FCM). Drug sensitivity assay was performed in the transfected cells. RESULTS: BT325 cells proliferated exponentially after MDR1 siRNA transfection. After transfection of MDR1 siRNAs, the expression of MDR1 mRNA was significantly lower in MDR1 A, B, and C groups than in control group (0.18+/-0.05, 0.30+/-0.09, and 0.36+/-0.13 vs. 0.76+/-0.06, P<0.001); the positive rate of P-gp was decreased from 85.73% to 1.44%; the 50% inhibitory concentrations (IC(50)) of doxorubicin and vincristine to BT325 cells were decreased markedly; the G0/G1 phase proportions of MDR1 A, B, and C groups were increased by 13.55%, 14.35%, and 1.46% of control, respectively (P<0.05). CONCLUSION: MDR1 siRNA may modulate multidrug resistance through down-regulating the expression of MDR1 gene, enhancing the chemosensitivity of glioma, and inducing cell apoptosis.

[Relationship between the expression of O6-methylguanine-DNA methyltransferase in glioma and the survival time of patients].

BACKGROUND & OBJECTIVE: Previous studies showed that the DNA-repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) is one of drug resistant factors that affect chemosensibility of glioma. This study was to analyze the relationship between the expression of MGMT in glioma and the survival time of patients,and supply references to make molecular classification for glioma based on drug resistant mechanism. METHODS: MGMT expression in 311 glioma specimens was examined by tissue array technology and immunohistochemistry method, all patients had been followed up for 5 years, and the materials were analyzed statistically. RESULTS: The positive expression of MGMT was 126 in 311 gliomas (40.51%), among them, 61 in 121 astrocytomas (50.41%), 18 in 70 oligodendrogliomas (25.71%), 18 in 64 oligoastrocytomas (28.13%), 29 in 56 glioblastomas (51.79%); 68 in 186 grade I-II gliomas (36.56%), and 58 in 125 grade III-IV gliomas (46.40%). The difference of MGMT expression between grade I-II and grade III-IV gliomas was significant (P< 0.001). According to Kaplan-Meier's survival curves and log-rank test, patients with MGMT expression showed a shorter survival time than those with no MGMT expression (P< 0.05). CONCLUSION: MGMT expression in glioma correlates with histopathological type and tumor grade. Patients with MGMT expression show a shorter survival time than those with no MGMT expression.

Schwann cells transplantation promoted and the repair of brain stem injury in rats.

OBJECTIVE: To explore the possibility of Schwann cells transplantation to promote the repair of injured brain stem reticular structure in rats. METHODS: Schwann cells originated from sciatic nerves of 1 to 2-day-old rats were expanded and labelled by BrdU in vitro, transplanted into rat brain stem reticular structure that was pre-injured by electric needle stimulus. Immunohistochemistry and myelin-staining were used to investigate the expression of BrdU, GAP-43 and new myelination respectively. RESULTS: BrdU positive cells could be identified for up to 8 months and their number increased by about 23%, which mainly migrated toward injured ipsilateral cortex. The GAP-43 expression reached its peak in 1 month after transplantation and was significantly higher than that in the control group. New myelination could be seen in destructed brain stem areas. CONCLUSION: The transplantation of Schwann cells can promote the restoration of injured brain stem reticular structure.

Effect of rat Schwann cell secretion on proliferation and differentiation of human neural stem cells.

OBJECTIVE: To investigate the effect of rat Schwann cell secretion on the proliferation and differentiation of human embryonic neural stem cells (NSCs). METHODS: The samples were divided into three groups. In Group One, NSCs were cultured in DMED/F12 in which Schwann cells had grown for one day. In Group Two, NSCs and Schwann cells were co-cultured. In Group Three, NSCs were cultured in DMEM/F12. The morphology of NSCs was checked and beta-tubulin, GalC, hoechst 33342 and GFAP labellings were detected. RESULTS: In Group One, all neural spheres were attached to the bottom and differentiated. The majority of them were beta-tubulin positive while a few of cells were GFAP or GalC positive. In Group Two, neural spheres remained undifferentiated and their proliferation was inhibited in places where Schwann cells were robust. In places where there were few Schwann cells, NSCs performed in a similar manner as in Group One. In Group Three, the cell growth state deteriorated day after day. On the 7th day, most NSCs died. CONCLUSION: The secretion of rat Schwann cells has a growth supportive and differentiation-inducing effect on human NSCs.

Combination of carbamazepine and valproate in different dose proportions in maximal electroshock seizure model in mice.

Rational polypharmacy of antiepileptic drugs is one of the treatment strategies for refractory epilepsy. To investigate whether it may be rational to combine carbamazepine (CBZ) and valproate (VPA), we tested both the anti-convulsant effect and the toxicity of combinations of CBZ and VPA in different dose proportions. CBZ/VPA dose ratios were, respectively, 1:6.66, 1:10, 1:13.3 and 1:20. The median effect doses of monotherapy and polytherapy in maximal electroshock seizure test and the median lethal (within 3 days after administration) doses were determined. These parameters were analyzed with the isobologram method. We found that the anti-convulsant effect of all combinations was additive. The toxicity of combination 1, 2 and 3 (CBZ/VPA, 1:6.66, 1:10, 1:13.3) was additive, but the toxicity of combination 4 (CBZ/VPA, 1:20) was infra-additive. Thus, in mice, using this model, a combination of CBZ/VPA 1:20 has an advantage over each of the drugs alone.