Nicotine contributes to the neural stem cells fate against toxicity of microglial-derived factors induced by Aß via the Wnt/ß-catenin pathway.

Recent studies have demonstrated that the molecules secreted from microglias play important roles in the cell fate determination of neural stem cells (NSCs), and nicotinic acetylcholine receptor agonist treatment could reduce neuroinflammation in some neurodegenerative disease models, such as Alzheimer's disease (AD). However, it is not clear how nicotine plays a neuroprotective role in inflammation-mediated central nervous diseases, and its possible mechanisms in the process remain largely elusive. The aim of this study is to improve the survival microenvironment of NSCs co-cultured with microglias in vitro by weakening inflammation that mediated by accumulation of ß-amyloid peptide (Aß). The viability, proliferation, differentiation, apoptosis of NSCs and underlying mechanisms associated with Wnt signaling pathway were investigated. The results showed that Aß could directly damage NSCs. Furthermore, concomitant to elevated levels of TNF-α, IL-1ß derived from microglias, the NSCs had been damaged more severely with the upregulation of Axin 2, p-ß-catenin and the downregulation of ß-catenin, p-GSK-3ß, microtubule-associated protein-2, choline acetyltransferase. However, addition of 10 µmol/L nicotine before microglias treated with Aß was beneficial to protect the NSCs against neurotoxicity of microglial-derived factors induced by Aß, which partially rescued proliferation, differentiation and inhibited apoptosis of NSCs via activation of Wnt/ß-catenin pathway. Taken together, these data imply that low concentration nicotine attenuates NSCs injury induced by microglial-derived factors via Wnt signaling pathway. Thus, treatment with nicotinic acetylcholine receptor agonist provides a promising research field for neural stem cell fate and therapeutic intervention in neuroinflammation diseases.

Stereotactic neurosurgical technique and electrophysiological study in ablating the ventromedial shell of the nucleus accumbens.

OBJECTIVE: To describe in as much detail as possible the method for ablating the ventromedial shell of the nucleus accumbens (NAc) and investigate the efficacy and safety of the ablation treatment. METHODS: Sixty-five patients with drug addictions received operations within the time frame from 2004 to 2009. The ablation targets were located in the bilateral medial posterior inferior shell of the NAc. Intraoperative electrophysiological monitoring was performed. RESULTS: Tissue impedance in the shell of the NAc varied from 185 to 355 Ω. When stimulated with a low frequency (2 Hz) and a voltage above 3 V, 57 out of 65 (87.7%) patients experienced slight throbbing sensations. During the lesion procedure, fever was detected on the head and face of 59 patients (90.8%), the heart rate decreased in 19 cases (29.2%), and restlessness, irritability and hyperalgia were noted for all patients. Among the 65 patients, 52 (80%) no longer experienced a psychological craving for the drug. CONCLUSIONS: The shell of the NAc may be a promising surgical target for psychosurgery. Electrophysiological recordings revealed that the shell is indeed an appropriate structure.

[Effect of imatinib at different concentrations on rat C6 glioma cell apoptosis and cell cycle].

OBJECTIVE: To investigate the effect of imatinib on rat C6 glioma cell apoptosis and cell cycle. METHODS: MTT assay was used to determine the OD value of C6 glioma cells following treatment with imatinib at different concentrations (0.156, 10 and 15 micromo/L) for 24, 48 and 72 h. The cell apoptosis was assayed by Hochest/PI staining and the cell cycle changes were analyzed by flow cytometry. RESULTS: Imatinib treatment resulted in increased number of apoptotic cells in a time- and dose-dependent manner. A 72-h treatment of the cells with imatinib at 10 and 15 micromo/L caused increased cell percentage in G(0)/G(1) phase to (68.53-/+0.83)% and (70.41-/+0.62)%, (P<0.01), decreased the percentage of G(2) phase cells to (14.48-/+0.12)% and (13.84-/+2.86)% (P<0.01), and decreased the percentage of S phase cells to (16.98-/+0.72)% and (15.78-/+2.28)%, respectively (P<0.01). CONCLUSION: Imatinib can induce apoptosis and affect the distribution of the cell cycle of C6 cells in vitro.

[Proton magnetic resonance spectroscopic imaging of the hippocampus in schizophrenia patients before and after surgery].

OBJECTIVE: To explore the features of proton magnetic resonance spectroscopy (1H-MRS) of the hippocampus in schizophrenia patients before and after stereotactic neurosurgery. METHODS: 1H-MRS was performed to determine NAA/Cr and CHO/Cr ratios on the bilateral hippocampal regions before and after stereotactic neurosurgery in 20 schizophrenia patients, with 20 healthy individuals as the controls. RESULTS: The NAA/Cr ratio in the hippocampal regions was significantly lower and the CHO/Cr ratio significantly higher in schizophrenia patients before the surgery than in the healthy controls (P<0.01). The NAA/Cr and CHO/Cr ratios in the hippocampal regions underwent no significant changes in the patients after the surgeries (P>0.05). CONCLUSION: Neuronal and cell membrane metabolism impairment is present in the hippocampus of schizophrenia patients, and stereotactic neurosurgery does not produce obvious adverse effects on the cell membrane metabolism in the hippocampus of the patients.

[Histomorphology of angiogenesis patterns in different areas of human astrocytomas].

OBJECTIVE: To study angiogenesis patterns in the edematous area and the center of human astrocytomas by histological observation, and to reveal histological basis of vasculogenic mimicry. METHOD: Tissue samples were drawn from the tumor center and the edematous area in 51 patients with human astrocytomas during operation MR and were examined by CD34 endothelial marker periodic acid-Schiff (PAS) dual staining. RESULTS: Vessels or capillaries stained by both PAS and CD34 were found in edematous areas of human astrocytomas. Besides vessels or capillaries stained by both PAS and CD34, vasculogenic mimicries (PAS-positive and CD34-negative tubes containing red blood cells and lined by neoplastic cells), PAS-positive and CD34-negative tubes containing red blood cells and without cells around, PAS-positive and partial CD34-positive vessels or capillaries, and PAS-positive and CD34-negtive vessels or capillaries were detected in the center of tumor of 4 human glioblastomas. CONCLUSIONS: Vasculogenic mimicries in the center of some high-grade astrocytomas may be caused by blood capillary dysplasia, while angiogenesis patterns are vessels or capillaries in the edematus area and the center of most human astrocytomas.

[Ultrastructural features of cultured rat cortical astrocytes with stretch-induced injury].

OBJECTIVE: To investigate the changes of ultrastructural features of cultured rat cortical astrocytes after stretch-induced injury. METHODS: Rat cortical astrocytes isolated from 1- to 2-day-old rats were cultured till confluency, and then plated in tissue culture wells with flexible silastic bottom after purification. A computer-controlled device was used to produce stretch-induced injury in the astrocytes with the imposed pressure of 50, 150, and 250 kPa respectively, followed by observation of the ultrastructural changes in the astrocytes with light and electron microscopy. RESULTS: Obvious ultrastructural destruction of the astrocytes occurred when the imposed stretch pressure was 50 kPa, and scanning electron microscopy demonstrated increased intercellular space and laceration of the cell body and its processes. Transmission electron microscopy revealed mitochondria swelling 1 h after stretch-induced injury and 6 h after the injury, vacuolar degeneration of the mitochondria occurred. Increased stretch pressure caused further decrease in the amount of glial filaments and densification of astrocytes. CONCLUSIONS: Stress, even at a relatively small scale, can cause disruption of intercellular juncture and ultrastructural change of the cultured astrocyte, which may be related with extensive brain edema after traumatic brain injury.

Radiosurgical treatment of intractable epilepsy with low radiation dose.

OBJECTIVE: To localize the epileptic foci with positron emission tomography (PET), and study the principles of target definition and method to determine the optimal range of exposure in radiosurgery for intractable epilepsy. METHODS: This study included 176 patients with intractable epilepsy, who received linear accelerator radiosurgery after (18)F-FDG PET for epileptic foci localization. The patients were divided according to different peripheral doses used in the treatment into Group A in which radiation dose of 9 to 11 Gy was used, Group B with 11 to 13 Gy and Group C with exposure to over 13 Gy. Follow-up study was conducted in all the patients for a period ranging from 3 to 16 months, during which the frequency of seizure after treatment was recorded to evaluate the therapeutic effect. RESULTS: The seizure frequency significantly decreased after radiosurgical treatment in all the groups, but between the groups, the decrement evinced no significant difference. According to Wieser's classification of the effect after operation, 46.9% cases belonged to grade I to II and 41.5% to grade III to IV. Obvious complications were not observed, nor did disability or mortality occurred in these cases. CONCLUSIONS: Stereotactic radiosurgery with low radiation dose under the guidance of PET provides a safe, effective and minimally invasive surgical approach for patients with intractable epilepsy, and peripheral radiation doses of 9 to 11 Gy for the epileptic foci localized by PET is sufficient to ensure good clinical outcome.

Association of epileptiform activity with neuronal death in the CA3 subfield of the hippocampus following focally evoked limbic seizures.

OBJECTIVE: To investigate the relationnship between epileptiform activity and cell death in the CA3 subfield of hippocampus following focally evoked limbic seizures through a quantitative study. METHODS: Wistar rats used in this study received intra-amygdaloid injection of kainic acid to induce type epileptiform activity of different duration with continuous electroencephalographic (EEG) monitoring. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was used to detect apoptotic cells. The number of CA3 neurons survived and TUNEL-positive cells were counted to estimate the number of necrotic cells. RESULTS: Epileptiform activity induced necrosis in the major form of apoptosis of the cells in CA3 subfield of the hippocampus following focally evoked limbic seizures. The longer the type epileptiform activity lasted, the less neurons survived, with consequent increase in the number of both necrotic and apoptotic cells. CONCLUSION: Prolongation of type IV seizures dose-dependently causes increase in apoptotic and necrotic cells in CA3 subfield of the hippocampus.