Differentiation renders susceptibility to excitotoxicity in HT22 neurons.

HT22 is an immortalized mouse hippocampal neuronal cell line that does not express cholinergic and glutamate receptors like mature hippocampal neurons in vivo. This in part prevents its use as a model for mature hippocampal neurons in memory-related studies. We now report that HT22 cells were appropriately induced to differentiate and possess properties similar to those of mature hippocampal neurons in vivo, such as becoming more glutamate-receptive and excitatory. Results showed that sensitivity of HT22 cells to glutamate-induced toxicity changed dramatically when comparing undifferentiated with differentiated cells, with the half-effective concentration for differentiated cells reducing approximately two orders of magnitude. Moreover, glutamate-induced toxicity in differentiated cells, but not undifferentiated cells, was inhibited by the N-methyl-D- aspartate receptor antagonists MK-801 and memantine. Evidently, differentiated HT22 cells expressed N-methyl-D-aspartate receptors, while undifferentiated cells did not. Our experimental findings indicated that differentiation is important for immortalized cell lines to render post-mitotic neuronal properties, and that differentiated HT22 neurons represent a better model of hippocampal neurons than undifferentiated cells.

A study of radiation-induced cerebral vascular injury in nasopharyngeal carcinoma patients with radiation-induced temporal lobe necrosis.

PURPOSE: To investigate radiation-induced carotid and cerebral vascular injury and its relationship with radiation-induced temporal lobe necrosis in nasopharyngeal carcinoma (NPC) patients. METHODS AND MATERIALS: Fifty eight NPC patients with radiation-induced temporal lobe necrosis (TLN) were recruited in the study. Duplex ultrasonography was used to scan bilateral carotid arterials to evaluate the intima-media thickness (IMT) and occurrence of plaque formation. Flow velocities of bilateral middle cerebral arteries (MCAs), internal carotid arteries (ICAs) and basal artery (BA) were estimated through Transcranial Color Doppler (TCD). The results were compared with data from 33 patients who were free from radiation-induced temporal lobe necrosis after radiotherapy and 29 healthy individuals. RESULTS: Significant differences in IMT, occurrence of plaques of ICAs and flow velocities of both MCAs and ICAs were found between patients after radiotherapy and healthy individuals (p<0.05). IMT had positive correlation with post radiation interval (p = 0.049). Compared with results from patients without radiation-induced TLN, the mean IMT was significantly thicker in patients with TLN (p<0.001). Plaques were more common in patients with TLN than patients without TLN (p = 0.038). In addition, flow velocities of MCAs and ICAs in patients with TLN were much faster (p<0.001, p<0.001). Among patients with unilateral TLN, flow velocity of MCAs was significantly different between ipsilateral and contralateral sides to the lesion (p = 0.001). CONCLUSION: Thickening of IMT, occurrence of plaque formation and hemodynamic abnormality are more common in patients after radiotherapy, especially in those with TLN, compared with healthy individuals.

Kallikrein gene transfer induces angiogenesis and further improves regional cerebral blood flow in the early period after cerebral ischemia/reperfusion in rats.

AIMS: The aims of this study were to find out whether kallikrein could induce angiogenesis and affect the cerebral blood flow (rCBF) in the early period after cerebral ischemia/reperfusion (CI/R). METHODS: The adenovirus carried human tissue kallikrein (HTK) gene was administrated into the periinfarction region after CI/R. At 12, 24, and 72 h after treatments, neurological deficits were evaluated; expression of HTK and vascular endothelial growth factor (VEGF) were detected by immunohistochemistry staining; the infarction volume was measured; and rCBF was examined by( 14) C-iodoantipyrine microtracing technique. RESULTS: The expression of VEGF was enhanced significantly in pAdCMV-HTK group than controls over all time points (P < 0.05). Furthermore, the rCBF in pAdCMV-HTK group increased markedly than controls at 24 and 72 h after treatment (P < 0.05), and the improved neurological deficit was accompanied by reduced infarction volume in pAdCMV-HTK group 24 and 72 h posttreatment. CONCLUSION: In the early period after CI/R, kallikrein could induce the angiogenesis and improve rCBF in periinfarction region, and further reduce the infarction volume and improve the neurological deficits.

The clinical presentation and imaging manifestation of psychosis and dementia in general paresis: a retrospective study of 116 cases.

In recent years, occurrence of "general paresis (GP)" has increased significantly because of the increasing incidence of syphilis in China. Early diagnosis plays a very important role for effective treatment. Incidence is becoming extensive enough to warrant an updated investigation of the clinical characteristics of GP. The authors retrospectively reviewed 116 cases of GP in Guangzhou, China, and analyzed its incidence and clinical appearance, as well as the characteristics of EEG, neuroradiology, serum, and cerebrospinal fluid examinations. Of the 116 GP patients, clinical symptoms presented frequently on admission were a variety of psychiatric-behavioral symptoms and varying degrees of dementia. Positive sucking reflex was the most common sign, as well as hyperreflexia and Argyll-Robertson pupil. EEG data mainly showed slightly abnormal EEG activity, with increased δ waves. Focal atrophy in one or multiple cerebral regions was evident on neuroimage. The prevalence of GP extends to various social strata or classes, with clinical presentation varying considerably among patients. For patients with progressive cognitive and behavioral deterioration, accompanied with psychotic and/or affective behavioral disorders or cerebral atrophy of unknown cause, general paresis should be considered.

Relationship between individual radiosensitivity and radiation encephalopathy of nasopharyngeal carcinoma after radiotherapy.

PURPOSE: To analyze the relationship between individual radiosensitivity and the morbidity and severity of radiation encephalopathy (RE) induced by radiotherapy of nasopharyngeal carcinoma (NPC) patients. PATIENTS AND METHODS: In this study, 26 patients with RE (experimental group) and 26 patients without RE (control group) after radiotherapy of NPC were included. The experimental group was divided into two subgroups, that is, group 1 with 1-2 grade and group 2 with 3-4 grade, according to the RTOG/EORTC Score. Individual radiosensitivity was determined by the total chromosomal aberration rate measured in in vitro irradiated lymphocytes by a metaphase detection technique. Chromosomal aberration rate was correlated to development of RE in order to investigate the relationship between radiosensitivity and RE. RESULTS: The total chromosomal aberration rate was found to be a risk factor for the onset of RE. The total chromosomal aberration rate was positively correlated to the severity of RE. Patients with a high radiosensitivity had shorter latency than those with a low or intermediate radiosensitivity. CONCLUSION: In NPC patients, individual radiosensitivity as determined by the proportion of lethal chromosomal aberrations in in vitro irradiated lymphocytes might be associated with the development of RE and has the potential to predict the morbidity and severity of RE.

Treatment of Parkinson disease with C17.2 neural stem cells overexpressing NURR1 with a recombined republic-deficit adenovirus containing the NURR1 gene.

To study the potential benefit of the NURR1 gene in Parkinson's disease (PD), we constructed a recombinant republic-deficit adenovirus containing the NURR1 gene (Ad-NURR1) and expressed it in transplanted neural stem cells (NSC). Ad-NURR1 was constructed, and NURR1 mRNA and protein expression were identified by in situ hybridization and western blot analysis, respectively. The identified NURR1 protein could directly or indirectly induce NSC differentiation into neurons. To identify a potential therapeutic use for the transfected NSCs, cells were transplanted into 6-hydroxydopamine lesioned rats. Histopathological and behavioral alterations were evaluated via immunohistochemistry and the ration test, respectively, in rats transplanted with NSCs with or without the Ad-NURR1 adenovirus. The Ad-NURR1 construct effectively expressed the NURR1 protein, which could directly or indirectly induce NSC differentiation into neurons. Both histopathological and behavioral alterations were seen in rats treated with NSCs with or without the Ad-NURR1 construct, although in the case of the latter, the benefits were more robust. These results suggest a potential therapeutic benefit for Ad-NURR1-expressing cells in the treatment of PD. The Ad-NURR1 modification induced NSC differentiation and therefore represents a potential therapy for PD.

Recombinant adenovirus-mediated vascular endothelial growth factor gene transfer attenuates hypoxia-induced apoptosis of neural stem cells in vitro.

OBJECTIVE: To study the effects of vascular endothelial growth factor (VEGF) gene transfer on hypoxia-induced apoptosis of neural stem cells in vitro. METHODS: C17.2 neural stem cells cultured in vitro were infected by recombinant adenovirus containing VEGF gene and cultured under hypoxic condition. VEGF expression in these cells was detected by Western blotting, and the apoptotic index was calculated from results of triphosphate-biotin nick end-labeling (TUNEL) assay. Flow cytometry was employed to examine the changes in the cell apoptotic rate after VEGF gene transfer, and the apoptotic bodies were observed under fluorescence microscope with Hoechst33342 staining. RESULTS: The expression of VEGF was significantly increased in pAdCMV VEGF(165)-infected cells, resulting in inhibition of the apoptosis of C17.2 neural stem cells induced by hypoxia manifested by a significantly lower apoptotic rate of the stem cells transfected by pAdCMV VEGF(165) than that of the untransfected cells (10.38%;+/-0.48%; vs 19.98 %;+/-0.55%;, P<0.01) and of the cells transfected with pAdCMV VEGF(165) along with VEGF anti-sense oligodeoxynucleotide (19.07%;+/-0.64%;, <0.01) after hypoxia. CONCLUSIONS: Recombinant adenovirus can efficiently mediate VEGF gene transfer into C17.2 neural stem cells, resulting in high expression of the exogenous VEGF in vitro, which effectively reduces C17.2 neural stem cell apoptosis induced by hypoxia.