The role of neural cell adhesion molecules in plasticity and repair.

Repair and functional recovery after brain injury critically depends on structural and functional plasticity of preserved neuronal networks. A striking feature of brain structures where tissue reorganization and plasticity occur is a strong expression of the polysialylated neural cell adhesion molecule (PSA-NCAM). An important role of this molecule in various aspects of neuronal and synaptic plasticity has been revealed by many studies. Recently, a new mechanism has been elucidated whereby PSA-NCAM may contribute to signalling mediated by the neurotrophic factor BDNF, thereby sensitizing neurons to this growth factor. This mechanism was shown to be important for activity-induced synaptic plasticity and for the survival and differentiation of cortical neurons. A cross-talk between these molecules may, thus, reveal a key factor for properties of structural plasticity and in particular could mediate the activity-dependent aspects of synaptic network remodeling. Animal models have been developed to assess the role of these molecules in functional recovery after lesions.

Transgene expression of plasmid DNAs directed by viral or neural promoters in the rat brain.

The use of circular plasmid DNA may be an alternative method for the transfer of genes into the brain and is presumably easier to use than other vectors, such as viruses or genetically engineered cells. The effectiveness and time course of the expression of a reporter gene (LacZ), directed by appropriate promoters, was studied after stereotaxic injection of naked plasmid DNAs into the rat thalamus, cortex or cerebellum. The efficiencies of three different promoters, the human cytomegalovirus (HCMV) promoter and the glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE) promoters (specific for astrocytes and neurons, respectively) to drive reporter gene expression were compared. Efficient expression of beta-gal, detected by X-gal histochemistry or immunochemistry, required the use of 50 microg of DNA and was detectable as early as 48 h after injection. Expression increased until day 8, remained stable until day 15, then decreased over 2 months, probably as a result of non-specific degradation of the plasmids within the transfected cells rather than from specific down-regulation of promoters, as the same time course was seen with all three promoters tested. Depending on the promoter used (GFAP or NSE), LacZ was preferentially expressed within astrocytes or neurons, respectively. The GFAP promoter was found to be as efficient as the HCMV promoter, possibly due to the reactive gliosis induced by plasmid injection which is known to up-regulate GFAP expression.

Comparison of Epstein-Barr virus markers in Reed-Sternberg cells in adult Hodgkin's disease tissues from an industrialized and a developing country.

The link between Hodgkin's disease (HD) and Epstein-Barr virus (EBV) is well documented in childhood and here the same hypothesis has been examined in adults, by comparing cases from an industrialized and a developing country. In this study the prevalence of EBV markers in nodal lesions of adult HD were compared in 21 patients from France (Fr) and 25 from Algeria (Al), all clinically staged during 1990-1992. Median age was 29 years. Histologic subtypes included lymphocytic predominance (LP) Fr 1; nodular sclerosis (NS) Fr 16, Al 16; mixed cellularity (MC) Fr 4, Al 9. EBV markers examined included expression of latent membrane protein (LMP) in Reed-Sternberg and Hodgkin cells (RSC) by immunochemistry; EBV-DNA and -RNA in situ hybridization (ISH); EBV-DNA by polymerase chain reaction (PCR). Results showed that RSC were LMP-positive in 4 (2 NS, 2 MC) French and 7 (3 NS, 4 MC) Algerian. All LMP+ cases were also positive for EBV DNA-RNA ISH. ISH was positive in RSC of 33% of the French and 72% of Algerian patients (p < 0.02). The positivity was more frequent in MC (77%) than in other histologic types (45%). The EBV genome was detected by PCR on DNA extracted from frozen samples in 84% of Fr and 95% of Al patients (100% of MC and 86% of other histologic types). Conclusion. The discrepancy between PCR and ISH results may be due to the lesser sensitivity of the ISH technique, or, alternatively, to the presence of EBV in the lymphoid cells surrounding RSC.(ABSTRACT TRUNCATED AT 250 WORDS)

[Association of Epstein-Barr virus and Hodgkin's disease: comparison between Algerian and French patients]. / Association du virus d'Epstein-Barr à la maladie de Hodgkin: comparaison entre patients algériens et français.

The prevalence of Epstein-Barr virus (EBV) markers in nodal lesions from Algerian (Al) patients (n = 47) was compared to French (Fr) patients (n = 21) with Hodgkin's disease. Initial characteristics were: males Fr 57%, Al 53%; median age Fr 29, Al 26; histologic subtypes: lymphocytic predominance (LP) Fr 1, Al 2; nodular sclerosis (NS) Fr 16, Al 19; mixed cellularity (MC) Fr 4, Al 12; lymphocytic depletion (LD) Al 2. The latent membrane protein (LMP) was expressed in Reed-Sternberg cells (RSC) in 16 Al (4 NS, 12 MC) and 4 Fr (2 NS, 2 MC) cases. All LMP-positive cases were also positive by DNA or RNA in situ hybridization (ISH). ISH was positive in RSC of 29% of Fr and 66% of Al patients (p < 0.02); the positivity was more frequent in MC (80%) than in other histologic types (39%). EBV genome was detected by PCR on DNA extracted from frozen samples in 84% of Fr and 95% of Al patients (100% of MC and 86% of other histologic types). The discrepancy between PCR and ISH results can be due to a lesser sensitivity of the latter technique, or, alternatively, to the presence of EBV in lymphoid cells surrounding RSC. ISH positivity was more frequent in young Al adults than in Fr ones. This more pronounced HD-EBV link in patients from a developing country compared with an industrialized one can result from the age at primary EBV infection, which occurs earlier in Algeria than in France.