Microglia-neuron interaction at nodes of Ranvier depends on neuronal activity through potassium release and contributes to remyelination.

Microglia, the resident immune cells of the central nervous system, are key players in healthy brain homeostasis and plasticity. In neurological diseases, such as Multiple Sclerosis, activated microglia either promote tissue damage or favor neuroprotection and myelin regeneration. The mechanisms for microglia-neuron communication remain largely unkown. Here, we identify nodes of Ranvier as a direct site of interaction between microglia and axons, in both mouse and human tissues. Using dynamic imaging, we highlight the preferential interaction of microglial processes with nodes of Ranvier along myelinated fibers. We show that microglia-node interaction is modulated by neuronal activity and associated potassium release, with THIK-1 ensuring their microglial read-out. Altered axonal K+ flux following demyelination impairs the switch towards a pro-regenerative microglia phenotype and decreases remyelination rate. Taken together, these findings identify the node of Ranvier as a major site for microglia-neuron interaction, that may participate in microglia-neuron communication mediating pro-remyelinating effect of microglia after myelin injury.

[Fentanyl in peridural obstetrical analgesia. Evaluation after 4 years' use]. / Le fentanyl dans l'analgésie obstétricale par voie péridurale. Bilan après quatre ans d'utilisation.

7,500 deliveries occurred from the date of opening of the Maternity Hospital Jean-Rostand. 3,500 of these were conducted under epidural anaesthesia. At different stages prospective studies were carried out to recall the effect of adding fentanyl to bupivacaine when the epidural injection was made. A pharmacokinetic study. This shows that the levels in the mother and the fetus begin to coincide more with the number of doses that are given and pass from 0.3 after 50 micrograms have been administered to 0.5 after 100 micrograms have been administered and 0.7 after 150 micrograms have been administered. The fetal levels are far lower than those required to depress respiration. The half life of distribution through the circulation has been worked out at 4 minutes and the half for elimination of the drug at 460 minutes. The maternal levels show great fluctuations and late alterations. Analgesia is earlier, more complete and more prolonged when fentanyl is added. Fentanyl also masks irregularities. Undesirable effects such as tiredness, pruritus, nausea, vomiting and urinary retention occur infrequently and last only for short periods of time. No mother had respiratory depression. The doses of bupivacaine that had to be given were as a whole less when fentanyl was added. In 40% of cases it only required one injection to achieve analgesia throughout the whole labour. The length of labour and the number of caesarean operations carried out did not change.(ABSTRACT TRUNCATED AT 250 WORDS)