The mRNA levels of NKCC1, an inwardly directed Na ⁺ , K ⁺ -2Cl ⁻ cotransporter that facilitates the accumulation of intracellular Cl ⁻ , and of KCC2, an outwardly directed K ⁺ -Cl ⁻ cotransporter that extrudes Cl ⁻ , were studied in surgically resected brain specimens from drug-resistant temporal lobe (TL) epilepsy (TLE) patients. Quantitative RT-PCR analyses of the mRNAs extracted from the human TLE-associated brain regions revealed an up-regulation of NKCC1 mRNA and a down-regulation of KCC2 mRNA in the hippocampal subiculum, compared with the hippocampus proper or the TL neocortex, suggesting an abnormal transcription of Cl ⁻ transporters in the TLE subiculum. In parallel experiments, cell membranes isolated from the same TLE-associated brain regions were injected into Xenopus oocytes that rapidly incorporated human GABA _A receptors into their surface membrane. The GABA currents elicited in oocytes injected with membranes from the subiculum had a more depolarized reversal potential ( E _GABA ) compared with the hippocampus proper or the neocortex. The NKCC1 blocker bumetanide or a temperature decrease of 10°C shifted the GABA-current E _GABA more negative in oocytes injected with membranes from TLE hippocampal subiculum, matching the E _GABA of TL neocortex-injected oocytes. We conclude that the anomalous expression of both Cl ⁻ transporters, KCC1 and NKCC2, in TLE hippocampal subiculum probably causes altered Cl ⁻ transport in the “epileptic” neurons, as revealed in the microtransplanted Xenopus oocytes, and renders GABA aberrantly “exciting,” a feature that may contribute to the precipitation of epileptic seizures.

Cell migration and invasion are highly regulated processes involved in both physiological and pathological conditions. Here we show that autophagy modulation regulates the migration and invasion capabilities of glioblastoma (GBM) cells. We observed that during autophagy occurrence, obtained by nutrient deprivation or by pharmacological inhibition of the mTOR complexes, GBM migration and chemokine‐mediated invasion were both impaired. We also observed that SNAIL and SLUG, two master regulators of the epithelial–mesenchymal transition (EMT process), were down‐regulated upon autophagy stimulation and, as a consequence, we found a transcriptional and translational up‐regulation of N‐ and R‐cadherins. Conversely, in BECLIN 1‐silenced GBM cells, an increased migration capability and an up‐regulation of SNAIL and SLUG was observed, with a resulting decrease in N‐ and R‐cadherin mRNAs. ATG5 and ATG7 down‐regulation also resulted in an increased migration and invasion of GBM cells combined to an up‐regulation of the two EMT regulators. Finally, experiments performed in primary GBM cells from patients largely confirmed the results obtained in established cell cultures.Overall, our results indicate that autophagy modulation triggers a molecular switch from a mesenchymal phenotype to an epithelial‐like one in GBM cellular models. Since the aggressiveness and lethality of GBM is defined by local invasion and resistance to chemotherapy, we believe that our evidence provides a further rationale for including autophagy/mTOR‐based targets in the current therapeutical regimen of GBM patients.

From 1976 to 1986, 681 patients with drug-refractory trigeminal neuralgia (TN)—typical in 641, symptomatic of multiple sclerosis in 23 and of tumor in 10, atypical in 5, and postherpetic in 2—were treated with various percutaneous procedures. Controlled differential thermocoagulation of the gasserian ganglion and/or retrogasserian rootlets was performed in 533 patients; glycerolization of the trigeminal cistern in 32; and compression of the gasserian ganglion by balloon catheter in 159, Results and complications of each procedure are assessed at a mean follow-up of 6.5 years for thermocoagulation, 5 years for glycerolization, and 3.5 years for compression. The following therapeutic protocol is proposed: 1) in TN patients at first operation: a) gasserian compression (or glycerolization, if experience warrants it) is indicated in all cases of typical TN, unless the 3rd division alone is affected; b) in the latter case and in symptomatic TN, we suggest thermocoagulation; 2) in recurrences: a) after glycerolization or gasserian compression, gasserian compression (or glycerolization) is indicated; b) after thermocoagulation or open surgery, thermocoagulation is suggested.