We analysed acute and long-term effects of the N-methyl-d-aspartate receptor antagonist MK-801 on long-term heterosynaptic population spike depression (LTHPSD) evoked by high-frequency stimulation of the direct cortical input in female rat hippocampal slices to understand disturbances in cognitive functions associated with an acute phencyclidine-induced psychosis. High-frequency stimulation (HFS) of the direct cortical input (dCI) to cornu ammonis area 1 (CA1) induced homosynaptic long-term potentiation (LTP) while simultaneously evoking LTHPSD at the Schaffer collateral input. Animals treated with a single intraperitoneal application of MK-801 (5 mg/kg body weight) showed severe behavioural alterations for 24 h, although histological examination of CA1 did not reveal any morphological changes. However, after application of MK-801, homosynaptic LTP of the dCI was suppressed for up to 7 days and recovered within 4 weeks. Likewise, LTHPSD in response to HFS of the dCI to CA1 was abolished for at least 1 week post-treatment, with partial recovery occurring after 4 weeks. Homosynaptic LTP, induced by HFS of Schaffer collaterals, was also disturbed for at least 24 h, with recovery after 7 days. Remarkably, bath application of MK-801 (50 microM) converted LTHPSD, induced by dCI HFS, into persistent heterosynaptic long-term enhancement of stratum radiatum-evoked responses. The acute effects of MK-801 on synaptic plasticity seen in this study may contribute to the observed severe behavioural alterations and long-term effects and may explain some of the long-lasting symptoms remaining after an acute psychotic episode in humans.

BackgroundA decrease of small nerve fibers in skin biopsies during the course of critical illness has been demonstrated recently. However, the diagnostic use of skin biopsies in sepsis and its time course is not known.MethodsPatients (n=32) with severe sepsis or septic shock were examined using skin biopsies, neurological examination, nerve conduction studies, and sympathetic skin response in the first week after onset of sepsis, 2 weeks and 4 months later and compared to gender- and age-matched healthy controls.ResultsSkin biopsies at the ankle and thigh revealed a significant decrease of intraepidermal nerve fiber density (IENFD) during the first week of sepsis and 2 weeks later. All patients developed critical illness polyneuropathy (CIP) according to electrophysiological criteria and 11 showed IENFD values lower than the 0.05 quantile. Four patients were biopsied after 4 months and still showed decreased IENFD. Results of nerve conduction studies and IENFD did considerably change over time. No differences for survival time between patients with IEFND lower and larger than 3.5 fibers/mm were found.ConclusionsSkin biopsy is able to detect an impairment of small sensory nerve fibers early in the course of sepsis. However, it may not be suited as a prognostic parameter for survival.Trial registrationGerman Clinical Trials Register, DRKS-ID: DRKS00000642, 12/17/2010Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1241-5) contains supplementary material, which is available to authorized users.

There is a need for easy-to-use molecular assays for diagnosis of invasive meningococcal disease. Here, we report the rapid identification of Neisseria meningitidis in a cerebrospinal fluid sample from a patient with purulent meningitis using a commercially available loop-mediated isothermal amplification assay, resulting in a prompt de-escalation of the initial empiric antibiotic therapy.