Brain expression profiles of two antisense RNAs in children and adolescents with epilepsy.

Objective: Heterozygous mutations within the voltage-gated sodium channel α subunit () are responsible for the majority of cases of Dravet syndrome (DS), a severe developmental and epileptic encephalopathy. Development of novel therapeutic approaches is mandatory in order to directly target the molecular consequences of the genetic defect. The aim of the present study was to investigate whether cis-acting long non-coding RNAs (lncRNAs) of are expressed in brain specimens of children and adolescent with epilepsy as these molecules comprise possible targets for precision-based therapy approaches.

The impact of tethered recording techniques on activity and sleep patterns in rats.

Electrophysiological recordings in animals constitute frequently applied techniques to study neuronal function. In this context, several authors described tethered recordings as a semi-restraint situation with negative implications for animal welfare and suggested radiotelemetric setups as a refinement measure. Thus, we here investigated the hypothesis that tethered recordings exert measurable effects on behavioral and sleep patterns in Sprague-Dawley rats.

Development of behavioral patterns in young C57BL/6J mice: a home cage-based study.

Evidence exists that behavioral patterns only stabilize once mice reach adulthood. Detailed information about the course of behavioral patterns is of particular relevance for neuroscientific research and for the assessment of cumulative severity in genetically modified mice. The analysis considered five age groups focusing on behavioral assessments in the animals' familiar home cage environment during the adolescence phase.

Toward Evidence-Based Severity Assessment in Mouse Models with Repeated Seizures: (II.) Impact of Surgery and Intrahippocampal Kainate.

Introduction: Chronic epilepsy models require neurosurgical procedures including depth electrode implants. The intrahippocampal kainate model is a frequently used chronic paradigm, which is based on chemoconvulsant administration and status epilepticus induction during the surgical procedure. This experimental approach raises the question of the extent to which this approach affects postsurgical recovery.

Assistive technology to promote leisure and constructive engagement by two boys emerged from a minimal conscious state.

Background: Post-coma persons with multiple disabilities may represent a challenge to rehabilitation centers, due to their clinical conditions. Moreover, they can failed to engage adaptive responses aimed at the self-management of environmental stimuli.

Objectives: To assess the impact and social rating of a new assistive technology set-up for promoting constructive engagement by two post-coma boys emerged from a minimal conscious state.

Comprehensive morphometric analysis of mononuclear cell infiltration during experimental renal allograft rejection.

The role of specific subtypes of infiltrating cells in acute kidney allograft rejection is still not clear and was so far not examined by different analyzing methods under standardized conditions of an experimental kidney transplantation model. Immunohistochemical staining of CD3, CD20 and CD68 was performed in rat allografts, in syngeneically transplanted rats and in control rats with a test duration of 6 and 28 days. The detailed expression and localization of infiltrating cells were analyzed manually in different kidney compartments under light microscope and by the two different morphometric software programs.

Technology-assisted programmes to promote leisure engagement in persons with acquired brain injury and profound multiple disabilities: two case studies.

OBJECTIVE. To evaluate technology-assisted programmes for enabling a woman and a man with brain injury and profound multiple disabilities to acquire leisure engagement. METHOD.

Communication opportunities via special messaging technology for two post-coma persons with multiple disabilities.

This study extended the assessment of a special messaging technology with two additional post-coma adults who had emerged from a minimally conscious state, but showed multiple disabilities including profound motor and communication impairments. For each participant, the study involved an ABAB design, in which the A represented baseline phases and the B represented intervention phases with the special messaging technology. The technology involved a net-book computer provided with specific software, a global system for mobile communication (GSM) modem, microswitches, and prerecorded verbal lists of persons' names and messages.

Use of microswitch technology and a keyboard emulator to support literacy performance of persons with extensive neuro-motor disabilities.

Objective: To assess the effectiveness and acceptability of microswitch technology and a keyboard emulator to enable three participants with extensive neuro-motor disabilities to write words.

Method: In Study I, two participants triggered an automatic scanning keyboard and selected/wrote letters via a small sliding movement of their hand(s) activating a touch/pressure panel (microswitch). In Study II, a third participant used the sliding movement and panel and a vocalization response with a voice-detecting microswitch.

Impact of Toll-like receptor 2 expression in renal allograft rejection.

Background: An important role of TLR2 has been shown in various experimental models of renal ischaemia/reperfusion injury. To study the expression of TLR2 in renal allograft rejection systematically, we established an experimental rat transplantation model.

Methods: TLR2 expression was analysed in 99 human renal allograft biopsies, and in rat allografts at Day 6 and 28 after experimental renal transplantation.

Persons with multiple disabilities accessing stimulation and requesting social contact via microswitch and VOCA devices: new research evaluation and social validation.

The first of these two studies assessed whether 11 participants with multiple disabilities of 5.3-18.2 (M=10.

Scrapie-infected transgenic mice expressing a laminin receptor decoy mutant reveal a prolonged incubation time associated with low levels of PrPres.

The 37-kDa/67-kDa laminin receptor (LRP/LR) was identified as a cell surface receptor for prion proteins. The laminin receptor mutant LRP102-295::FLAG interfered with PrP(Sc) propagation in murine neuronal cells presumably acting as a decoy in a transdominant negative fashion by trapping PrP molecules in the extracellular matrix. Here, we generated hemizygous transgenic mice expressing LRP102-295::FLAG in the brain.

Microinjection of lentiviral vectors expressing small interfering RNAs directed against laminin receptor precursor mRNA prolongs the pre-clinical phase in scrapie-infected mice.

We examined therapeutic in vitro and in vivo approaches using lentivirus-based packaging of small interfering RNAs (siRNAs) targeting the non-integrin laminin receptor mRNA for treatment and prevention of prion disorders. Transfection of N2aSc(+) cells with recombinant plasmids expressing three different siRNAs, significantly reduced both the LRP (laminin receptor precursor) and PrP(Sc) levels by approximately 40-60 %. Stereotactic intracerebral microinjection of recombinant lentiviral vectors LVsiRNA-LRP 7 and 9 into the cortex of C57BL/6 wild-type mice resulted in a significant reduction of the LR levels in the cortex 15 days post-injection by 62 and 82 %, respectively.

Delivery of single-chain antibodies (scFvs) directed against the 37/67 kDa laminin receptor into mice via recombinant adeno-associated viral vectors for prion disease gene therapy.

The 37/67 kDa laminin receptor (LRP/LR) acts as a receptor for prions providing a promising target for the treatment of prion diseases. Recently, we selected anti-LRP/LR single-chain antibodies (scFvs) and proved a reduction of the peripheral PrP(Sc) propagation by passive immunotransfer into scrapie-infected mice. Here, we report the development of an in vivo gene delivery system based on adeno-associated virus (AAV) vectors expressing scFvs-S18 and -N3 directed against LRP/LR.

Anti-LRP/LR antibody W3 hampers peripheral PrPSc propagation in scrapie infected mice.

We identified the 37kDa/67kDa laminin receptor (LRP/LR) as a cell surface receptor for the cellular prion protein (PrP(c)) and the infectious prion protein (PrP(Sc)). Recently, we showed that anti-LRP/LR antibody W3 cured scrapie infected N2a cells. Here, we demonstrate that W3 delivered by passive immunotransfer into C57BL/6 mice reduced the PrP(Sc) content in the spleen significantly by 66%, demonstrating an impairment of the peripheral PrP(Sc) propagation.

Single chain Fv antibodies directed against the 37 kDa/67 kDa laminin receptor as therapeutic tools in prion diseases.

Transmissible spongiform encephalopathies are a group of neurological disorders associated with the deposition of PrP(Sc), an abnormal form of the cellular prion protein PrP(c). The 37 kDa/67 kDa laminin receptor (LRP/LR) has been identified as a prion receptor and several lines of evidence strongly suggest that this protein plays a role during prion pathogenesis. Here we report the selection of recombinant single chain antibodies (scFvs) directed against LRP from naïve and synthetic phage scFv libraries for therapeutic application.

Transcriptome analysis reveals altered cholesterol metabolism during the neurodegeneration in mouse scrapie model.

To identify the dynamic transcriptional alterations in CNS during the development of prion disease, brains of scrapie-infected mice and age-matched, mock-inoculated controls were analyzed immediately before inoculation and at different time points post-inoculation using Affymetrix microarray technique. A total of 449 probe sets, representing 430 genes, showed differential expression between scrapie- and mock-inoculated mice over the time course. These genes could be separated into two clusters according to expression patterns: the genes in cluster 1 demonstrated lower mRNA levels in scrapie-infected brains when compared with mock-inoculated brains, whereas genes in cluster 2 showed higher mRNA levels in scrapie-infected brains.

Mutant presenilin 1 alters synaptic transmission in cultured hippocampal neurons.

Mutations in presenilins are the major cause of familial Alzheimer disease, but the precise pathogenic mechanism by which presenilin (PS) mutations cause synaptic dysfunction leading to memory loss and neurodegeneration remains unclear. Using autaptic hippocampal cultures from transgenic mice expressing human PS1 with the A246E mutation, we demonstrate that mutant PS1 significantly depressed the amplitude of evoked alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate receptor-mediated synaptic currents. Analysis of the spontaneous miniature synaptic activity revealed a lower frequency of miniature currents but normal miniature amplitude.