Neuronal antibody prevalence in children with seizures under 3 years: A prospective national cohort.

Objective: To report the prevalence of anti-neuronal antibodies in a prospective whole-nation cohort of children presenting with seizures before their third birthday.

Methods: This was a prospective population-based national cohort study involving all children presenting with new-onset epilepsy or complex febrile seizures before their third birthday over a 3-year period. Patients with previously identified structural, metabolic, or infectious cause for seizures were excluded.

Persistent microglial activation and synaptic loss with behavioral abnormalities in mouse offspring exposed to CASPR2-antibodies in utero.

Gestational transfer of maternal antibodies against fetal neuronal proteins may be relevant to some neurodevelopmental disorders, but until recently there were no proteins identified. We recently reported a fivefold increase in CASPR2-antibodies in mid-gestation sera from mothers of children with intellectual and motor disabilities. Here, we exposed mice in utero to purified IgG from patients with CASPR2-antibodies (CASPR2-IgGs) or from healthy controls (HC-IgGs).

Fibrin As a Scaffold for Delivery of GDNF Overexpressing Stem Cells to the Adult Rat Brain.

Treatment of neurodegenerative disease is entering a new era where direct intracerebral delivery of therapeutic factors aims to restore normality to dysfunctional circuits. Cell-based therapeutic approaches, where virally manipulated mesenchymal stem cells (MSCs) overexpressing glial cell line derived neurotrophic factor (GDNF) are utilized as vehicles to deliver neurotrophic support to the Parkinsonian brain, have shown promising preclinical results at preserving dopaminergic neuron integrity. However, poor cell survival following transplantation will hinder clinical progression.

Heat shock protein 70 reduces α-synuclein-induced predegenerative neuronal dystrophy in the α-synuclein viral gene transfer rat model of Parkinson's disease.

Aims: It has become increasingly evident that the nigrostriatal degeneration associated with Parkinson's disease initiates at the level of the axonal terminals in the putamen, and this nigrostriatal terminal dystrophy is either caused or exacerbated by the presence of α-synuclein immunopositive neuronal inclusions. Therefore, strategies aimed at reducing α-synuclein-induced early neuronal dystrophy may slow or halt the progression to overt nigrostriatal neurodegeneration. Thus, this study sought to determine if adeno-associated virus (AAV) mediated overexpression of two molecular chaperone heat shock proteins, namely Hsp27 or Hsp70, in the AAV-α-synuclein viral gene transfer rat model of Parkinson's disease could prevent α-synuclein-induced early neuronal pathology.

The reduction in immunogenicity of neurotrophin overexpressing stem cells after intra-striatal transplantation by encapsulation in an in situ gelling collagen hydrogel.

Delivery of neurotrophic factors to the brain via genetically modified bone marrow-derived mesenchymal stem cells (MSCs) offers a promising neuroprotective strategy for neurodegenerative diseases. However, MSCs delivered to the CNS typically show poor survival post-transplantation, which is accompanied by microglial activation and astrocyte recruitment at the graft site. Recent studies have shown the potential of biomaterials to provide a supportive matrix for transplanted cells which may assist in the grafting process.

The neurotoxicity of gene vectors and its amelioration by packaging with collagen hollow spheres.

Over the last twenty years there have been several reports on the use of nonviral vectors to facilitate gene transfer in the mammalian brain. Whilst a large emphasis has been placed on vector transfection efficiency, the study of the adverse effects upon the brain, caused by the vectors themselves, remains completely overshadowed. To this end, a study was undertaken to study the tissue response to three commercially available transfection agents in the brain of adult Sprague Dawley rats.

Further characterisation of the LPS model of Parkinson's disease: a comparison of intra-nigral and intra-striatal lipopolysaccharide administration on motor function, microgliosis and nigrostriatal neurodegeneration in the rat.

Chronic neuroinflammation has been established as one of the many processes involved in the pathogenesis of Parkinson's disease (PD). Because of this, researchers have attempted to replicate this pathogenic feature in animal models using the potent inflammagen, lipopolysaccharide (LPS), in order to gain better understanding of immune-mediated events in PD. However, although the effect of intra-cerebral LPS on neuroinflammation and neurodegeneration has been relatively well characterised, its impact on motor function has been less well studied.

Kinetics of thermally induced heat shock protein 27 and 70 expression by bone marrow-derived mesenchymal stem cells.

Although bone marrow-derived mesenchymal stem cells (MSCs) are an attractive cell therapy candidate, their potential is limited by poor survival following transplantation. Over-expression of anti-apoptotic heat shock proteins using viral vectors can improve the survival of these cells under stressful conditions in vitro and in vivo. It is also possible to induce heat shock protein expression in many cell types by simply exposing them to a transient, nonlethal elevation in temperature.

Potential of rat bone marrow-derived mesenchymal stem cells as vehicles for delivery of neurotrophins to the Parkinsonian rat brain.

Issues related to the intra-cerebral delivery of glial cell line-derived neurotrophic factor (GDNF) have hampered its progression as a neuroprotective therapy for Parkinson's disease. Ex vivo gene therapy, where cells are virally transduced in vitro to produce a specific protein, may circumvent some of the problems associated with direct delivery of this neurotrophin to the brain. In this regard, bone marrow-derived mesenchymal stem cells (MSCs) offer an ideal cell source for ex vivo gene therapy because they are easily isolated from autologous sources, they are amenable to viral transduction and expansion in vitro, and they are hypoimmunogenic and non-tumourigenic in the brain.

Survival and immunogenicity of mesenchymal stem cells from the green fluorescent protein transgenic rat in the adult rat brain.

Background: A major technical limitation in preclinical cell replacement research is the ability to discriminate between donor and host tissue after transplantation. This problem has been lessened by the availability of transgenic animals that express "reporter" genes, such as green fluorescent protein (GFP).

Objective: We determined the usefulness of one such transgenic reporter rat to assess the survival of bone marrow-derived rat mesenchymal stem cells (MSCs) following direct transplantation into the intact adult brain.

Further validation of the corridor task for assessing deficit and recovery in the hemi-Parkinsonian rat: restoration of bilateral food retrieval by dopamine receptor agonism.

The corridor test is a newly developed test of sensorimotor integration that depends on a rat's ability to retrieve food from either side of its body. Rats with unilateral dopamine-depleting lesions neglect food on the contralateral side of their bodies, and selectively retrieve from the ipsilateral side. In the present study, the time-course for development of this deficit after injection of 6-hydroxydopamine into the striatum is determined using the corridor test.