Tauroursodeoxycholic Acid Reduces Neuroinflammation but Does Not Support Long Term Functional Recovery of Rats with Spinal Cord Injury.

The bile acid tauroursodeoxycholic acid (TUDCA) reduces cell death under oxidative stress and inflammation. Implants of bone marrow-derived stromal cells (bmSC) are currently under investigation in clinical trials of spinal cord injury (SCI). Since cell death of injected bmSC limits the efficacy of this treatment, the cytoprotective effect of TUDCA may enhance its benefit.

Molecular and behavioural abnormalities in the FUS-tg mice mimic frontotemporal lobar degeneration: Effects of old and new anti-inflammatory therapies.

Genetic mutations in FUS, a DNA/RNA-binding protein, are associated with inherited forms of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). A novel transgenic FUS[1-359]-tg mouse line recapitulates core hallmarks of human ALS in the spinal cord, including neuroinflammation and neurodegeneration, ensuing muscle atrophy and paralysis, as well as brain pathomorphological signs of FTLD. However, a question whether FUS[1-359]-tg mouse displays behavioural and brain pro-inflammatory changes characteristic for the FTLD syndrome was not addressed.

Why do anti-inflammatory signals of bone marrow-derived stromal cells improve neurodegenerative conditions where anti-inflammatory drugs fail?

Neurodegenerative disorders share the final degenerative pathway, the inflammation-induced apoptosis and/or necrosis, irrespective of their etiology, be it of acute and chronic traumatic, vascular and idiopathic origin. Although disease-modifying strategies are an unmet need in these disorders, lately, (pre)clinical studies suggested favorable effects after an intervention with bone marrow-derived stromal cells (bm-SC). Recent interventions with intrathecal transplantation of these cells in preclinical rodent models improved the functional outcome and reduced the inflammation, but not anti-inflammatory drugs.

Treatment of rats with spinal cord injury using human bone marrow-derived stromal cells prepared by negative selection.

Background: Spinal cord injury (SCI) is a highly debilitating pathology without curative treatment. One of the most promising disease modifying strategies consists in the implantation of stem cells to reduce inflammation and promote neural regeneration. In the present study we tested a new human bone marrow-derived stromal cell preparation (bmSC) as a therapy of SCI.

Neuro-Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice.

Aims: Mutations in DNA/RNA-binding factor (fused-in-sarcoma) FUS and superoxide dismutase-1 (SOD-1) cause amyotrophic lateral sclerosis (ALS). They were reproduced in SOD-1-G93A (SOD-1) and new FUS[1-359]-transgenic (FUS-tg) mice, where inflammation contributes to disease progression. The effects of standard disease therapy and anti-inflammatory treatments were investigated using these mutants.

Standardized human bone marrow-derived stem cells infusion improves survival and recovery in a rat model of spinal cord injury.

Spinal cord injury (SCI) is an incurable disorder with an unmet need of an effective treatment. Recently, autologous human bone marrow-derived stem cells have shown to promote functional improvement, due to their anti-inflammatory and regenerative/apocrine properties. In this study, the primary objective was to test whether a single intrathecal injection with a 100 μL suspension of 400,000 fresh human bone marrow-derived CD34 and an equal number of CD105 stem cells (Neuro-Cells (NC)), one day after balloon-compression of the spinal cord, improves motor function and reduces secondary damage in immunodeficient rats.

Stem cell grafting in parkinsonism--why, how and when.

Parkinson's disease is a devastating, progressive neurodegenerative disorder that affects the central and peripheral nervous systems. Although recent advancements have led to a better understanding of the disorder, there is currently no long-term disease-modifying strategy. Recently, preclinical data have identified the significant effects of pluripotent stem cell grafting in 6-OHDA and MPTP animal models of motor parkinsonism; there have also been some clinical data in patients with motor parkinsonism.

Cell based therapy in Parkinsonism.

Parkinson's disease (PD) is a synucleinopathy-induced chronic progressive neurodegenerative disorder, worldwide affecting about 5 million humans. As of yet, actual therapies are symptomatic, and neuroprotective strategies are an unmet need. Due to their capability to transdifferentiate, to immune modulate and to increase neuroplasticity by producing neurotrophic factors, adult stem cells (ASC) might fill this gap.

70th Birthday symposium of Prof. Dr. Riederer: autologous adult stem cells in ischemic and traumatic CNS disorders.

Ischemic and traumatic insults of the central nervous system both result in definite chronic disability, only to some extent responsive to rehabilitation. Recently, the application of autologous stem cells (fresh bone marrow-derived mononuclear cells including mesenchymal and hematopoietic stem cells) was suggested to provide a strategy to further improve neurological recovery in these disorders. During the acute phase, stem cells act mainly by neuroprotection with prevention of apoptosis, whereas during the chronic situation they provide neurorestoration by transdifferentiation and/or the secretion of neurotrophic factors.

Non-motor extranigral signs and symptoms in Parkinson's disease.

Clinical symptoms in Parkinson's disease (PD) comprise both motor and non-motor symptoms. In this disease, synucleinopathic-induced, nigral dopamine deficiency-related dysfunction of the basal ganglia is held responsible for the characteristic levodopa-responsive motor signs and symptoms (bradykinesia, hypokinesia, rigidity), known as parkinsonism and essential for clinical diagnosis in PD, as well as subtle motivational and cognitive dysfunctions. Some motor symptoms, such as tremor and postural instability, and most non-motor symptoms, however, are not fully levodopa-responsive, and suggested to manifest extranigral pathology.

Olfactory testing combined with dopamine transporter imaging as a method to detect prodromal Parkinson's disease.

Objective Olfactory dysfunction is an early and common symptom in Parkinson disease (PD). Previously, the authors demonstrated that idiopathic olfactory dysfunction in first-degree relatives of PD patients is associated with an increased risk of developing PD within 2 years. The aim of the present study was to determine the value of combined olfactory testing and SPECT scanning in predicting future PD in the same population of relatives over a 5-year period.

Frontal-striatal abnormalities underlying behaviours in the compulsive-impulsive spectrum.

In this paper, we tentatively bring together the psychiatric, neurological and addiction perspectives on the impulsive-compulsive spectrum of neuropsychiatric disorders, in order to understand the pathophysiology of impulse control disorders (ICDs) in Parkinson's disease. In an attempt to try to pool the various levels of information we will therefore focus on three disorders within the impulse-compulsive spectrum, i.e.

Cholinergic modulation of MEG resting-state oscillatory activity in Parkinson's disease related dementia.

Objective: EEG and MEG studies in Parkinson's disease (PD) related dementia (PDD) have shown a slowing of resting-state, oscillatory activity compared to non demented PD. Aim of the present MEG study was to determine whether treatment with the cholinesterase inhibitor rivastigmine would reverse this slowing of resting-state activity in PDD patients.

Methods: In eight PDD patients, whole head MEG was recorded in a resting-state condition before and after treatment with rivastigmine.

Hyposmia and executive dysfunction as predictors of future Parkinson's disease: a prospective study.

Olfactory deficits and executive dysfunction are early and common symptoms in Parkinson's disease (PD). Previous studies have shown that hyposmia can be a first sign of PD. The aim of the present study was to determine which of three olfactory tests and two selected tests of executive function would be the best predictor of future PD over a 5 year period.

Odor recognition memory is not independently impaired in Parkinson's disease.

The results of previous studies in small groups of Parkinson's disease (PD) patients are inconclusive with regard to the presence of an odor recognition memory impairment in PD. The aim of the present study was to investigate odor recognition memory in PD in a larger group of patients. Odor recognition memory and detection thresholds were assessed using components of the "Sniffin' Sticks" test battery in 55 non-demented PD patients (Hoehn and Yahr stages I-III) and 50 control subjects of comparable age and sex.

MEG resting state functional connectivity in Parkinson's disease related dementia.

Parkinson's disease (PD) related dementia (PDD) develops in up to 60% of patients, but the pathophysiology is far from being elucidated. Abnormalities of resting state functional connectivity have been reported in Alzheimer's disease (AD). The present study was performed to determine whether PDD is likewise characterized by changes in resting state functional connectivity.

Extended testing across, not within, tasks raises diagnostic accuracy of smell testing in Parkinson's disease.

The aim of this study was to determine whether extended olfactory testing within a single olfactory task and/or across olfactory tasks increases diagnostic accuracy of olfactory testing in Parkinson's disease (PD). Olfactory function was assessed using an extended version of the "Sniffin' Sticks", comprising 32-item odor identification and discrimination tasks, and a detection threshold task in 52 PD patients and 50 controls, all aged between 49 and 78 years. ROC curves based on sensitivity and specificity estimates were used to compare the diagnostic accuracy of extended and combined olfactory testing.

Parkinson's disease-related disorders in the impulsive-compulsive spectrum.

In Parkinson's disease (PD), there is increasing evidence for disorders in the impulsive-compulsive spectrum, related to the disease itself, to the pharmacological management of this disease or to both. These disorders comprise dopamine deficiency syndrome (with immediate reward seeking behaviour), dopamine dependency syndrome (with addictive behaviour), dopamine dysregulation syndrome (with both addictive behaviour and stereotyped behaviour) and impulse control disorders (such as pathological gambling, compulsive shopping, binge eating and hypersexuality). These disorders are especially seen in PD patients with young age of onset, higher doses of antiparkinsonian drugs, pre-existent or current depression, pre-existing recreational drug or alcohol use, and high novelty seeking personality traits.

Dopaminergic modulation of cortico-cortical functional connectivity in Parkinson's disease: an MEG study.

Recent studies have demonstrated increased resting-state cortico-cortical functional connectivity in untreated Parkinson's disease (PD). We set out to determine whether this connectivity can be modulated by dopamine replacement therapy (DRT) and explore the relationship of therapy-induced changes in connectivity with motor improvement in the relatively early stages of DRT in PD. Whole-head magnetoencephalography was performed in an eyes-closed resting-state condition in 37 patients with levodopa-treated PD (Hoehn and Yahr stages 1-3) both in a practically defined "OFF" and in the "ON" medication state.

Increased cortico-cortical functional connectivity in early-stage Parkinson's disease: an MEG study.

We set out to determine whether changes in resting-state cortico-cortical functional connectivity are a feature of early-stage Parkinson's disease (PD), explore how functional coupling might evolve over the course of the disease and establish its relationship with clinical deficits. Whole-head magnetoencephalography was performed in an eyes-closed resting-state condition in 70 PD patients with varying disease duration (including 18 recently diagnosed, drug-naive patients) in an "OFF" medication state and 21 controls. Neuropsychological testing was performed in all subjects.

Loss of thalamic serotonin transporters in early drug-naïve Parkinson's disease patients is associated with tremor: an [(123)I]beta-CIT SPECT study.

In vitro studies revealed serotonin transporter (5-HTT) decline in Parkinson's disease (PD). Yet, few studies investigated thalamic 5-HTT in vivo and its effect on PD heterogeneity. We analyzed thalamic [(123)I]beta-CIT binding (mainly reflecting 5-HTT binding) in 32 drug-naïve PD patients and 13 controls with SPECT.

Observations on the cortical silent period in Parkinson's disease.

Transcranial magnetic stimulation is a tool in the neurosciences to study motor functions and nervous disorders, amongst others. Single pulses of TMS applied over the primary motor cortex lead to a so-called cortical silent period in the recording from the corresponding muscle, i.e.