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.

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.

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.

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.

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.

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.

Impairment of complex upper limb motor function in de novo Parkinson's disease.

The aim of the present study was to evaluate complex upper limb motor function in newly diagnosed, untreated Parkinson's disease (PD) patients. Four different unimanual upper limb motor tasks were applied to 13 newly diagnosed, untreated PD patients and 13 age- and sex-matched controls. In a handwriting task, PD patients had significantly reduced sentence length and writing velocity, and decreasing letter height in the course of writing.

Variability in the clinical expression of Parkinson's disease.

Parkinsonism is a clinical syndrome characterized by bradykinesia, hypo-/akinesia, muscular rigidity, and resting tremor, mainly caused by Parkinson's disease (PD). Symptoms of PD are due to a progressive loss of nigral neurons causing striatal dopaminergic denervation. However, nigral degeneration is only a part of the underlying synucleinopathy, and clinical symptoms go far beyond motor parkinsonism.

Abnormal susceptibility to distracters hinders perception in early stage Parkinson's disease: a controlled study.

Background: One of the perceptual abnormalities observed in Parkinson's disease (PD) is a deficit in the suppression of reflexive saccades that are automatically triggered by the onset of a peripheral target. Impairment of substantia nigra function is thought to lead to this reduced ability to suppress reflexive saccades.

Methods: The present study examined whether this perceptual deficit is also present in early stage PD when using hardly noticeable task-irrelevant stimuli.

Bimanual coordination dysfunction in early, untreated Parkinson's disease.

Bimanual coordination involves the simultaneous performance of either symmetrical (in-phase) or asymmetrical (anti-phase) movements with both hands and is known to be impaired in Parkinson's disease (PD). At present, it is unclear whether this aspect of motor function is already impaired in early stage, untreated PD patients. Therefore, we investigated the accuracy of bimanual coordination in 13 early stage, untreated PD patients and 13 age- and sex-matched healthy controls.

Enhanced sensitivity of dopaminergic neurons to rotenone-induced toxicity with aging.

Rotenone has been reported to induce various degrees of Parkinsonism in rats. We tested whether advancing age alters the sensitivity of dopaminergic neurons to rotenone. A low, systemic dose of rotenone had no effect on young rats, but led to a 20-30% reduction of tyrosine hydroxylase-positive neurons in the substantia nigra of older rats.

Idiopathic hyposmia as a preclinical sign of Parkinson's disease.

Olfactory dysfunction is an early and common symptom in Parkinson's disease (PD). In an effort to determine whether otherwise unexplained (idiopathic) olfactory dysfunction is associated with an increased risk of developing PD, we designed a prospective study in a cohort of 361 asymptomatic relatives (parents, siblings, or children) of PD patients. A combination of olfactory detection, identification, and discrimination tasks was used to select groups of hyposmic (n = 40) and normosmic (n = 38) individuals for a 2-year clinical follow-up evaluation and sequential single-photon emission computed tomography (SPECT), using [123I]beta-CIT as a dopamine transporter ligand, to assess nigrostriatal dopaminergic function at baseline and 2 years from baseline.