Publications by authors named "Michael Pirchl"

11 Publications

  • Page 1 of 1

Comparison of patient- and clinician-reported outcome measures in lower back rehabilitation: introducing a new integrated performance measure (t2D).

Qual Life Res 2021 Jun 15. Epub 2021 Jun 15.

Ludwig Boltzmann Institute for Rehabilitation Research, Reizenpfenninggasse 1, 1140, Vienna, Austria.

Purpose: Patient- and clinician-reported outcome measures (PROMs, CROMs) are used in rehabilitation to evaluate and track the patient's health status and recovery. However, controversy still exists regarding their relevance and validity when assessing a change in health status.

Methods: We retrospectively analyzed the changes in a CROM (Fingertip-To-Floor Test - FTF) and PROMs (ODI, HAQ-DI, NPRS, EQ5D) and the associations between these outcomes in 395 patients with lower back pain (57.2 ± 11.8 years, 49.1% female). We introduced a new way to measure and classify outcome performance using a distribution-based approach (t2D). Outcome measures were assessed at baseline and after 21 days of inpatient rehabilitation.

Results: Overall, the rehabilitation (Cohens d = 0.94) resulted in a large effect size outcome. Medium effect sizes were observed for FTF (d = 0.70) and PROMs (d > 0.50). Best performance rating was observed for pain (NPRS). We found that 13.9% of patients exhibited a deterioration in the PROMs, but only 2.3%, in the FTF. The correlation between the PROMs and FTF were low to moderate, with the highest identified for HAQ-DI (rho = 0.30-0.36); no significant correlations could be shown for changes. High consistency levels were observed among the performance scores (t2D) in 68.9% of the patients.

Conclusions: Different and complementary assessment modalities of PROMs and CROMs can be used as valuable tools in the clinical setting. Results from both types of measurements and individual performance assessments in patients provide a valid basis for the meaningful interpretation of the patients' health outcomes.

Trial Registration: This clinical study was entered retrospectively on August 14, 2020 into the German Clinical Trials Register (DRKS, registration number: DRKS00022854).
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http://dx.doi.org/10.1007/s11136-021-02905-2DOI Listing
June 2021

Ethanol transiently suppresses choline-acetyltransferase in basal nucleus of Meynert slices.

Brain Res 2012 Jun 20;1459:35-42. Epub 2012 Apr 20.

Laboratory of Psychiatry and Exp. Alzheimer's Research, Department of Psychiatry and Psychotherapy, Anichstr.35, 6020 Innsbruck, Austria.

The cholinergic system plays a major role in learning and cognition and cholinergic neurons appear to be particularly vulnerable to ethanol (EtOH) exposure. There are conflicting results if EtOH directly damages cholinergic neurons. Thus, the aims of the present study were (1) to investigate the effect of different EtOH concentrations on cholinergic neurons in organotypic brain slices of the nucleus basalis of Meynert (nbM) and (2) to study if the most potent cholinotrophic substance nerve growth factor (NGF) or inhibitors of mitogen activated kinase (MAPK) p38- and nitric-oxide synthase (NOS)-pathways may counteract any EtOH effect. Two-week old organotypic rat brain slices of the nbM were exposed to 1-100 mM EtOH for 7 days with or without drugs and the number of choline-acetyltransferase (ChAT)-positive neurons was counted. Our data show that EtOH significantly reduced the number of ChAT-positive neurons with the most potent effect at a concentration of 50 mM EtOH (54±5 neurons per slice, p<0.001), compared to control slices (120±13 neurons per slice). Inhibition of MAPK p38 (SB 203580, 10 μM) and NOS (L-thiocitrulline, 10 μM) counteracted the EtOH-induced decline of cholinergic neurons and NGF protected cholinergic neurons against the EtOH-induced effect. Withdrawal of EtOH resulted in a reversal of cholinergic neurons to nearly controls. In conclusion, EtOH caused a transient decline of cholinergic neurons, possibly involving MAPK p38- and NOS-pathways suggesting that EtOH does not induce direct cell death, but causes a transient downregulation of the cholinergic key enzyme, possibly reflecting a form of EtOH-associated plasticity.
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http://dx.doi.org/10.1016/j.brainres.2012.04.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370645PMC
June 2012

Homocysteine has anti-inflammatory properties in a hypercholesterolemic rat model in vivo.

Mol Cell Neurosci 2012 Apr 8;49(4):456-63. Epub 2012 Mar 8.

Laboratory of Psychiatry and Exp. Alzheimer's Research, Department of Psychiatry and Psychotherapy, Innsbruck Medical University, Austria.

Inflammation is a hallmark in many neurodegenerative diseases like Alzheimer's disease or vascular dementia. Cholesterol and homocysteine are both vascular risk factors which have been associated with dementia, inflammation and blood-brain barrier dysfunction. In previous studies we found that hypercholesterolemia but not hyperhomocysteinemia induced inflammation in rats in vivo. The aim of the present study was to investigate the effect of a combined treatment of Sprague Dawley rats with cholesterol and homocysteine for 5 months on spatial learning and memory, blood-brain barrier integrity and inflammation. Cholesterol treated rats showed severe learning deficits, while rats treated with cholesterol and homocysteine (Mix) counteracted the cholesterol-induced inflammation and partly the cortical blood-brain barrier disruptions, although cognition was still impaired. To study the potential protective effect of homocysteine, inflammation was induced in organotypic rat brain cortex slices and primary microglial cells by treatment with different inflammatory stimuli (e.g. lipopolysaccharide or tissue plasminogen activator). Tissue plasminogen activator-induced inflammation was counteracted by homocysteine. In conclusion, our data demonstrate that homocysteine significantly ameliorates cholesterol-induced inflammation and blood-brain barrier disruption but not the memory impairment, possibly involving a tissue plasminogen activator-related mechanism.
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http://dx.doi.org/10.1016/j.mcn.2012.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359503PMC
April 2012

Galactose counteracts hypoglycemia-induced decline of cholinergic neurons at low pH in organotypic rat brain slices of the basal nucleus of Meynert.

Pharmacology 2011 13;88(5-6):245-51. Epub 2011 Oct 13.

Laboratory of Psychiatry and Experimental Alzheimer's Research, Department of Psychiatry and Psychotherapy, Innsbruck Medical University, Innsbruck, Austria.

A growing body of evidence indicates that hypoglycemia and acidosis may contribute to the development of Alzheimer's disease (AD). The cell death of basal forebrain cholinergic neurons constitutes a hallmark of AD and directly correlates with cognitive impairment. The aim of the present study was to investigate, in an organotypic rat brain slice model of the basal nucleus of Meynert, the effects of glucose deprivation on cholinergic neurons under normal and acidic conditions. Furthermore, we were interested to explore whether different saccharides (galactose, fructose, saccharose, lactose) can replace glucose under low pH conditions. Our data show a pH-dependent survival of cholinergic neurons at a high (37.1 mmol/l) glucose level, which was markedly decreased at a low (5.6 mmol/l) glucose level. Galactose (+31.5 mmol/l) significantly counteracted the loss of choline acetyltransferase-positive neurons in low-glucose-treated slices, while fructose, lactose and saccharose only partly protected cholinergic neurons. In conclusion, our results indicate that replacement of glucose with different saccharides, but most potently with galactose, protects cholinergic neurons against hypoglycemia at a low pH.
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http://dx.doi.org/10.1159/000331861DOI Listing
April 2012

Differential effects of short- and long-term hyperhomocysteinaemia on cholinergic neurons, spatial memory and microbleedings in vivo in rats.

Eur J Neurosci 2010 Nov;32(9):1516-27

Laboratory of Psychiatry and Experimental Alzheimer’s Research, Department of Psychiatry and Psychotherapy, Innsbruck Medical, University, Anichstr. 35, A-6020 Innsbruck, Austria.

Hyperhomocysteinaemia (HHcy) has been identified as a cardiovascular risk factor for neurodegenerative brain diseases. The aim of the present study was to investigate the effects of short (5 months) or long (15 months) HHcy in Sprague–Dawley rats in vivo. Short- and long-term HHcy differentially affected spatial memory as tested in a partially baited eight-arm radial maze. HHcy significantly reduced the number of choline acetyltransferase (ChAT)-positive neurons in the basal nucleus of Meynert and ChAT-positive axons in the cortex only after short-term but not long-term treatment, while acetylcholine levels in the cortex were decreased at both time points. Nerve growth factor (NGF) was significantly enhanced in the cortex only after 15 months of HHcy. HHcy did not affect cortical levels of amyloid precursor protein, beta-amyloid(1-42), tau and phospho-tau181 and several inflammatory markers, as well as vascular RECA-1 and laminin density. However, HHcy induced cortical microbleedings, as illustrated by intensive anti-rat IgG-positive spots in the cortex. In order to study the regulation of the key enzyme ChAT, organotypic rat brain slices were incubated with homocysteine, which induced a decline of ChAT that was counteracted by NGF treatment. In conclusion, our data demonstrate that chronic short- and long-term HHcy differentially caused memory impairment, cholinergic dysfunction, NGF expression and vascular microbleedings.
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http://dx.doi.org/10.1111/j.1460-9568.2010.07434.xDOI Listing
November 2010

Hypercholesterolemia in rats impairs the cholinergic system and leads to memory deficits.

Mol Cell Neurosci 2010 Dec 6;45(4):408-17. Epub 2010 Aug 6.

Laboratory of Psychiatry and Exp Alzheimers Research, Department of Psychiatry and Psychotherapy, Innsbruck Medical University, Austria.

Alzheimer's disease (AD) is a chronic brain disorder characterized by cognitive impairment, cholinergic dysfunction, inflammation, tau and beta-amyloid pathology and vascular damage. Recent studies have shown, that high cholesterol levels are linked to the pathology of AD. The aim of our present work was to study the effects of hypercholesterolemia in adult rats. Five months after 5% cholesterol-enriched diet plasma cholesterol levels and total weight were significantly enhanced compared to controls. Spatial memory was studied in an 8-arm radial maze and cholesterol-treated rats showed an impaired learning and long-term memory. Hypercholesterolemia significantly reduced the number of cholinergic neurons in the basal nucleus of Meynert and decreased acetylcholine levels in the cortex. Nerve growth factor was only slightly enhanced in the cortex of cholesterol-treated animals. Levels of amyloid precursor protein, beta-amyloid(1-42), as well as tau and phospho-tau 181 were significantly enhanced in the cortex of cholesterol-fed rats. Hypercholesterolemia markedly increased several cerebral inflammatory markers and enhanced microglial CD11b-like immunoreactivity. Vascular density, stained by RECA-1 was not changed. However, cholesterol induced cortical microbleedings illustrated by intensive anti-rat IgG-positive spots in the cortex. In conclusion, our data demonstrate that hypercholesterolemia in rats caused memory impairment, cholinergic dysfunction, inflammation, enhanced cortical beta-amyloid and tau and microbleedings, all indications, which resemble an AD-like pathology.
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http://dx.doi.org/10.1016/j.mcn.2010.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2977849PMC
December 2010

Effects of cholesterol and its 24S-OH and 25-OH oxysterols on choline acetyltransferase-positive neurons in brain slices.

Pharmacology 2010 23;86(1):15-21. Epub 2010 Jun 23.

Laboratory of Psychiatry and Experimental Alzheimer's Research, Department of Psychiatry and Psychotherapy, Innsbruck Medical University, Innsbruck, Austria.

In Alzheimer's disease (AD) neurons expressing the enzyme choline acetyltransferase (ChAT) degenerate and a loss of cholinergic activity directly correlates with cognitive decline. Recent studies have suggested that cholesterol plays a role in AD. The aim of the present study was to explore if cholesterol and its oxysterols, 24S-hydroxycholesterol (24S-OH Chol) and 25-hydroxycholesterol (25-OH Chol), affect ChAT-positive neurons in organotypic brain slices of the basal nucleus of Meynert (nBM). We showed that slices expressed approximately 140 ChAT-positive neurons/slice after 2 weeks when incubated with nerve growth factor (NGF). This number markedly decreased when incubated without NGF to approximately 20 neurons/slice. Cholesterol and 24S-OH Chol delayed this decrease in ChAT-positive neurons. In contrast, 25-OH Chol induced a decline in ChAT-positive neurons in 2-week-old slices within 4 days. The effects of cholesterol and its oxysterols were exhibited in a dose- and time-dependent way. Our results show that cholesterol and 24S-OH Chol delays the decrease in ChAT-positive neurons, while 25-OH Chol rapidly decreases ChAT expression, suggesting differential mechanisms on ChAT expression in cholinergic nBM neurons.
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http://dx.doi.org/10.1159/000314333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4311142PMC
December 2010

S100b counteracts neurodegeneration of rat cholinergic neurons in brain slices after oxygen-glucose deprivation.

Cardiovasc Psychiatry Neurol 2010 24;2010:106123. Epub 2010 May 24.

Laboratory of Psychiatry and Exp. Alzheimer's Research, Department of Psychiatry and Psychotherapy, Innsbruck Medical University, Anichstra beta e 35, 6020 Innsbruck, Austria.

Alzheimer's disease is a severe chronic neurodegenerative disorder characterized by beta-amyloid plaques, tau pathology, cerebrovascular damage, inflammation, reactive gliosis, and cell death of cholinergic neurons. The aim of the present study is to test whether the glia-derived molecule S100b can counteract neurodegeneration of cholinergic neurons after oxygen-glucose deprivation (OGD) in organotypic brain slices of basal nucleus of Meynert. Our data showed that 3 days of OGD induced a marked decrease of cholinergic neurons (60% of control), which could be counteracted by 50 mug/mL recombinant S100b. The effect was dose and time dependent. Application of nerve growth factor or fibroblast growth factor-2 was less protective. C-fos-like immunoreactivity was enhanced 3 hours after OGD indicating metabolic stress. We conclude that S100b is a potent neuroprotective factor for cholinergic neurons during ischemic events.
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http://dx.doi.org/10.1155/2010/106123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875695PMC
July 2011

[Does acidosis in brain play a role in Alzheimer's disease?].

Neuropsychiatr 2009 ;23(3):187-92

Psychiatrisches Labor für Experimentelle Alzheimerforschung, Univ. Klinik für Allgemeine Psychiatrie und Sozialpsychiatrie, Medizinische Universität Innsbruck.

Alzheimer's disease is characterized by beta-amyloid plaques, tau pathology, cell death of cholinergic neurons, inflammatory processes and cerebrovascular damage. The reasons for the development of this chronic disease are not known yet. We hypothesize that chronic long lasting mild damage of the cerebrovascular brain capillaries cause hypoperfusion, acidosis and neurodegeneration, and induces a cell death cascade with beta-amyloid dysfunction and tau-pathology and inflammation. Vascular risk factors, such as hyperhomocysteinemia or hypercholesterolemia, may play a role in this process. The accumulation of chronic silent strokes may cause cognitive defects as seen in vascular dementia and Alzheimer's disease. This summary tries to link the different events, which occur in Alzheimer's disease, focusing on the cerebrovascular hypothesis.
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December 2009

Analysis of cerebrospinal fluid of Alzheimer patients. Biomarkers and toxic properties.

Pharmacology 2008 23;82(3):214-20. Epub 2008 Sep 23.

Department of General Psychiatry, Innsbruck Medical University, Innsbruck, Austria.

Alzheimer's disease (AD) is a severe, progressive and chronic disorder with strong cognitive deficits. Diagnosis of probable AD can be performed by measuring biomarkers in cerebrospinal fluid (CSF). The aim of the present study was to measure CSF levels of nerve growth factor (NGF), the anti-NGF auto-antibody, and the cholinesterases AChE and BChE, and to correlate them with beta-amyloid, tau and phospho-tau-181. We could show that NGF-like immunoreactivity, but not anti-NGF auto-antibody, was significantly enhanced in AD patients compared to healthy subjects, while both cholinesterases were not changed. beta-Amyloid(1-42) was decreased, while tau and phospho-tau-181 were increased. The commercial Promega NGF ELISA detected mature NGF but not wild-type-human-pro-NGF. Using a bioassay of brain slices, we showed that recombinant mature NGF enhanced survival of cholinergic neurons, while wild-type human pro-NGF displayed a less pronounced effect. The addition of CSF to brain slices exhibited strong toxic effects on the survival of cholinergic neurons. We conclude that in CSF of AD patients (at least partly) mature NGF-like immunoreactivity is enhanced, and is masked in a bioassay by the toxic properties of CSF.
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http://dx.doi.org/10.1159/000156487DOI Listing
January 2009

Effects of acidosis on brain capillary endothelial cells and cholinergic neurons: relevance to vascular dementia and Alzheimer's disease.

Neurol Res 2006 Sep;28(6):657-64

Laboratory of Experimental Alzheimer's Research, Department of General Psychiatry, Innsbruck Medical University, Austria.

Alzheimer's disease is a progressive brain disorder which is neuropathologically characterized by an increased number of beta-amyloid plaques, tau pathology and synapse loss. Recent research suggests that vascular pathology may be also important for the development and progression of Alzheimer's disease. It is still unknown whether there is a relation between damage of brain capillary endothelial cells (BCEC) and subsequent cholinergic cell death. The aim of this study was to examine the effects of acidosis on cell death of BCEC and cholinergic neurons in an organotypic brain slice model. We show that BCEC were heavily damaged in medium at pH<6.6. Cholinergic neurons incubated in medium pH 6.0 degenerated within 2-3 days and were not rescued by nerve growth factor (NGF). Lactate did not affect the survival of BCEC or cholinergic neurons. Both BCEC and cholinergic cells were not affected at pH 7.4, 7.0 or 6.6. It is concluded that both endothelial cells and cholinergic neurons have a high capacity to compensate for pH changes. At a certain pH, however, the vascular and neuronal cells show the same vulnerability, indicating that a low pH is deleterious for the cerebral microenvironment. Future studies are necessary to explore whether temporary pH changes could be responsible for cerebrovascular damage and cholinergic cell death. Acidosis may play an important role in the development of vascular dementia and Alzheimer's disease.
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http://dx.doi.org/10.1179/016164106X130371DOI Listing
September 2006