Biomedical subjects

A Kaelin-Lang

Publications and source records attributed to A Kaelin-Lang.

16 recordsLinked to original sources

PubMed2007

[Surgery for Parkinson's disease].

Surgery for Parkinson's Disease (PD) is being increasingly used. The main reason for this renewal in surgical treatment for PD is the "deep brain stimulation" (DBS) that replaced the previously used stereotactic lesions in most centers. DBS allows a focal specific electrical stimulation of basal ganglia target instead of an irreversible lesion. Mainly bilateral DBS of the nucleus subthalamicus is now an established surgical treatment for PD. But DBS of the Globus pallidus internus and of the thalamus should still be considered in selected patients. DBS is an efficient treatment for motor complication of PD that can no longer be controlled by drug treatment. Dyskinesia, bradykinesia, tremor and rigor can be improved by DBS and the medication can be reduced. It is still unclear, however, how the improvement in motor symptoms affects quality of life in the long term. Furthermore, patients with severe cognitive and psychiatric symptoms as well as patients with severe axial symptoms should not be operated since these symptoms may worsen after surgery.

Deep Brain Stimulation↗

PubMed2005

Clinical and molecular genetic evaluation of patients with primary dystonia.

Primary dystonia is a movement disorder characterized by involuntary and sustained muscle contractions causing twisting or abnormal postures and mutations in several genes have been identified. Our goal was to investigate, whether the clinical presentation would differ between patients with a positive family history, and patients without. Furthermore, we have performed mutation analysis in the subgroup of patients with a positive family history. A total of 175 patients with primary dystonia were evaluated. Data on gender, presence and frequency of pain and tremor, age of onset, and the distribution of affected body parts were compared between patients with positive and negative family history. All exons of the torsion dystonia 1, GTP cyclohydrolase 1 and epsilon-sarcoglycan genes were examined in 40 patients by SSCP analysis of PCR products followed by sequencing of variant conformers. Dystonia patients with a positive family history of dystonia had an earlier age of onset and those with a positive family history of tremor more often associated tremor than those with a negative family history. Four new polymorphisms in the epsilon-sarcoglycan gene were found and others confirmed, but no known or new mutations could be detected. Our study supports the notion that primary dystonia is a genetically heterogeneous disease.

Adult↗

PubMed2003

The effect of transcranial magnetic stimulation on movement selection.

OBJECTIVE: To attempt to replicate previous findings that showed an influence of transcranial magnetic stimulation of the cortical motor areas on the selection of motor programmes on the contralateral side. METHODS: Healthy volunteers were asked to choose to make a right or left index finger extension movement freely after hearing the click produced by transcranial magnetic stimulation. The stimulation was applied to the motor areas (test), including the motor cortex, vertex, and prefrontal cortex, and in the air (control). RESULTS: There was no preference for choosing the hand contralateral to the stimulation site, in either test or control trials. CONCLUSIONS: Previous results could not be reproduced. Simple magnetic stimulation of the motor areas is insufficient to affect voluntary selection of movement.

Adult↗

PubMed2002

Accuracy of muscle localization without EMG: implications for treatment of limb dystonia.

Although botulinum toxin is an effective treatment for focal dystonia, the importance of electromyography (EMG) in identifying muscles and guiding injections is unclear. The authors examined the accuracy of muscle localization in 38 muscles in patients with focal hand dystonia without EMG guidance. Only 37% of needle placement attempts reached the target muscles or muscle fascicles. This study demonstrates that EMG guidance is needed for correct localization of desired muscles.

Animals↗

PubMed2002

Cholinergic influences on use-dependent plasticity.

Motor practice elicits use-dependent plasticity in humans as well as in animals. Given the influence of cholinergic neurotransmission on learning and memory processes, we evaluated the effects of scopolamine (a muscarinic receptor antagonist) on use-dependent plasticity and corticomotor excitability in a double-blind placebo-controlled randomized design study. Use-dependent plasticity was substantially attenuated by scopolamine in the absence of global changes in corticomotor excitability. These results identify a facilitatory role for cholinergic influences in use-dependent plasticity in the human motor system.

Administration, Cutaneous↗

PubMed2001

Effect of levetiracetam on human corticospinal excitability.

OBJECTIVE: To investigate whether levetiracetam (LTC) alters corticospinal excitability in humans. BACKGROUND: Although the antiepileptic activity of LTC is well recognized, its mechanism of action has yet to be determined. Transcranial magnetic stimulation (TMS) has been used to investigate the pharmacologic effects of various antiepileptic drugs on human corticospinal excitability. METHODS: The authors performed TMS before and after double-blind administration of 3000 mg LTC or placebo in six healthy volunteers. TMS measurements included resting and active motor threshold (MT), recruitment curve of motor-evoked potential amplitudes, intracortical inhibition, and facilitation using the paired-pulse technique and silent period. F-wave and compound muscle action potential (CMAP) were also measured. RESULTS: In recruitment curve measurements, motor-evoked potential amplitude was reduced for LTC with high stimulation intensity (130% and 140% of resting MT) compared with placebo (p < 0.05 and p < 0.01), but not with relatively low stimulation intensity (110% and 120%). The changes in other TMS measurements as well as F-wave and CMAP after LTC did not differ significantly from those observed after placebo administration. CONCLUSION: These results suggest that LTC reduces the corticospinal neuronal response to magnetic stimulation, preferentially affecting less excitable neurons. The lack of change in F-wave and CMAP suggests that this effect is mainly derived from the motor cortex.

Adult↗

PubMed2001

Transcranial magnetic stimulation in the rat.

Transcranial magnetic stimulation (TMS) allows for quantification of motor system excitability. While routinely used in humans, application in other species is rare and little is known about the characteristics of animal TMS. The unique features of TMS, i.e., predominantly interneuronal stimulation at low intensity and non-invasiveness, are particularly useful in evaluating injury and recovery in animal models. This study was conducted to characterize the rodent motor evoked potential to TMS (MEPTMS) and to develop a methodology for reproducible assessment of motor excitability in the rat. MEPTMS were compared with responses evoked by electrical stimulation of cervical spinal cord (MEPCES) and peripheral nerve. MEP were recorded by subcutaneous electrodes implanted bilaterally over the calf. Animals remained under propofol infusion and restrained in a stereotactic frame while TMS followed by CES measurements were obtained before and after 2 h of idle time. TMS was applied using a 5-cm-diameter figure-of-eight coil. MEPTMS had onset latencies of 6.7+/-1.3 ms. Latencies decreased with higher stimulation intensity (r=-0.7, P<0.05). Two morphologies, MEPTMS, 1 and MEPTMS, 2, were distinguished by latency of the first negative peak (N1), overall shape, and amplitude. MEPTMS, 2 were more frequent at higher stimulation intensity. While recruitment curves for MEPTMS, 1 followed a sigmoid course, no supramaximal response was reached for MEPTMS, 2. Mid-cervical spinal transection completely abolished any response to TMS. MEPCES showed a significantly shorter latency (5.29+/-0.24, P<0.0001). Two types of MEPCES resembling MEPTMS, 1 and 2 were observed. Neither MEPTMS nor MEPCES changed on repeat assessment after 2 h. This study demonstrates the feasibility and reproducibility of TMS in the rat. Sigmoid recruitment curves for MEPTMS, 1 suggest input-output properties similar to those of the human corticospinal system. Latency differences between CES and TMS point to a supraspinal origin of the MEPTMS. The two morphologies likely reflect different cortical or subcortical origins of MEPTMS.

Anesthetics↗

PubMed2000

Enhancing the quality of studies using transcranial magnetic and electrical stimulation with a new computer-controlled system.

Transcranial magnetic (TMS) and electrical (TES) stimulation of the human brain have become useful tools in neurophysiological and neuropsychological research. Here we describe an integrated system that allows experimental control, data recording and analysis of neurophysiological and neuropsychological TMS and TES procedures (including motor thresholds, recruitment curves, intracortical inhibition and facilitation with paired pulses). The system uses a multifunction input/output board and a set of virtual instruments (VI) programmed with the Labview graphical programming language. It also includes online curve fitting of recruitment curves using the Boltzmann sigmoid function and monitoring of the preinnervation grade of the target muscle. Modules for neuropsychological stimulus presentation or faster repetitive stimulation can be easily added. This system yields more accurate data recording and analysis in a user friendly and unified environment.

Computers↗

PubMed2000

Adenosine A2A receptor gene expression in the normal striatum and after 6-OH-dopamine lesion.

Adenosine A2A receptors are present on enkephalinergic medium sized striatal neurons in the rat and have an important function in the modulation of striatal output. In order to establish more accurately whether adenosine transmission is a generalized phenomenon in mammalian striatum we compared the A2A R expression in the mouse, rat, cat and human striatum. Secondly we compared the modulation of enkephalin gene expression and A2A receptor gene expression in rat striatal neurons after 6-OH-dopamine lesion of the substantia nigra. Hybridization histochemistry was performed with a 35S-labelled radioactive oligonucleotide probe. The results showed high expression of A2A adenosine receptor genes only in the medium-sized cells of the striatum in all examined species. In the rat striatum, expression of A2A receptors was not significantly altered after lesion of the dopaminergic pathways with 6-OH-dopamine even though enkephalin gene expression was up-regulated. The absence of a change in A2A receptor gene expression after 6-OH-dopamine treatment speaks against a dependency on dopaminergic innervation. The maintained inhibitory function of A2A R on motor activity in spite of dopamine depletion could be partly responsible for the depression of locomotor activity observed in basal ganglia disorders such as Parkinson's disease.

Aged↗

PubMed1999

Expression of adenosine A2a receptors gene in the olfactory bulb and spinal cord of rat and mouse.

The expression of adenosine A2a receptors (A2aR) in the mammalian striatum is well known. In contrast the exact distribution of A2aR in other regions of the central nervous system remains unclear. The aim of this study was to investigate the A2aR gene expression in the rat olfactory bulb and spinal cord, two regions which are seldom included in mapping studies. Secondly, we compared the A2aR expression in the rat and in the mouse brain. Hybridization histochemistry was performed with an S35-labelled radioactive oligonucleotide probe. The results show strong expression of A2aR in the mouse and rat striatum in accordance with previous reports. In the olfactory bulb a weak but specific expression of A2aR was found in the granular cell layer in both species. In contrast, no significant expression of the A2aR gene was observed in other parts of the brain or the rat spinal cord. The presence of the A2aR in the mammalian olfactory bulb suggests a functional role for this receptor in olfaction.

Animals↗

PubMed1999

Effects of adenosinergic agents on the vascular resistance and on the optic nerve response in the perfused cat eye.

The function of A1- and A2a-adenosine receptors in the control of vascular resistance and in the modulation of light-evoked neuronal activity was investigated in the isolated perfused cat eye. The A1 agonist CCPA, the A1 antagonist CPT, the A2a agonist CGS 21680 and the A2 antagonist DMPX were used. The agents were applied intra-arterially at concentrations in the low nanomolar to micromolar range during rod-selective photic stimulation. The flow rate of perfusate, reflecting vascular resistance and the light-evoked optic nerve response (ONR) were recorded. Our results show a vasodilating effect of both A1 and A2 agonists and a vasoconstricting effect of the respective antagonists. The dose-effect relationships are suggestive, however, of an A2a receptor-mediated mechanism. The amplitude of the ONR-ON component was decreased during application of both adenosine-agonists. Analysis of the dose-effect relationships and the blockade of the CCPA-induced decrease by CPT suggests that inhibition is mediated by A1 receptors. However, CGS 21680-mediated inhibition cannot be explained by unspecific binding at A1 receptors alone and suggests the involvement of inhibitory A2a receptors.

Adenosine↗

PubMed1998

Expression of adenosine A2a receptor gene in rat dorsal root and autonomic ganglia.

The adenosine A2a receptors (A2aR) play an important role in the purinergic mediated neuromodulation. The presence of A2aR in the brain is well established. In contrast, little is known about their expression in the periphery. The purpose of this study was to investigate the expression of A2aR gene in the autonomic (otic, sphenopalatine, ciliary, cervical superior ganglia and carotid body) and in the dorsal root ganglia of normal rat. Hybridization histochemistry with S35-labelled radioactive oligonucleotide probes was used. An expression of A2aR gene was found in the large neuronal cells of the rat dorsal root ganglia. The satellite cells showed no expression of A2aR gene. In the superior cervical ganglion, isolated ganglion cells expressed A2aR. In the carotid body clusters of cells with a strong A2aR gene expression were found. In contrast, the ciliary and otic ganglia did not expressed A2aR gene, and only few small sized A2aR expressing cells were demonstrated in the sphenopalatine ganglion. The discrete distribution of A2aR gene expression in the peripheral nervous system speaks for a role of this receptor in the purinergic modulation of sensory information as well as in the sympathetic nervous system.

Animals↗

PubMed1996

Cholinergic effects on cat retina In vitro: changes in rod- and cone-driven b-wave and optic nerve response.

To identify cholinergically mediated components in the optic nerve response (ONR) we studied effects of cholinergic agonists and antagonists in the arterially perfused cat eye. Acetylcholine, carbachol, scopolamine, quinuclidinylbenzilate and mecamylamine were applied intra-arterially in micromolar concentrations. Recordings of rod- and cone-driven ERG accompanied those of the ONR and revealed: (i) cholinergic agonists enhanced the b-wave, particularly under photopic conditions, whereas scopolamine decreased the b-wave. Mecamylamine induced biphasic effects (decrease followed by increase) in the amplitudes of the rod- and cone-driven b-waves. The effects on the cone-driven ERG were more marked than those on the rod-driven ERG. (ii) The ON-component of the ONR was increased, then decreased by acetylcholine. The cholinergic antagonists exerted complex changes in the ONR-ON component depending on dosage and adaptation. Scopolamine increased, then decreased the rod-driven ON-component, but mainly increased the cone-driven ON-component. Mecamylamine tended to increase the cone-driven, but to decrease the rod-driven ON-component of the ONR. (iii) The configuration of the rod- as well as for the cone-driven ONR, in particular the early plateau and OFF-components, were consistently and reversibly changed by cholinergic agonists, as well as by both muscarinic and nicotinic antagonists. Agonists decreased, and antagonists increased the amplitude of the plateau-component. We conclude that the ERG b-wave was enhanced by acetylcholine, but decreased by cholinergic antagonists. Cholinergic agonists and antagonists affect the same specific components of the ONR in a dose-related and reversible fashion, indicating a major contribution of cholinergic mechanisms to information processing in the cat retina.

Acetylcholine↗

PubMed1995

Effect of neurotropin on cerebral edema, calcium and other elements in mice subarachnoidally injected with carrageenan.

Neurotropin, an inhibitor of the kallikrein-kinin system, was therapeutically i.p. administered to mice with brain inflammation induced by subarachnoidal injection of carrageenan. Brain water content was determined by the wet/dry weight ratio. The concentrations of cerebral Ca, K, Mn, Fe, Cu, Zn, Se, Rb, and Sr were measured by particle-induced X-ray emission. It was found that neurotropin dose dependently reduced brain water content. The mean concentration of cerebral calcium was significantly lower in the neurotropin-treated group than that in the non-treated group, suggesting less cell damage. Since it has been reported that dexamethasone and some prostaglandin inhibitors have no effect on brain swelling in this model and that, in contrast to these drugs, neurotropin has only a weak inhibiting activity on carrageenan-induced paw swelling, it is hypothesized that the kallikrein-kinin system is differently implicated in cerebral and peripheral inflammation.

Analgesics↗

PubMed1995

[Binding and electrophysiology of the muscarinic antagonist QNB in the mammalian retina].

PURPOSE: Based upon the extensive information from various laboratories on cholinergic enzymes and receptors in mammalian retina as well as cholinergic effects on retinal neurons we became interested in studying (1) retinal binding of a muscarinic antagonist, Quinuclidinyl benzilate (QNB) and (2), effects of the antagonist on retinal information processing. METHODS: Eyes from deeply anesthetized cats were used for homogenate of freshly isolated retina in the binding study, or they were arterially perfused for electrophysiology in vitro. The electroretinogram (ERG) and the compound action potential of the optic nerve (optic nerve response, ONR) were recorded under rod- and cone-stimulating conditions. QNB was infused intraarterially for 10-30 min, followed by washout (avoiding recycling or extraocular metabolism). RESULTS: 3H-QNB revealed a high affinity to muscarinic receptors with a dissociation constant KD of 0.27 nM and a relatively high density of muscarinic binding sites of 110 fmol per mg protein. QNB enhanced the amplitude of the ERG b-wave, but decreased dose-dependently and reversibly the components of the ONR. In addition, we observed a moderate vasoconstriction as indicated by a slight, dose-related decrease in flow rate of perfusion. CONCLUSION: The biochemical data on binding of 3H-QNB in connection with the marked electrophysiological changes induced by QNB suggest a substantial contribution of muscarinic cholinergic transmission in the cat retina.

Animals↗

PubMed1995

[A PC program for evaluating electrophysiologic signals of mammalian eyes].

BACKGROUND: Electrophysiological measurements in the mammalian eye in vivo or in vitro, i.e. in the arterially perfused cat eye, require storage and analysis of a large amount of data: light-evoked signals, including the electroretinogram (ERG) and the optic nerve response (ONR) are stimulus-related and have to be measured in a triggered mode, whereas the DC-standing potential and flow rate of perfusion medium should be measured continuously. METHOD AND RESULT: In order to facilitate the analysis of these various signals, we developed a computer program, that allows an on-line data analysis and a trend indication for pharmacologically induced changes in signal size as well as efficient storage. The flexible system is based on a "labview" program, the application and efficiency of which are discussed.

Animals↗