Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The evidence for supramedullary influences on cough is largely indirect. Cough can be voluntarily induced or inhibited, functions usually thought to reside in the cerebral cortex. A sensation of 'urge-to-cough' usually precedes cough due to an airway irritant stimulus, and this may well involve the cerebral cortex. In conditions with interruption of the pathways between the cortex and the brainstem, such as strokes and Parkinson's disease, voluntary cough may be inhibited without disruption of reflex cough from the larynx or lower airways. 'Habit cough', like Tourette's syndrome, is assumed to be cortically mediated. Placebos and many treatments based on complementary medicine are effective in inhibiting clinical cough, and the site of action is likely to be the cerebral cortex. In sleep and in anaesthesia cough is depressed and, again, this seems likely to be at a cortical level. However there are few or no experimental or clinical observation as to the localization and functions of supramedullary areas responsible for cough. It is a field of research wide open for exploration.
 ...
PMID:Supramedullary influences on cough. 1662 35

Rotenone and 1-methyl-4-phenyl pyridinium (MPP+) are two mitochondrial neurotoxins known to produce Parkinson's disease (PD) in experimental animals. In the present study, we compared drug-induced rotational asymmetry in rats lesioned using these neurotoxins at three distinct basal ganglia sites, the striatum, substantia nigra pars compacta (SNpc) and median forebrain bundle (MFB). The levels of dopamine (DA) in the ipsilateral striata of these hemiparkinsonian animals were assayed employing an HPLC-electrochemical procedure 2 days after the final rotational study. Rats infused with rotenone or MPP+ into the SNpc, but not into the striatum or MFB, exhibited contralateral rotations immediately after recovery from anesthesia. Irrespective of the lesion site or the toxin used, all the animals exhibited ipsilateral rotations when challenged with D-amphetamine. Apomorphine administration caused contralateral circling behavior in MFB-lesioned animals, but ipsilateral rotations in rats that received rotenone or MPP+ in the striatum or SNpc. Stereotaxic administration of rotenone into the MFB, SNpc or striatum caused a significant loss of DA in the ipsilateral striatum to varying degrees (96%, 62% and 30%, respectively, as compared to the contralateral side). However, unilateral MPP+ administration into the MFB, SNpc or striatum caused respectively about 98%, 74% and 59% loss of striatal DA. Behavioural observations and the neurochemical results indicate that, among the three anatomically distinct loci-lesioned, MFB-lesioned animals mimicked behavioral aberrations similar to nigral lesions caused by 6-hydroxydopamine, a classical parkinsonian neurotoxin. Moreover, the results point out that while both d-amphetamine and apomorphine-induced rotations could be considered as valuable behavioral indices to test novel drugs against PD, yet apomorphine-induced contralateral bias proves to be a more reliable indicator of specific destruction in the nigrostriatal pathway and development of post-synaptic DA receptor supersensitivity.
 ...
PMID:Rats with unilateral median forebrain bundle, but not striatal or nigral, lesions by the neurotoxins MPP+ or rotenone display differential sensitivity to amphetamine and apomorphine. 1682 Jan 97

The pedunculopontine nucleus (PPN) and the subthalamic nucleus (STN) are reciprocally connected by excitatory projections. In the 6-hydroxydopamine (6-OHDA) rat model the PPN was found to be hyperactive. Similarly, the STN and the substantia nigra pars reticulata (SNr) showed increased activity in Parkinson's disease (PD) animal models. A lesion of the STN was shown to restore increased activity levels in the SNr of 6-OHDA-treated rats. As the STN and the PPN were reciprocally connected by excitatory projections and both structures were shown to be hyperactive in PD animal models, the present study was performed in order to investigate the changes in neuronal activity of the STN and SNr under urethane anesthesia after unilateral ibotenic acid lesioning of the PPN in animals with previous unilateral 6-OHDA lesions of the substantia nigra pars compacta (SNc). The firing rate of STN neurons significantly increased from 10.3 +/- 0.6 spikes/s (mean +/- SEM) to 17.8 +/- 1.8 spikes/s after SNc lesion and returned to normal levels of 10.8 +/- 0.7 spikes/s after additional lesion of the PPN. Similarly, the firing rate of SNr neurons significantly increased from 19.0 +/- 1.1 to 25.9 +/- 1.4 spikes/s after SNc lesion, the hyperactivity being reversed after additional PPN lesion to 16.8 +/- 1.2 spikes/s. The reversal of STN and SNr hyperactivity of 6-OHDA-treated rats by additional PPN lesion suggests an important modulatory influence of the PPN on STN activity. Moreover, these findings could indicate a new therapeutic strategy in PD by interventional modulation of the PPN.
 ...
PMID:Lesion of the pedunculopontine nucleus reverses hyperactivity of the subthalamic nucleus and substantia nigra pars reticulata in a 6-hydroxydopamine rat model. 1704 96

We compared retrospectively the outcome of bilateral subthalamic nucleus (STN) stimulation in 15 patients with Parkinson's disease who underwent the procedure under general anesthesia (GA) with that achieved in 10 patients under local anesthesia (LA). At 3 months postoperatively, all cardinal parkinsonian motor symptoms, evaluated on Unified Parkinson's Disease Rating Scale were significantly improved compared to preoperative baselines in both groups. The administration of GA did not adversely affect postoperative improvements in motor and daily activity scores, except for off-medication bradykinesia. Our results suggest that GA compares favorably with LA in surgical procedure for bilateral STN stimulation.
 ...
PMID:Stereotactic surgery for subthalamic nucleus stimulation under general anesthesia: a retrospective evaluation of Japanese patients with Parkinson's disease. 1705 25

There is a great concern in the literature for the development of neuroprotectant drugs to treat Parkinson's disease. Since anesthetic drugs have hyperpolarizing properties, they can possibly act as neuroprotectants. In the present study, we have investigated the neuroprotective effect of a mixture of ketamine (85 mg/kg) and xylazine (3 mg/kg) (K/X) on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine (6-OHDA) rat models of Parkinson's disease. The bilateral infusion of MPTP (100 microg/side) or 6-OHDA (10 microg/side) into the substantia nigra pars compacta of adult male Wistar rats under thiopental anesthesia caused a modest (~67%) or severe (~91%) loss of tyrosine hydroxylase-immunostained cells, respectively. On the other hand, an apparent neuroprotective effect was observed when the rats were anesthetized with K/X, infused 5 min before surgery. This treatment caused loss of only 33% of the nigral tyrosine hydroxylase-immunostained cells due to the MPTP infusion and 51% due to the 6-OHDA infusion. This neuroprotective effect of K/X was also suggested by a less severe reduction of striatal dopamine levels in animals treated with these neurotoxins. In the working memory version of the Morris water maze task, both MPTP- and 6-OHDA-lesioned animals spent nearly 10 s longer to find the hidden platform in the groups where the neurotoxins were infused under thiopental anesthesia, compared to control animals. This amnestic effect was not observed in rats infused with the neurotoxins under K/X anesthesia. These results suggest that drugs with a pharmacological profile similar to that of K/X may be useful to delay the progression of Parkinson's disease.
 ...
PMID:Neuroprotective effect of ketamine/xylazine on two rat models of Parkinson's disease. 1722 1

The origin of changes in the neuronal activity of the globus pallidus (GP) and the subthalamic nucleus (STN) in animal models of Parkinson's disease (PD) is still controversial. The aim of the study was to investigate the neuronal activity of STN and GP neurons under urethane anesthesia in an early and in an advanced stage PD rat model. 6-Hydroxydopamine (6-OHDA) injection into the striatum induced a partial lesion of dopamine cells in the substantia nigra pars compacta (SNc) and fibers in the striatum. The GP firing rate decreased significantly with no significant change of the pattern. 6-OHDA injection into the SNc induced a total or subtotal lesion without any change in the firing rate and patterns of GP neurons. Concerning the STN, after partial lesion, the firing rate remained unchanged but the firing pattern significantly changed towards a more irregular and bursty pattern. In rats with total or subtotal lesion of the SNc the firing rate increased significantly and the relative amount of tonic neurons significantly decreased. Our results demonstrate that neuronal reactivity in the basal ganglia network considerably differs in the early versus late stage model of PD. We showed that the pathological activity of STN neurons after severe lesion is not mediated by the GP. Moreover, the unchanged activity of GP neurons is likely to be a consequence of the STN hyperactivity. These data suggest that in the GP-STN-GP network, the excitatory influence of the STN-GP pathway overrides that of the GABAergic GP-STN pathway, questioning the classical model of basal ganglia organization.
 ...
PMID:Effects of 6-hydroxydopamine-induced severe or partial lesion of the nigrostriatal pathway on the neuronal activity of pallido-subthalamic network in the rat. 1739 81

The consequences of short phases of restricted cerebral blood flow and iron enrichment of striatal tissues resulted in an animal model that could correspond to the basic features of a model for Parkinson's disease. An automatic and computerized hole-board offers simultaneous data on learning and cognitive memory capabilities, learning of distinct patterns of distributed food pellets found and eaten in a given time, switches between different locations of food in the holes and in different layout patterns. Wistar rats after 60 min of bilateral clamping of the carotid arteries (BCCA) under pentobarbital anesthesia received 1.5 microg FeCl3 injected one week after BCCA unilaterally into the ventrolateral striatum. The experiments showed that reduced cerebral blood flow and increased iron within the striatal tissue had the effect of retarding reactions. Rats after BCCA and iron need 180 s to find pellets deep inside holes that are distributed in a distinct pattern. During only 60 or 30s BCCA plus iron rats are no longer able to find the same number of pellets as over 180s. Rats after BCCA plus NaCl do not show such reduced success. These results point to the idea that cerebral oligemia and increased iron in the striatum stimulate the pathological symptoms of Parkinson's disease which need also more time to have reaction and success (see Fig. 5). The data covering abbreviated time-spans show how heavily the BCCA + Fe animals are dependent on longer times.
 ...
PMID:Cerebral oligemia and iron influence in cerebral structures--element of morbus parkinson models? 1744 32

The tricarboxylic acid cycle rate (Vtca) and the rate of glutamine synthesis (Vgln) in the pre- and post-MPTP-treated cynomolgus monkey (Macaca fascicularis) brain were measured non-invasively using a 2 Tesla 13C-magnetic resonance spectroscopy (13C-MRS; multislice 1H-13C correlation heteronuclear single quantum coherence spectroscopy) system. Before the infusion of 1-methyl-4-phenyl-1,2,3,6-tertahydropyridine (MPTP) into three monkeys, spectra were obtained by 13C-MRS from each monkey under anesthesia after the bolus injection of [1-13C] glucose (99% atom excess, 0.28 g/kg) followed by the continuous infusion of [1-13C] glucose (99% atom excess, 0.72 g/kg) into the saphenous vein for 3 h. The average values of Vtca were 0.475+/-0.077 (mean+/-S.D.) and 0.472+/-0.073 micromol/g/min, and the average values of Vgln were 0.042+/-0.007 and 0.041+/-0.008 mumol/g/min on the left and on the right hemisphere, respectively. Three monkeys were induced hemiparkinsonism by intracarotid (left) infusion of MPTP (0.6 mg/kg) and then were employed in 13C-MRS studies for 2 (5, 14 days), 3 (3, 8, 71 days) or 4 (5, 11, 27, 78 days) times, respectively, after the MPTP treatment. The average ratios of Vtca and Vgln on the left hemisphere to those on the right hemisphere in pre- and post-MPTP-treated monkeys were 0.837+/-0.085 and 1.373+/-0.132, respectively. These results of non-invasive 13C-MRS analysis of the MPTP primate model of Parkinson's disease indicate that the loss of the dopaminergic innervation from the caudate putamen may modulate the overall glucose metabolism to glutamate and glutamine in the ipsilateral cerebrum.
 ...
PMID:Changes in the rates of the tricarboxylic acid (TCA) cycle and glutamine synthesis in the monkey brain with hemiparkinsonism induced by intracarotid infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): studies by non-invasive 13C-magnetic resonance spectroscopy. 1791 69

Deep brain stimulation (DBS) is an effective treatment of Parkinson's disease (PD) for many patients. The most effective stimulation consists of high-frequency biphasic stimulation pulses around 130 Hz delivered between two active sites of an implanted depth electrode to the subthalamic nucleus (STN-DBS). Multiple studies have shown that a key effect of STN-DBS that correlates well with clinical outcome is the reduction of synchronous and oscillatory activity in cortical and basal ganglia networks. We hypothesized that antidromic cortical activation may provide an underlying mechanism responsible for this effect, because stimulation is usually performed in proximity to cortical efferent pathways. We show with intracellular cortical recordings in rats that STN-DBS did in fact lead to antidromic spiking of deep layer cortical neurons. Furthermore, antidromic spikes triggered a dampened oscillation of local field potentials in cortex with a resonant frequency around 120 Hz. The amplitude of antidromic activation was significantly correlated with an observed suppression of slow wave and beta band activity during STN-DBS. These findings were seen in ketamine-xylazine or isoflurane anesthesia in both normal and 6-hydroxydopamine (6-OHDA)-lesioned rats. Thus antidromic resonant activation of cortical microcircuits may make an important contribution toward counteracting the overly synchronous and oscillatory activity characteristic of cortical activity in PD.
 ...
PMID:Resonant antidromic cortical circuit activation as a consequence of high-frequency subthalamic deep-brain stimulation. 1792 54

A 68-year man with severe Parkinson's disease who had been implanted with deep brain stimulators into both sides, received an emergency surgery uneventfully under general anesthesia with standard monitoring. During the operation, the surgeon turned off the impulse generators and used bipolar diathermy. Postoperatively, he had transient episodes of severe Parkinson symptoms, which were controled by levodopa drugs.
 ...
PMID:[Anesthetic management of a patient with deep brain stimulators]. 1796 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>