Biomedical subjects

F Block

Publications and source records attributed to F Block.

At least 91 records · Page 5Linked to original sources

PubMed1993

Quinolinic acid lesion of the striatum induces impairment in spatial learning and motor performance in rats.

Injection of quinolinic acid (QA) into the striatum of rats is known to produce neuropathological and neurochemical alterations similar to those observed in Huntington's disease (HD). One clinical feature of HD patients is cognitive impairment. Two weeks after stereotaxic injection of either QA (240 nmol) or solvent in rats spatial learning was tested in the Morris water maze. QA lesioned animals required more time to find the hidden platform. The swim speed was reduced in all trials compared to the controls. The swim distance itself was longer and the amount of swim distance along the side wall was significantly higher in QA lesioned rats. The present results suggest that QA lesion of the striatum leads to deficit in motor performance and in spatial learning.

Animals↗

PubMed1993

Remote microglial activation in the quinolinic acid model of Huntington's disease.

Intrastriatal injection of quinolinic acid (QA) in the rat leads to several structural and biochemical events which resemble neuropathological changes seen in the striatum of Huntington's disease patients. In the present experiment the accompanying microglial response in striatal projection areas following QA injection was studied immunocytochemically using monoclonal macrophage/microglial markers. After injection of 240 nmol of QA a marked microglial reaction was observed in the entire striatum, whereas injection of the same amount of solvent resulted only in a local microglial reaction around the injection site. Activated microglia were also found in the globus pallidus (GP), the entopeduncular nucleus (EP), the substantia nigra (SN), and the ventroanterior/ventrolateral, the ventromedial, and, in some rats, the reticular thalamic nucleus. The remote microglial reaction started in the first-order projection areas at Day 1 (GP) or Day 3 (EP, SN) and was found in the second-order projection areas (thalamic nuclei) by Day 5. Areas projecting to the striatum such as the amygdala and intralaminar thalamic nuclei remained free of activated microglia. It is concluded that a microglial response in striatal projection areas accompanies excitotoxic striatal injury. Anterograde degeneration of striatal projection neurons can explain the microglial activation in first-order projection areas but other mechanisms such as neuronal hyperexcitation following removal of inhibitory striatal input must be responsible for the rapid transsynaptic microglial activation seen in the thalamus.

Animals↗

PubMed1993

Effect of transient reduction of cerebral blood flow in normotensive rats on striatal dopamine-release.

Bilateral Clamping of both Carotid Arteries (BCCA) in normotensive rats is known to cause a transient reduction in cerebral blood flow. Using in vivo trans-striatal microdialysis and HPLC/ECD we measured the release of dopamine and DA-metabolites under these oligemic conditions. BCCA caused a substantial stimulation of striatal DA-release (40-fold) and a decrease of the outflow of DA-metabolites. The elevated DA-release returned to baseline levels before the onset of reperfusion. Upon reperfusion, DA-metabolites rose above their initial baseline values. Trans-striatal administration of glutamate-diethylester (GDEE, 10 mM) attenuated the oligemia-induced DA-release. A sudden reduction of blood flow appears to disrupt the compartmentation of dopamine in striatal dopaminergic nerve endings in a similar but more moderate manner as compared to ischemia.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

Functional studies on monoaminergic transmitter release in parkinsonism.

1. In vivo pulse voltammetry and apomorphine induced circling behaviour were used to study the effect of antiparkinsonian drugs and neurotoxins on striatal, extraneuronal dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations which are a measure of dopamine (DA) release/DA metabolism and serotonin (5-HT) release, respectively. 2. The DA precursor dihydroxyphenylalanine (DOPA, i.p.) increased extraneuronal DOPAC and reduced 5-HIAA levels whereas the opposite effect was induced by the 5-HT precursor 5-hydroxytryptophan (5-HTP, i.p.). Tryptophan, i.p., decreased the extraneuronal DOPAC levels without significant effect on 5-HT release. 3. The monoamine oxidase (MAO) inhibitors pargyline, i.p., and deprenyl, i.p., as well as the DA agonist apomorphine, i.p., decreased the catechol signal. The DA antagonist haloperidol, i.p., increased extraneuronal DOPAC. 4. In longterm studies unilateral application of the neurotoxins 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetra-hydroxypyridine (MPTP), and 1-methyl-4-phenylpyridinium cation (MPP+) into the substantia nigra pars compacta abolished the DOPAC signal in the striatum at the lesioned side. This effect can be partially or fully restored by DOPA depending on the time elapsed after neurotoxin administration. 5. In accordance with the voltammetric recorded unilateral lesion of the dopaminergic system the apomorphine stimulated circling behaviour was significantly enhanced in MPTP and MPP+ treated rats as compared with controls. 6. The results obtained indicate that antiparkisonian drugs and neurotoxins besides their effect on total catecholamine and 5-HT concentrations change specifically the extraneuronal levels of the transmitter (metabolites). Moreover the results suggest that neurotoxin-treated rats can be used as a model to study Parkinson-like effects with regard to the pathogenesis and treatment of this disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1993

Metabolic changes during and after transient clamping of carotid arteries in normotensive rats.

In the present experiments changes of local metabolism in the striatum, hippocampus, and frontal cortex during and after transient clamping of carotid arteries in normotensive rats (BCCA) were studied by continuous measurement of local cerebral temperature, partial oxygen tension (PO2), and extracellular levels of lactate. Local temperature in the striatum, hippocampus, and frontal cortex fell between 1.7 and 2.3 degrees C upon occlusion and quickly returned to preocclusion values after free flow had been established. Local PO2 was reduced in the striatum, hippocampus, and frontal cortex to values between 70 and 30% during BCCA. Immediately after termination of BCCA the PO2 showed a tendency to recover in the striatum and frontal cortex, whereas in the hippocampus, this process started later. Extracellular levels of lactate within these three structures increased during BCCA and went down to preocclusion values within the observed period of reperfusion. The results suggest that BCCA induces a transient anaerobic metabolism that seems to be sufficient to evoke functional changes without neuronal damage.

Animals↗

PubMed1993

Non-NMDA-mediated transmission of somatosensory-evoked potentials in the rat thalamus.

Somatosensory-evoked potentials (SEPs) were recorded from the somatosensory cortex of pentobarbital-anesthetized rats, in response to single electrical stimulation of the contralateral forelimb. The effects of microapplication of the selective N-methyl-D-aspartate (NMDA) antagonist, (-)-2-Amino-7-phosphonoheptanoate (AP7), and of the specific non-NMDA antagonist, 6,7-Dinitro-quinoxaline-2,3-dione (DNQX), in the ventrobasal thalamic nucleus on the amplitudes and latencies of cortical potentials were measured. The injection of DNQX resulted in a decrease in amplitude and an increase in the latency of cortical SEPs. These effects were a) dose dependent over the range 0.1 to 1.0 nmol, b) specific for non-NMDA receptors, and c) site specific. In contrast, microapplications of AP7 did not affect the SEPs. The present findings support the hypothesis that non-NMDA receptors in the ventrobasal thalamic nucleus are involved in the transmission of cortical SEPs.

Anesthesia↗

PubMed1993

N-methyl-D-aspartate (NMDA)-mediated muscle relaxant action of dextromethorphan in rats.

The present study examined whether the antitussive agent dextromethorphan, which is an antagonist at the N-methyl-D-aspartate (NMDA) receptor, depresses spinal reflexes in rats. Injection of both the specific NMDA antagonist (-)-2-amino-7-phosphonoheptanoate and of dextromethorphan dose-dependently reduced the magnitude of the polysynaptic flexor reflex without affecting the monosynaptic H-reflex. In contrast, the non-NMDA antagonist 6,7-dinitroquinoxaline-2,3-dione depressed the H-reflex in a dose-dependent manner without affecting the flexor reflex. The depressant effect of dextromethorphan on the flexor reflex was prevented by co-administration with NMDA but not with the non-NMDA agonist alpha-amino-3-hydroxy-5-terthyl-4-isoxazole-propionic acid. These data suggest that dextromethorphan exerts a muscle relaxant action via the NMDA receptor.

2-Amino-5-phosphonovalerate↗

PubMed1993

Levemopamil reduces spatial learning deficit following transient occlusion of common carotid arteries in normotensive rats.

The effect of the calcium channel blocker and 5-HT2 antagonist levemopamil on spatial learning impairment of rats subjected to transient bilateral clamping of carotid arteries (BCCA) was investigated. In addition, the acute effect of BCCA on local cerebral blood flow was measured in the presence and absence of levemopamil in a separate group of rats. Pretreatment with levemopamil prevented the BCCA-induced increase in escape latency during the test trials and ameliorated the BCCA-induced decrease in spatial bias during a probe trial. Under these experimental conditions, local cerebral blood flow fell to near ischaemic values in all mid- and forebrain regions during occlusion of the carotid arteries. However, pretreatment with levemopamil affected the BCCA-induced blood flow changes only in one brain area of 34 investigated. The present data suggest that pretreatment with levemopamil reduces impairment in spatial behaviour and that this effect seems not related to the compound's cerebral vasodilatory action, but to direct neuronal mechanisms.

Animals↗

PubMed1992

Retinal ischemia induced by occlusion of both common carotid arteries in rats as demonstrated by electroretinography.

In 2 models of reduced cerebral blood flow-permanent occlusion of the vertebral arteries plus transient occlusion of the common carotid arteries (4VO) and transient clamping of the common carotid arteries (BCCA)-the acute effects on the electrical function of the retina were monitored by recording the photopic electroretinogram. During both 4VO and BCCA the amplitude of the b-wave was reduced. Within 30 min of reperfusion after 4VO and after BCCA the b-wave had fully recovered. In contrast, the a-wave was not affected by either treatment. The data suggest that occlusion of common carotid arteries leads to retinal ischemia and might represent a useful model of amaurosis fugax.

Animals↗

PubMed1992

N-methyl-D-aspartate (NMDA)-mediated muscle relaxant action of memantine in rats.

The present study examined in vivo whether memantine exerts muscle relaxant activity via an antagonistic action at N-methyl-D-aspartate (NMDA) receptors. Intraperitoneal (i.p.) administration of memantine, 50-100 mumol/kg, reduced the tonic activity in the electromyogram recorded from the gastrocnemius muscle of spastic mutant rats. This effect was prevented by coadministration of NMDA. Memantine, while not affecting monosynaptic Hoffmann (H)-reflexes, depressed polysynaptic flexor reflexes in anaesthetized rats following i.p. (6.25-100 mumol/kg) or intrathecal (i.t., 10-500 nmol) administration. The latter effect was prevented by i.t. coadministration of NMDA, but not of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). These observations suggest that NMDA receptors might be involved in the mediation of the muscle relaxant activity of memantine.

Animals↗

PubMed1992

Abnormalities of somatosensory evoked potentials in the quinolinic acid model of Huntington's disease: evidence that basal ganglia modulate sensory cortical input.

Intrastriatal injection of quinolinic acid (QA) in rats provides an animal model that mimics some of the neuropathological and neurochemical alterations observed in the striatum of patients with Huntington's disease (HD). One of the very early neurophysiological signs in HD is a diminution of amplitude of early somatosensory evoked potentials (SEPs) recorded over the parietal cortex. The present study investigated whether the QA model exhibits similar neurophysiological abnormalities. Two weeks after unilateral intrastriatal injection of QA (240 nmol) or of the solvent, early SEPs were recorded with chronically implanted electrodes from the somatosensory cortex or from the ventrobasal nucleus of the thalamus of lightly pentobarbital-anesthetized rats, in response to single-shock electrical stimulation of the contralateral forepaw. Whereas intrastriatal injection of solvent did not influence SEPs, the striatal QA lesion significantly reduced the amplitude of early cortical SEPs by about 40% without affecting the latency. SEPs recorded from the ventrobasal nucleus were unchanged after QA lesion. Histological examination and glial fibrillary acid protein staining after intrastriatal injection of QA revealed no evidence for damage in the somatosensory system. It is concluded that (1) the QA animal model of HD mimics some of the SEP abnormalities of patients, and (2) a striatal lesion modulates somatosensory transmission to the cortex in rats.

Animals↗

PubMed1992

Transient reduction of cerebral blood flow leads to longlasting increase in GABA content in vulnerable structures and decreased susceptibility to bicuculline induced seizures.

Rats were exposed for 24 min to bilateral clamping of the common carotid arteries (BCCA) in pentobarbital anaesthesia. The GABA content was measured 24 hours, 48 hours, 4 days, 14 days and 3 months after BCCA. In other groups of rats seizures were elicited by i.p. injection of (+)-bicuculline (3 mg/kg) 24 hours, 48 hours, 4 days, 14 days and 3 months after BCCA. Analysis of the GABA content revealed significant increase compared with controls in the hippocampus, frontal cortex and substantia nigra from 24 hours up to 3 months. Bicuculline treatment induced tonic/clonic seizures and status epilepticus in sham operated animals; these effects were drastically diminished at various time points after BCCA. The present results suggest that BCCA produces a longlasting increase in GABA content and as a consequence protection from bicuculline-induced seizures.

Animals↗

PubMed1992

Behavioural effects after cholinergic stimulation of the reticular thalamic nucleus in rats.

This study investigated the functional relationship between the experimentally induced changes in the activity of the cholinergic, muscarinergic system of the rostral area of the nucleus reticularis thalami (TRN) and the motor behaviour. The effect of direct stimulation of the rostral TRN by the cholinergic agonist carbachol on the behaviour of freely moving rats was observed. Unilateral injection of carbachol (0.2-3.2 micrograms/0.5 microliters) into the rostral TRN caused catalepsy which appeared rapidly and was short-lasting. Furthermore, it induced impairment of the performance on the rota rod. Both effects were dose-dependent. The cholinergic antagonist scopolamine (6.66 micrograms) coadministered with the equimolar dose of carbachol (3.2 micrograms) antagonized the effects of carbachol on both behavioural tests. The described effects seem to be cholinergic- and site-specific within the rostral TRN. The present results suggest that activation of the cholinergic, muscarinergic receptors in the rostral TRN modulate the motor function of rats.

Animals↗

PubMed1991

Neuronal degeneration in hippocampus and cerebellum of mutant spastic Han-Wistar rats.

The neuropathology of the brain of mutant spastic Han-Wistar rats (Han-Wist SPA/SPA) was investigated using histological techniques. A surprising result was the detection of neuronal degeneration in the hippocampus and cerebellum of mutant spastic rat brains, whereas other regions, e.g. neocortex, isocortex, basal ganglia and thalamus, were overall normal. The CA3 sector in the septal third of the hippocampus including the cell band reaching into the hilus ('CA3c') showed a severe neuronal degeneration, whereas the granule cells of the dentate gyrus, several hilar neurons ('CA4') and the pyramidal cells in CA1 were found normal. In the cerebellum, a variable patchy degeneration of Purkinje cells was detected while the general layering was normal and granule cells and Golgi cells appeared preserved.

Animals↗

PubMed1991

Decreased susceptibility to seizures induced by bicuculline after transient bilateral clamping of the carotid arteries in rats.

Rats were exposed for 24 min to bilateral clamping of the common carotid arteries (BCCA) in pentobarbital anaesthesia. 14 days later the animals were subjected to subcutaneous injection of (+)-bicuculline (3 or 4 mg/kg). A significantly decreased susceptibility to bicuculline-induced seizures could be observed in BCCA treated rats compared with sham operated controls. It is suggested that BCCA treatment protects animals against status epilepticus and lethal toxicity produced by bicuculline. Electrographic recordings of the BCCA animals revealed no ictal activity within 1 h after bicuculline injection. An analysis of the GABA content showed a significant increase in the hippocampus (HPC), frontal cortex (FCX), parietal cortex and substantia nigra in BCCA animals compared with controls. It is therefore possible that an increase in GABA content postsynaptically counteracts the GABAA antagonistic effect of bicuculline in BCCA animals thus preventing the normal seizure inducing effect of this substance.

Animals↗

PubMed1991

Effects of bilateral clamping of carotid arteries on hippocampal kindling in rats.

Moderate reduction of cerebral blood flow by bilateral clamping of carotid arteries (BCCA) in pentobarbital anaesthetized Wistar rats induces decreased PO2 and temperature values in vulnerable brain structures such as hippocampus and frontal cortex during the acute phase of clamping. Up to two weeks chronic increased GABA contents in hippocampus, substantia nigra and frontal cortex could be observed. During this time the development of hippocampal kindling was difficult. These results demonstrated an acute and chronic influence of GABA on most vulnerable brain structures which, however, do not lead to ischemic impacts as histological analyses demonstrate.

Animals↗

PubMed1991

Reduction of ocular blood flow results in glial fibrillary acidic protein (GFAP) expression in rat retinal Müller cells.

Reduction of blood flow to the rat retina was achieved by either clamping both carotid arteries briefly (24 min) or combining clamping of the carotid arteries with permanent occlusion of the vertebral arteries. Analysis of retinas 6 days after operations showed that GFAP immunoreactivity is expressed throughout the retinal Müller cells, although this was variable in retinas from animals where only the carotid arteries were clamped. GFAP immunoreactivity was not associated with retinal Müller cells from control animals and no obvious neuronal damage was observed in retinas from operated animals. These data suggest that Müller-cell GFAP expression may be used as an index to follow possible processes leading to an ischemic insult.

Animals↗

PubMed1990

Spatial learning is affected by transient occlusion of common carotid arteries (2VO): comparison of behavioural and histopathological changes after '2VO' and 'four-vessel-occlusion' in rats.

Place learning in the Morris water maze following transient (24 min) occlusion of the common carotid arteries (2VO), and following permanent occlusion of both vertebral arteries plus transient (20 min) clamping of the carotids (4VO) was investigated in rats 6-9 days after occlusion. Both 2VO and 4VO treatment increased the latency to find the hidden platform during escape trials; spatial bias, tested in a probe trial, was decreased. Histological analysis revealed neural necrosis in the CA1 sector of the hippocampus in 4VO rats but not in 2VO animals. The data suggest that an experimentally induced reduction in cerebral blood flow of 50% (after 2VO) or 95% (after 4VO) produces persistent functional changes even in absence of actual neural damage.

Animals↗