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Biomedical subjects

O Lindvall

Publications and source records attributed to O Lindvall.

At least 163 records · Page 9Linked to original sources
PubMed1987

Transplantation in Parkinson's disease: two cases of adrenal medullary grafts to the putamen.

Autologous adrenal medullary tissue was transplanted unilaterally to the putamen in two patients with severe Parkinson's disease. The first patient exhibited a transient, two-day improvement of motor performance in the limbs contralateral to the implantation site. He also had significantly longer episodes of normal function for about two months. The second patient reported a minor improvement of balance and gait, again lasting for two months. Electrophysiological studies of the motor readiness and auditory evoked potentials were consistent with increased catecholaminergic activity in the basal ganglia after transplantation in both patients. Positron emission tomography showed no postoperative alteration of receptor density in the putamen. No significant adverse effects of the transplantation were observed in the patients' performance on neurological and psychological tests or in their quantitative electroencephalogram and cerebral blood flow recordings. Immediately after the grafting, one patient showed transient signs of sympathetic hyperactivity, probably caused by release of catecholamines from the implanted tissue into the peripheral circulation. We conclude that catecholamine-rich cellular implants in the basal ganglia have transient beneficial effects in patients with severe Parkinson's disease.

Adrenal Medulla↗
PubMed1987

Grafted noradrenergic neurons suppress seizure development in kindling-induced epilepsy.

Norepinephrine-rich cell suspensions, prepared from the locus coeruleus region of rat fetuses, were grafted bilaterally into the hippocampus of rats made hypersensitive to hippocampal kindling by a neurotoxic lesion of the central catecholamine system. The animals with grafts showed a marked suppression of the onset and progression of kindling-induced epilepsy, and this effect was correlated with the degree of graft-derived noradrenergic innervation of the host hippocampal formation. We conclude that grafted neurons can modulate the excitability of epileptic brain regions.

Adrenergic Fibers↗
PubMed1986

Selective lesions of mesostriatal dopamine neurons ameliorate hypoglycemic damage in the caudate-putamen.

Unilateral 6-hydroxydopamine lesion of the mesostriatal dopaminergic system was found to ameliorate neuronal necrosis in the caudate-putamen following 30 min of insulin-induced hypoglycemic coma. We propose that increased release of dopamine in the striatum during hypoglycemia or in the recovery period potentiates a deleterious neuronal hyperexcitation, probably induced by excessive release of glutamate or related compounds, thereby aggravating neuronal necrosis.

Animals↗
PubMed1986

Mechanisms of epileptic brain damage: evidence for a protective role of the noradrenergic locus coeruleus system in the rat.

This study explores the possibility that the noradrenergic locus coeruleus system influences epileptic brain damage. Bilateral 6-hydroxydopamine lesions of the locus coeruleus projection to the forebrain were found to aggravate neuronal necrosis in the neocortex following 60 min of flurothyl-induced status epilepticus. We propose that the activation of the inhibitory locus coeruleus system during status epilepticus counteracts a deleterious neuronal hyperexcitation, probably induced by excessive release of excitatory amino acids, thereby limiting neuronal necrosis.

Adrenergic Fibers↗
PubMed1986

Short term status epilepticus in rats causes specific behavioral impairments related to substantia nigra necrosis.

Status epilepticus (SE) was induced for 40 min by flurothyl in well oxygenated rats. This insult resulted in selective destruction of up to 65% of the substantia nigra pars reticulata. We investigated the short and long term behavioral effects of this damage. No deficits were observed in sensorimotor reactivity, locomotor coordination, spontaneous or apomorphine-stimulated locomotor activity in the rats with induced epilepsy. However, these rats exhibited a long-lasting enhancement of amphetamine-stimulated locomotor activity. We propose that this selective impairment is caused by the necrosis of the pars reticulata. This damage might lead to deficient regulation either of mesostriatal dopamine neurons innervating nc. accumbens, or of neurons in the mesencephalic reticular formation mediating the locomotor response initiated in the nc. accumbens.

Animals↗
PubMed1986

Behavioural effects of human fetal dopamine neurons grafted in a rat model of Parkinson's disease.

The ventral mesencephalon, containing the developing dopaminergic neurons of the substantia nigra-ventral tegmental region, was obtained from aborted human fetuses of 9-19 weeks of gestation. The tissue was grafted into the striatum of rats previously subjected to a 6-hydroxydopamine lesion of the mesostriatal dopamine pathway. The graft recipients were immunosuppressed by daily injections of Cyclosporin A. Amphetamine-induced motor asymmetry was reduced, and finally totally reversed, only in rats receiving grafts from the 9-week old fetal donor. The fluorescence microscopic analysis revealed large numbers of surviving dopamine neurons, and extensive fiber outgrowth into the host striatum, in these rats. By contrast, rats receiving grafts from 11-19 week old donors had at most only few surviving dopamine neurons. These results indicate that human fetal mesencephalic tissue may be an efficient source of dopamine neurons for functional intracerebral grafting in patients with Parkinson's disease.

Animals↗
PubMed1985

Convulsive and non-convulsive ethanol withdrawal behaviour in rats with lesions of the noradrenergic locus coeruleus system.

The ascending noradrenergic pathways from the locus coeruleus were lesioned bilaterally in 10 rats by intracerebral 6-hydroxydopamine injections. Ten rats were sham-operated. All animals were subjected to a 4-day ethanol intoxication period using intragastric intubation. Intoxication and withdrawal assessments were performed blindly. The 6-hydroxydopamine lesions did not appear to affect tolerance to ethanol. During withdrawal, however, lesioned animals showed minor, but statistically significant changes in scores of certain non-convulsive withdrawal signs, but incidence and intensity of spontaneous and audiogenic convulsive seizures were not different between the groups.

Acoustic Stimulation↗
PubMed1985

Organization of diencephalic dopamine neurones projecting to the spinal cord in the rat.

Using the aluminium-formaldehyde method for visualization of catecholamines in combination with injections of the fluorescent retrograde tracer True Blue we have studied those diencephalic dopamine (DA)-containing cell groups which have been proposed to give rise to the DA innervation of the spinal cord and investigated the organization of the diencephalospinal DA system in detail. The A13 cell group was found to contain 370, and the A11 cell group 140, DA-producing cells on each side, whereas only very few such cells were found in the paraventricular hypothalamic nucleus. Tracer injections into the spinal cord labelled only DA cells within the A11 group. The overall majority of labelled cells were found ipsilaterally but some cells were also found contralaterally indicating the existence of a minor crossed dopaminergic projection to the spinal cord. Large tracer injections which covered the hemicord at different levels generally resulted in very similar distributions and numbers of retrogradely-labelled DA cells. The labelled DA-containing cells constituted 30-50% of the total number of labelled neurones in the ipsilateral A11 area and about 20-40% of the total number of DA containing cells in this area were labelled. Small injections that did not extend into the nucleus reticularis or the adjacent part of the lateral funiculus failed to label any diencephalic DA cells but usually labelled some non-DA cells in the A11 area. It is concluded that the diencephalospinal DA neurones have long axons that extend over several segments and possibly traverse the entire length of the spinal cord, giving off collateral branches at various levels. From the anatomical data of the present study and previous pharmacological and electrophysiological findings it seems possible that diencephalospinal DA neurones could modulate both sympathetic activity and nociception.

Animals↗
PubMed1985

Lesions of the locus coeruleus system aggravate ischemic damage in the rat brain.

The possibility that the noradrenergic locus coeruleus system influences brain damage following ischemia was explored in rats. Bilateral lesions of the locus coeruleus projections to the forebrain aggravated the neuronal necrosis in the hippocampal CA1 region and neocortex following complete cerebral ischemia induced by transient cardiac arrest. These findings provide evidence that the postischemic activation of the inhibitory locus coeruleus system could counteract a possible detrimental neuronal hyperexcitation, thereby limiting neuronal necrosis.

Animals↗
PubMed1985

Functional reactivation of the deafferented hippocampus by embryonic septal grafts as assessed by measurements of local glucose utilization.

Transection of the septo-hippocampal connections through fimbria-fornix damage in the rat results in profound hippocampal cholinergic deafferentation, and, when applied bilaterally, leads to severe and long-lasting impairments in learning and memory. Previous studies have shown that intrahippocampal septal grafts can reestablish a new cholinergic in the initially denervated hippocampal formation and at least partly compensate for the lesion-induced learning impairments in fimbria-fornix lesioned rats. The purpose of the present study was to determine the magnitude of lesion-induced alterations in cerebral function as reflected in local glucose use measured by (14C)-2-deoxyglucose (2-DG) autoradiography, and the degree to which this index of functional activity could be normalized following reinnervation from transplants of fetal cerebral tissue from the primordial septal region. Six months after unilateral fimbria-fornix transection the rate of glucose utilization was reduced markedly throughout the ipsilateral hippocampus when compared to the intact contralateral side, while in the neocortex only the cingulate cortex showed long-lasting reductions in glucose use. Rats that received a transplant of fetal septal-diagonal band tissue at the time of fimbria-fornix transection, and were sacrificed 6 months later, displayed significantly greater glucose utilization in the ipsilateral hippocampus and cingulate cortex than was measured in these areas in rats with lesion alone. The recovery in glucose use was paralleled by a significant increase in acetylcholinesterase (AChE) staining in several areas of the ipsilateral hippocampal formation and cingulate cortex. This index of graft-induced cholinergic reinnervation was, moreover, significantly correlated with the rate of glucose use. Thus, in the fimbria-fornix transected animals the magnitude of glucose depression correlated with the extent of reduction in AChE staining, and in the grafted animals the degree of normalization of glucose use was correlated with the graft-induced increase in AChE-staining density. These results thus indicate that the 2-DG autoradiographic technique can provide a unique opportunity to map both altered functional activity in localized areas of the brain following specific lesions and the extent to which transplant-derived reinnervation of the host may induce a return to normal functional levels in the target site.

Acetylcholinesterase↗
PubMed1985

Further studies on the use of the fluorescent retrograde tracer True Blue in combination with monoamine histochemistry.

Some basic methodological aspects on the use of the retrograde fluorescent tracer True Blue (TB) was studied in freeze-dried material in the rat CNS. On the basis of fluorescence morphology and intensity at different filter settings it was possible to objectively delineate 3 distinct zones of the TB injection site, and define degrees of retrograde labelling from the different zones. Correlative studies of injection sites in subportions of the spinal cord and retrograde labelling in cell bodies of defined nuclei in the brainstem and cortex showed that effective uptake occurred only from the central area of the injection (zone I), while the uptake from the less intensely fluorescent zone II was variable and could only be documented for systems terminating within this zone. Time-course studies revealed that the size of the injection site and the resulting retrograde labelling is stable up to at least two months after injection and that relatively long survival times are often needed for optimal labelling. For practical purposes a bulk transport velocity of 20 mm/day can be used for estimating the survival time required for reasonable retrograde labelling. The accumulation of TB did not interfere with the visualization of monoamines in the same neurones, and the tracer was never seen to be anterogradely or transcellularly transported.

Animals↗
PubMed1985

Evidence for amelioration of ischaemic neuronal damage in the hippocampal formation by lesions of the perforant path.

The effect of lesions of two excitatory afferent pathways on the cellular damage in the hippocampus following complete cerebral ischaemia was investigated in the rat. Lesions transecting the perforant path led to a significant decrease in cellular damage in the hippocampal CA1 region ipsilateral to the lesion as compared to the contalateral side and to control. Lesions of the fimbria-fornix, on the other hand, had no significant effects. We propose that the protective effect of the perforant path lesions is due to removal of glutamatergic/aspartergic pathways and that release of these excitatory amino acids might be a critical factor for neuronal necrosis following cerebral ischaemia.

Animals↗
PubMed1985

Cyclic AMP concentrations in rat neocortex and hippocampus during and following incomplete ischemia: effects of central noradrenergic neurons, prostaglandins, and adenosine.

The concentrations of cyclic AMP, noradrenaline, glycogen, glucose, lactate, pyruvate, labile phosphate compounds, and free fatty acids were investigated in the rat neocortex and hippocampus during and following cerebral ischemia. An incomplete ischemia of 5 and 15 min duration was induced by bilateral carotid clamping combined with hypotension. The postischemic events were studied after 5, 15, and 60 min of recirculation. Five minutes of ischemia did not significantly alter the neocortical or hippocampal concentrations of cyclic AMP. After 15 min of ischemia the neocortical levels decreased significantly below control values. In the recirculation period following ischemia a significant elevation of the cyclic AMP concentrations was observed. Following 5 min of recirculation after 5 min of ischemia the levels increased from 2.53 +/- 0.21 nmol X g-1 to 5.18 +/- 0.09 nmol X g-1 in the neocortex and from 2.14 +/- 0.16 nmol X g-1 to 3.52 +/- 0.35 nmol X g-1 in the hippocampus. Five minutes of recirculation following 15 min of ischemia led to a significant increase in the levels of cyclic AMP, to 12.86 +/- 1.43 nmol X g-1 in the neocortex to 5.58 +/- 0.57 nmol X g-1 in the hippocampus. With longer recirculation periods the cyclic AMP levels progressively decreased and were similar to control values after 60 min. Depletion of cortical noradrenaline by at least 95% was performed by injections of 6-hydroxydopamine into the ascending axon bundles from the locus ceruleus. The lesion did not significantly change the ischemic or post-ischemic neocortical and hippocampal levels of cyclic AMP, glycogen, or free fatty acids including arachidonic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗