PubMed Health⌕ Search

Biomedical subjects

U Stenevi

Publications and source records attributed to U Stenevi.

At least 73 records · Page 4Linked to original sources
PubMed1983

Apomorphine-induced changes in local cerebral blood flow in normal rats and after lesions of the dopaminergic nigrostriatal bundle.

Systemic administration of the dopamine (DA) receptor agonist apomorphine leads to a general increase in cerebral blood flow (CBF) as determined by the autoradiographic iodoantipyrine technique. The magnitude of the increase varies between different regions but shows no obvious relation to the density of either DA terminals or receptors. The circulatory response is much more prominent in the lateral than in the medial caudate-putamen. Apomorphine seems to increase CBF both via a change in metabolic rate and via stimulation of dilatory vascular receptors. In animals with unilateral 6-hydroxydopamine lesions of the ascending DA pathways apomorphine induces an augmented CBF response in some denervated structures, notably caudate-putamen and globus pallidus. It is concluded that this is partly due to stimulation of denervated supersensitive vascular receptors, suggesting a direct dopaminergic control of the blood vessels in these areas.

Animals↗
PubMed1983

Nigral transplants reinnervating the dopamine-depleted neostriatum can sustain intracranial self-stimulation.

Transplants of embryonic substantia nigra reinnervated the striatum and were able to sustain intracranial self-stimulation in rats with brain lesions induced by 6-hydroxydopamine. Dopaminergic drugs and alterations in current intensity produced typical changes in response rates. Animals with electrodes implanted into cortical grafts or into the denervated striatum failed to exhibit self-stimulation. These findings suggest that transplanted dopamine neurons convey specific, temporally organized information axonally to the striatum.

Animals↗
PubMed1983

Reinnervation of the denervated adult spinal cord of rats by intraspinal transplants of embryonic brain stem neurons.

Previous studies have revealed a remarkable capacity of intracerebral grafts of embryonic brain tissue to establish extensive axonal connections with denervated areas in the brains of adult rats. In the present study we have explored the possibilities of using grafts in the spinal cord to substitute for the loss of noradrenergic brain-stem inputs to the severed spinal cord. Intraspinal grafts of embryonic pontine noradrenergic neurons were made into the lower thoracic region of adult rats. Three different surgical techniques were tested: (i) grafting to a small central cavity in the spinal-cord grey matter; (ii) grafting to a small subpial cavity involving removal of the dorsolateral third of the spinal-cord matter; (iii) grafting to the gap between the rostral and caudal stumps of the spinal cord after a nearly complete subpial transection. The results indicate that direct contact with the vessel-rich pia is essential for good survival of the grafts. Provided that the pia was left intact, the scarring around the grafts was minimal and the grafts fused well with both the grey and white matter of the cord. In the subpially transected cord, a brain-stem graft taken from a young embryonic donor fused well with both the rostral and the caudal stumps of the severed cord and thus restored tissue continuity across the gap. Large numbers of catecholamine (CA)-containing and non-monoaminergic cells were present in the transplants after 3-6 months. CA fluorescence histochemistry in combination with injections of fluorescent retrograde tracers revealed that both noradrenergic and non-monoaminergic neurons in the grafts had grown to reinnervate large segments of the host spinal cord. In those cases where the transplant had fused well with the cord, abundant CA-fluorescent axons could be traced across the graft-cord junction. They course along the grey and white matter of the host cord to reestablish a new CA terminal plexus in the grey matter as far as 12 mm from the graft.

Animals↗
PubMed1983

Intracerebral grafting of neuronal cell suspensions. III. Activity of intrastriatal nigral suspension implants as assessed by measurements of dopamine synthesis and metabolism.

The activity of intrastriatal grafts of nigral cell suspensions has been monitored biochemically, using radioenzymatic assays of dopamine, its major acidic metabolite, DOPAC, and DOPA accumulation after DOPA-decarboxylase inhibition. Implants of 4-9 microliter of nigral cell suspension restored striatal DA levels by an average of 13-18%, with the highest individual values reaching about 50% of control. DOPAC was restored from about 5% in the lesioned controls to about 20% of normal in the grafted animals. The DOPAC: DA ratios and the DOPA accumulation measures indicated that the grafted DA neurons were spontaneously active and that the transmitter turnover rate was on the average some 50-100% higher than the intact intrinsic nigrostriatal DA neurones. These results thus provide evidence that the intrastriatal nigral suspension grafts are capable of restoring dopaminergic neurotransmission in the previously denervated striatum.

Animals↗
PubMed1983

Intracerebral grafting of neuronal cell suspensions. IV. Behavioural recovery in rats with unilateral 6-OHDA lesions following implantation of nigral cell suspensions in different forebrain sites.

Single and multiple implants of nigral cell suspensions were grafted to the forebrains of rats with unilateral 6-hydroxydopamine-induced dopamine denervations. Control lesions alone induced a marked behavioural asymmetry, as assessed by amphetamine- and apomorphine-induced rotation, sensorimotor tests and side bias in an unbaited T-maze, and the animals were hyperactive to a low dose of apomorphine. Single suspension placements into different denervated striatal regions were capable of reversing the behavioural asymmetries dependent upon the specific placement for each test. Multiple suspension grafts were capable of reversing all behavioural asymmetries, and additionally abolished the supersensitive hyperactivity to apomorphine. By contrast, single suspension grafts placed into the substantia nigra or lateral hypothalamus had no detectable effect on any functional measure. The results indicate that nigral suspension grafts can be at least as effective as solid grafts in reversing the functional deficits induced by dopamine denervation, provided that placements are selected within appropriate dopamine terminal regions of the forebrain (e.g. caudate-putamen or nucleus accumbens).

Animals↗
PubMed1983

Intracerebral grafting of neuronal cell suspensions. V. Behavioural recovery in rats with bilateral 6-OHDA lesions following implantation of nigral cell suspensions.

Bilateral 6-hydroxydopamine-induced lesions of the ascending forebrain dopamine neurones induce a behavioural syndrome in rats which includes profound aphagia, adipsia, akinesia and bilateral sensorimotor neglect. Such animals will die unless maintained by intragastric feeding. Three experiments are reported in which we have attempted to ameliorate this syndrome with single or multiple placements of nigral cell suspensions into the forebrains of rats with bilateral dopamine depletions. Although the grafts were efficient in reversing the sensorimotor and akinetic impairments, and produced a significant increase in eating, the grafted rats remained hypophagic and adipsic. The results indicate that although many components of the bilateral dopamine denervation syndrome can be reversed by intrastriatal nigral suspension grafts, the severe eating and drinking deficits remain unameliorated.

Animals↗
PubMed1983

Intracerebral grafting of neuronal cell suspensions. VI. Survival and growth of intrahippocampal implants of septal cell suspensions.

The survival and growth of intrahippocampal septal suspension grafts were investigated by acetylcholine esterase (AChE) histochemistry in animals with lesions of the intrinsic septohippocampal cholinergic pathways. AChE was demonstrable in the grafts after the first postoperative week, and AChE-positive fibres were seen to extend into the host hippocampus by 3 weeks. Rapid fibre outgrowth occurred between 3 weeks and 3 months after grafting, and continued at a slower rate thereafter. By 6 months a fairly complete reinnervation of the initially denervated hippocampus was achieved in most specimens, and this persisted at 14 months, the longest postoperative time analysed. A comparison between the development of the AChE-positive neurones in the suspension grafts with that seen during ontogeny in situ suggested that the grafted neurones lagged behind normal development by at least 1 week. Similar to our previous observations on septal grafts implanted as solid tissue pieces, the pattern of the newly-formed AChE-positive innervation in the host hippocampal formation, established from the septal suspension grafts, was remarkably similar to that of the normal AChE-positive septal innervation. This pattern became established as soon as the graft-derived fibres first grew in, suggesting that the ingrowing axons extended and ramified preferentially into those hippocampal subfields which normally receive an AChE-positive innervation from the septal-diagonal band area.

Acetylcholinesterase↗
PubMed1983

Intracerebral grafting of neuronal cell suspensions. VII. Recovery of choline acetyltransferase activity and acetylcholine synthesis in the denervated hippocampus reinnervated by septal suspension implants.

The time-course and magnitude of fibre outgrowth from septal suspension grafts injected into the previously denervated hippocampal formation was monitored by measurements of choline acetyltransferase (ChAT), and the activity of the grafted neurons was assessed by measurements of [14C]acetylcholine (ACh) synthesis from [14C]glucose in vitro. Graft-derived ChAT activity was barely detectable 10 days after grafting, but increased sharply between 10 days and 1 month in the areas of the hippocampus located close to the septal implants. By 6 months ChAT activity was restored to near normal levels in all segments of the previously denervated hippocampus. The overall hippocampal [14C]ACh synthesis was also restored to normal levels in the grafted animals, and estimates of the ACh turnover rate suggested that the transmitter machinery of the newly established "septo-hippocampal" connections operated at a rate similar to that of the intrinsic septohippocampal pathway. The intrahippocampal septal suspension grafts, similar to the intrastriatal nigral grafts, thus seem to be capable of maintaining function at a relatively "physiological" level despite their abnormal positions.

Acetylcholine↗
PubMed1983

Intracerebral grafting of neuronal cell suspensions. VIII. Survival and growth of implants of nigral and septal cell suspensions in intact brains of aged rats.

Neuronal cell suspensions prepared from the ventral mesencephalon and the septal-diagonal band area of rat embryos were implanted into the depth of the intact neostriatum or hippocampus of 21-23 month old female rats. Graft survival, assessed 3-4 months after grafting, was comparable to that seen in our previous studies of young adult recipients. Fibre outgrowth into the host brain was evaluated in animals which were subjected to lesions of the intrinsic nigrostriatal or septohippocampal system 6-10 days before killing. Dense dopamine fibre outgrowth was seen within a zone of up to about 1 mm radius around the nigral implants, and dense growth of acetylcholine esterase (AChE) positive fibres occurred up to about 2 mm away from the septal implants. The overall magnitude of fibre outgrowth was less than that generally seen in previously denervated targets in young adult recipients, but it appeared to be as extensive as in young recipients when the grafts are placed in non-denervated targets. The distribution of the AChE-positive fibres from the septal implants in the host hippocampus suggested that the pattern found in the non-denervated target of the aged recipients was more diffuse, and partly different, from normal, and that age-dependent synapse loss in intrinsic connections may influence the patterning of the graft-derived innervation.

Acetylcholinesterase↗
PubMed1983

Intracerebral grafting of neuronal cell suspensions. II. Survival and growth of nigral cell suspensions implanted in different brain sites.

Dissociated dopamine-rich cell suspensions were prepared from the ventral mesencephalon of rat embryos and injected in one or several sites in striatal and non-striatal regions in the dopaminergically denervated brain of adult rats. While the grafts survived well in all sites, the dopamine fibre outgrowth was markedly different depending on whether the grafts occurred in an area normally innervated by the mesencephalic dopamine neurones (i.e. neostriatum or nc. accumbens) or in areas not normally innervated by these neurones (i.e. parietal cortex, lateral hypothalamus or substantia nigra). Moreover, in grafts placed at different sites along the trajectory of the nigrostriatal pathway the outgrowing fibres remained confined to the graft, and there was little evidence that the implanted neurones could elongate their axons along the pathway of the nigrostriatal tract to reach the striatum from a distance. Thus, the intracerebral suspension grafts provided efficient reinnervation of a denervated target only when placed in the immediate vicinity of the target area. The results of multiple graft placements indicate that a relatively complete restoration of a lost innervation should be possible to achieve in large areas of the brain, such as the striatal complex, with the suspension grafting technique.

Animals↗
PubMed1982

Septal transplants restore maze learning in rats with fornix-fimbria lesions.

In a study of the capacity of neural grafts to promote functional recovery in rats with fimbria-fornix lesions, 5 groups of rats were studied behaviourally and with acetylcholinesterase (AChE) histochemistry: (1) sham-operated controls; (2) bilateral fimbria-fornix lesions; (3) bilateral lesions plus bilateral solid embryonic septal grafts to the lesion cavity; (4) bilateral lesions plus bilateral embryonic septal suspension injections into the hippocampus; and (5) bilateral lesions plus bilateral solid embryonic locus coeruleus grafts to the lesion cavity. Seven months were allowed for growth of the grafts and reinnervation of the host hippocampus prior to behavioural testing. The control rats were able to rapidly learn a rewarded alternation task, while the performance of animals with bilateral fimbria-fornix lesions alone remained at a chance level. Both types of septal grafts (rich in cholinergic neurones) but not the locus coeruleus grafts (rich in noradrenergic neurones) reversed the impairment. Behavioural recovery correlated significantly with AChE-positive fibre ingrowth from the grafts into the denervated host hippocampus. However, the septal grafts did not ameliorate the lesion-induced disturbances in spontaneous activity or spontaneous alternation. Thus, the observed behavioural recovery appears specific to the conditioned alternation task and dependent upon cholinergic reinnervation of the hippocampus.

Acetylcholinesterase↗
PubMed1982

A model for xenotransplantation of human malignant astrocytomas into the brain of normal adult rats.

Transplantation of human brain tumours into the brain of normal laboratory animals is still considered to be unsatisfactory by many researchers, despite the fact that the brain is considered an immunologically privileged site. We present in this paper a model of xenotransplantation fo human astrocytomas grade III-IV into the brain of normal, adult Sprague-Dawley rats with good take rates, i.e. takes in two thirds of the animals, half of these with large, infiltrating tumours. The transplants are placed using a microsurgical technique in the vessel-rich choroidal fissure in the host brain from where rapid vascularization occurs. The technique has previously been used for CNS-regeneration studies. This model should provide an excellent opportunity to study human malignant astrocytomas in a milieu as natural as possible.

Animals↗