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Biomedical subjects

U Stenevi

Publications and source records attributed to U Stenevi.

At least 109 records · Page 6Linked to original sources

Functional reinnervation of rat hippocampus by locus coeruleus implants.

Transplants of the embryonic locus coeruleus (LC) region were implanted into the circuity of the hippocampal formation in adult rats in which the normal adrenergic afferents to the hippocampus had been removed. The growth of new adrenergic axons from the implant in the denervated hippocampus was followed for 1-14 months after surgery by means of fluorescence histochemistry, and the function of the implant-hippocampal connections was tested electrophysiologically after 2-3 months survival. In the successful cases the entire hippocampal formation was reinnervated from the LC implant within 3-6 months after operation, and the newly formed innervation still persisted unchanged by 14 months. The reinnervation was equally effective irrespective of the route by which the axons entered the hippocampus, i.e. along the lesioned fornix-fimbria or along a retrosplenial route. The pattern formed by the ingrowing LC axons mimicked to a large extent that of the normal LC afferents. Little growth was seen into denervated terminal fields of the commissural, septal or entorhinal afferents, pointing to a preference of the ingrowing LC fibers for the areas normally innervated by adrenergic afferents. In the electrophysiological experiments, stimulation of the LC implants caused (in 20 out of 29 cells monitored) an inhibition of the spontaneous activity of neurons in the host hippocampus. This inhibition had a relatively long latency and a long duration, similar to that observed after stimulation of the innate LC in the intact rat. As in the normal rat, the inhibitory responses were blocked by systemic or local application of the beta-adrenergic receptor blockers propranolol or sotalol. It is concluded that the adult rat brain is capable of carrying out all steps involved in correct functional reinnervation of a denervated region. Moreover, the implant-hippocampal preparation should be a highly suitable model system for functional studies of a central noradrenergic connection.

Adrenergic Fibers↗

Intracephalic implants: a technique for studying neuronal interactions.

Implants of embryonic neural tissue from all regions of the neuraxis survive grafting to the brains of adult rats. After implantation, neurogenesis and differentiation continue, and connections are formed with the mature host brain. Thus, the intracephalic implants provide excellent model systems for studying cellular interactions that regulate synaptogenesis and determine the cytoarchitectonic organization of developing neural tissues.

Animals↗

Dopamine and noradrenaline neurons projecting to the septal area in the rat.

The organisation of the catecholamine innervation of the rat spetal area was investigated by means of the glyoxylic acid fluorescence method in combination with dopamine uptake studies, lesions and retrograde tracing of horseradish peroxidase. The following catecholamine systems to the septum could be established: 1. The Locus Coreuleus Noradrenergic System. These axons are widespread in the septum forming a moderately dense innervation in the anterior hippocampus, the medial septal nucleus, the nucleus of the diagonal band, and the interstitial nucleus of the stria terminalis, and a sparse innervation in the lateral septal nucleus and the septofimbrial nucleus. 2. The Medulla Oblongata Noradrenergic System. This system originates in the A1, A2 or A3 cell groups, the axons forming a very dense innervation in the ventral part of the interstitial nucleus of the stria terminalis, a moderately dense innervation in the nucleus of the diagonal band and lateral septal nucleus, and a sparse innervation in the medial septal nucleus, the septofimbrial nucleus and the dorsal part of the interstitial nucleus of the stria terminalis. 3. The Mesencephalic Dopaminergic System. This system originates in the medial part of the A10 cell group, the axons forming two distinct terminal patterns. In the first type, smooth axons form pericellular arrangements around non-fluorscent neurons in the lateral septal nucleus. The second type is formed by fine-varicose axons which form a dense band around the fornix in the medial part of the lateral septal nucleus. 4. The Incerto-Hypothalamic Dopaminergic System. These axons most probably originate in cell bodies of the diencephalic A11, A13 and A14 cell groups, and are found in the lateral septal nucleus at the level of the anterior commissure.

Animals↗

Transplantation of central and peripheral monoamine neurons to the adult rat brain: techniques and conditions for survival.

The conditions for survival of transplants of peripheral and central monoamine neurons in the adult rat brain were studied using fluorescence histochemistry. Pieces of the superior cervical ganglion from newborn and adult rats and CNS tissue containing noradrenaline (NA), dopamine (DA) and indolamine (IA) neurons from embryonic, newborn and adult rats were transplanted to various brain sites using different techniques: insertion of the graft by means of a glass rod, by "injection", or by direct implantation of the graft in a resection cavity. Three principally different locations for the graft were tested: within the brain parenchyma in the caudal diencephalon and the caudate nucleus; onto the dorsal surface of the caudate nucleus; and onto the pial covering in the choroidal fissure after removal of the overlying cortex and parts of the hippocampal formation. Attempts were also made to transplant to the dorsal surface of the caudate nucleus or the hippocampus with the aid of an "artificial" vascular bed, achieved by previous transplantation of an iris. Consistent survival of the transplanted central and peripheral neurons was obtained only when the transplant was placed in contact with a vessel-rich tissue, such as the pia in the choroidal fissure or the "artificial" vascular bed. While the majority of the monoamine-containing neurons in the transplants died within the first month after transplantation, a significant number of neurons (up to about 150 in the ganglionic pieces and up to about 500 in the embryonic or newborn CNS pieces) survived for at least half a year in the brain. Survival of transplanted adult central monoamine neurons was not observed. A substantial outgrowth of axons was observed from all types of neurons in their new location. These newly formed fibers formed extensive fiber patterns within the transplant itself, around pia vessels, and within the adjacent brain tissue, above all in the hippocampal formation. The usefulness of the present transplantation technique for the exploration of mechanisms underlying reformation of axonal connections in the adult mammalian CNS is discussed.

Age Factors↗

Regeneration of central cholinergic neurones in the adult rat brain.

The regrowth of lesioned central acetylcholinesterase (AChE)-positive axons in the adult rat was studied in irides implanted to two different brain sites: in the caudal diencephalon and hippocampus, and in the hippocampal fimbria. At both implantation sites the cholinergic septo-hippocampal pathways were transected. At 2-4 weeks after lesion, newly formed, probably sprouting fibres could be followed in abundance from the lesioned proximal axon stumps into the iris transplant. Growth of newly formed AChE-positive fibres into the transplant was also observed from lesioned axons in the anterior thalamus, and to a minor extent also from the dorsal and ventral tegmental AChE-positive pathways and the habenulo-interpeduncular tract. The regrowth process of the sprouting AChE-positive, presumed cholinergic fibres into the iris target was studied in further detail in whole-mount preparations of the transplants. For this purpose the irides were removed from the brain, unfolded, spread out on microscope slides, and then stained for AChE. During the first 2-4 weeks after transplantation the sprouting central fibres grew out over large areas of the iris. The new fibres branched profusely into a terminal plexus that covered maximally about half of the iris surface, and in some areas the patterning of the regenerated central fibres mimicked closely that of the normal autonomic cholinergic innervation of the iris. In one series of experiments the AChE-staining was combined with fluorescence histochemical visualization of regenerated adrenergic fibres in the same specimens. In many areas there was a striking congruence in the distributional patterns of the regenerated central cholinergic and adrenergic fibres in the transplant. This indicates that - as in the normal iris - the sprouting cholinergic axons (primarily originating in the lesioned septo-hippocampal pathways) and adrenergic axons (primarily originating in the lesioned axons of the locus neurones) regenerate together along the deneravated Schwann cell sheaths. From a comparison between the central reinnervation process and the process of reinnervation of the iris by peripheral cholinergic axons after transplantation to the anterior eye chamber, it is concluded that the regenerative capacity of central cholinergic neurones (above all the septo-hippocampal system) is not much inferior to that of their peripheral counterparts when given similar growth conditions. Moreover, central cholinergic neurones seem partly able to replace the peripheral ones in the reinnervation of a denervated peripheral target.

Acetylcholinesterase↗