Survival and growth of fetal catecholamine neurons transplanted into primate brain (original) (raw)

1986, Brain Research Bulletin

Dop~~~~ and norepinephrine neuroblasts of the ventral mesencephaion, hypothalamus, and dorsolaterai pons were transplanted from fetal African green monkeys into multiple brain sites in adult (host) African green monkeys. Tissue was grafted from both early and late gestational age fetuses. ~mmunohjstochemical analysis, with antibodies to tyrosine hydroxylase, a marker of Cat~hoIamine-containing neurons, showed large numbers of transpIanted cate~ho~am~ne neurons in host cerebral cortex, corpus striatum and lateral ventricles up to 69 days after tr~nspjantation. Serial reconstructions revealed extensive outgrowth of neuronal processes from large numbers of t~nspla~ted neurons as well as expansion of the size of t~osp~~ted (solid) grafts of fetal brain tissue in tbe host brain. Some g&s extended from the caudate nucleus into the adjacent lateral ventricles or from the cerebral cortex into the underlying corpus callosum and ven'tricle. There were dense networks of varicose fibers emanating from the tyrosine hydroxylase positive neurons within intrap~en~h~ma~ and intraventricular grafts. The size and shape of transplanted neurons retained characteristics common to catecholaminergic neurons fram the dissected regions of fetal brain. Thus, a variety of fetal, ~atechol~ine-cont~ning neurons survive t~nspiantat~on to primate brain and produce extensive neuritic outgrowths. Moreover, rejection of transplanted tissue was not apparent. These &dings provide essential information on nerve cell grafting in a species closely related to humans as a prerequisite in the consideration of neural transplants as therapeutic measures in neurological disease. Non-human primates Fetal catecholamine neurons Neural transplantation Parkinsonism

Catecholamine Fibers Form Synaptic Contacts with Hypothalamic Neurons Transplanted Adjacent to the Medial Forebrain Bundle in Rats

Annals of the New York Academy of Sciences, 1987

The establishment of connectivity between a host brain and a neural graft may be critical to the integration and ultimately the function of the transplanted tissue. It has been well established that neural grafts both receive afferent input from and project efferent fibers to the host.'-' Few s t u d i e~,~.~ however, have examined the issue of connectivity at the ultrastructural level to determine whether transplanted neurons, in fact, receive a relevant synaptic input from host fibers. We have addressed this problem using ultrastructural immunocytochemistry for tyrosine hydroxylase ( T H ) applied to fetal rat hypothalamic grafts that were transplanted adjacent to the medial forebrain bundle (MFB) of adult hosts. The grafted tissue, which contained the supraoptic and paraventricular nuclei as well as other portions of the medial basal hypothalamus, is normally richly innervated by noradrenergic fibers from the MFB.

Fetal mesencephalic neurons survive and extend long axons across peripheral nervous system grafts inserted into the adult rat striatum

Neuroscience Letters, 1984

In adult rats whose nigrostriatal dopamine (DA) pathway had been chemically damaged we implanted a fetal mesencephalic graft over the superior colliculus and joined it to the denervated striatum by means of an approximately 2 cm long segment of heterologous sciatic nerve. Monoaminergic neurons within the implant extended axons along the entire length of the nerve bridges and some of these fibers extended into the striatum, which is the normal target of nigral projections. Thus, combinations of fetal neuronal and peripheral nervous system grafts can be used in vivo to provide both a source and a substrate for lengthy axonal growth.

Monoaminergic reinnervation of the transected spinal cord by homologous fetal brain grafts

Brain Research, 1977

It was shown that immature noradrenaline (NA) containing cells from locus coeruleus and 5-hydroxytryptamine (5-HT) containing cells from the raph6 nuclei could survive homologous transplantation to adult spinal cords that were adrenergically denervated by a transverse lesion. Fully viable transplants were found at all postoperative times studied (0.5-4 months) and both NA and 5-HT cell bodies were found to produce a network of nerve terminals in the gray matter and axons in the white matter that reached cranially and caudally at least 10 mm from the cell bodies. The nerve fibers had a normal varicose appearance. It was concluded that NA and 5-HT axons can grow in adult lesioned white matter.

Fetal Neuronal Grafts in Monkeys Given Methylphenyltetrahydropyridine

The Lancet, 1986

Fetal substantia nigra cells of two different gestational ages were successfully transplanted into the brains of three methylphenyltetrahydropyridine-treated monkeys with severe parkinsonian motor and behavioural deficits. Functional improvement continued for 10 weeks after cell grafts into the striata of two monkeys with substantial numbers of tyrosine-hydroxylasepositive fetal neurons at necropsy. Behavioural improvement was correlated with increases in cerebrospinal fluid (CSF) homovanillic acid (HVA) concentrations after the transplants. A control monkey with inappropriately placed transplanted cells of an earlier gestational age remained severely parkinsonian and died during a similar period. CSF HVA fell slightly in this monkey from the low level seen before the transplants. Fetal dopamine neurons of two different gestational ages appear to survive transplantation in primates and have biochemical and functional effects.

Increased proportion of acetylcholinesterase-rich zones and improved morphological integration in host striatum of fetal grafts derived from the lateral but not the medial ganglionic eminence

Experimental Brain Research, 1993

Fetal striatal grafts are found to have a modular organization revealed by acetylcholinesterase (AChE) histochemistry. The AChE-rich zones represent the only portions of these grafts that are anatomically and functionally integrated into the host brain. In this study, the medial and lateral ganglionic eminences (MGEs and LGEs) were selectively dissected from the basal telencephalon of embryonic-day-14 (E14) rat fetuses to compare their relative contributions to the AChE-rich fraction of intrastriatal grafts. Separate cell suspensions prepared from either eminence were stereotaxically implanted into excitotoxically lesioned neostriatum of adult rats. Eight weeks after transplantation, grafts of the MGE were compared with those of the LGE with respect to the proportion of AChE-rich zones, graft size, graft morphology, and afferent dopaminergic innervation as revealed by tyrosine hydroxylase (TH) immunostaining. The mean AChE-rich fraction in LGE grafts (87%±4%) was markedly greater than the AChE-rich fraction in MGE grafts (25%±10%). The LGE grafts were also morphologically better incorporated into the lesioned host striatum, partially reconstituting the striatal morphology. There was no statistically significant difference in graft size between the two groups. The AChE-rich LGE grafts were TH immunoreactive, whereas the AChE-poor MGE grafts were not. We conclude that grafts derived exclusively from the fetal LGE reconstitute the striatal morphology and consist almost entirely of AChE-rich zones.

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