Afferent and efferent connections of striatal grafts implanted into the ibotenic acid lesioned neostriatum in adult rats

Abstract

The afferent and efferent connections of grafts of fetal caudate-putamen, implanted into the ibotenic acid (IA)-lesioned striatum of adult rats, have been studied with wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP) as a combined retrograde and anterograde tracer, and with aldehyde fluorescence histochemistry for the visualisation of dopamine-containing nigrostriatal afferents from the host. The WGA-HRP was deposited in crystalline form (within a capillary tip) either into the depth of the graft tissue, or into the IA lesioned host striatum as a control. Labelling was only evaluated in specimens where the WGA-HRP deposit was entirely confined within the graft. Retrogradely labelled neurons were most consistently found in the ipsilateral host substantia nigra and the spared portions of the host CP, and in one case also in the midline and intralaminar thalamic nuclei normally projecting to the striatum. Some neurons, although weakly labelled, occurred in the deep layers of the frontal cortex in all grafted rats. Signs of anterograde WGA-HRP labelling in the host were found in one of the five animals in the ipsilateral globus pallidus and substantia nigra, pars reticulata. Fluorescence histochemistry revealed extensive ingrowth of dopamine-containing fibres from the host striatum into the grafted striatal tissue. The ingrowing fibres formed distinct and partly interconnected patches, most prominently in the peripheral regions of the grafts. The results provide evidence that intrastriatal grafts of fetal striatal tissue receive extensive dopaminergic afferents from the host substantia nigra, and that they may be capable of establishing connections also with thalamus, neocortex and globus pallidus of the host, as well as with the spared portions of the host caudate-putamen. The afferent connections from the thalamus and neocortex were notably more variable and sparse. However, since the control WGA-HRP deposits (into the lesioned host striatum) labelled the cortical and thalamic afferent neurons only poorly, it appears that the cortico-striatal and thalamo-striatal afferents (in contrast to the nigro-striatal ones) had undergone substantial degenerative changes (atrophy and/or cell death) in the long-term (6-11 months) IA-lesioned rats. The sparse thalamic and cortical afferent connections to the grafts may thus reflect an inability of the grafted striatal tissue to prevent the course of degenerative changes in these striatal input systems.

Transplanted fetal striatum in Huntington's disease: Phenotypic development and lack of pathology

“…In animal models, the proposed mechanisms of transplant-induced improvement observed include graft-derived transmitter release as well as the production of trophic factors (11,13,16,(43)(44)(45)(46). Previous animal studies have demonstrated reconnection of the cortical, thalamic and dopaminergic system with implanted fetal striatum (12,13,40,47). We demonstrate here that host neuronal systems that normally project to the striatum (for example dopaminergic neurons) can grow into the human striatal tissue grafts.…”

Neural transplants in patients with Huntington's disease undergo disease-like neuronal degeneration

“…Preclinical rodent and primate experiments demonstrated the feasibility of using embryonic striatal grafts for the treatment of HD. Fetal striatal grafts survive (5), induce behavioral recovery (6,7), and establish connectivity with the rodent brain (8,9). Similar results have been reported with xenografts of porcine and human striatal tissue into rodents (2,(9)(10)(11)(12).…”

Progressive Reparative Gliosis in Aged Hosts and Interferences with Neural Grafts in an Animal Model of Huntington's Disease

“…Groves et al, 2003) we were interested particularly in the development of the striatal neurotoxic lesion during a longer time frame. Surprisingly, the studies referring to long-term experiments are less frequent (Isacson et al, 1985;Pritzel et al, 1986;DiFiglia et al, 1988;Liu et al, 1990;Wictorin, 1992) and have not dealt with detailed histopathological characteristic of the progression of neurodegenerative process.…”