An Evaluation of the Possible Protective Effects of Neonatal Striatal Transplants Against Kainic Acid-Induced Lesions

The present study examined the recent report that transplantation of neonatal striatal tissue into kainic acid (KA) lesioned striatum protected the contralateral striatum from a subsequent KA lesion. We did not find a significant difference in the survival rate of animals that received neonatal striatal transplants into a KA lesioned striatum followed by a subsequent lesion of the contralateral striatum compared to those animals that received bilateral KA-induced striatal lesions alone. The tissue transplants did not protect against the degeneration of striatal neurons induced by KA. Indeed, the survival rate was very low (25%) in the transplant groups. A second experiment was also performed to examine whether a neonatal striatal transplant might reduce the severe syndrome of aphagia and adipsia associated with KA lesions of the striatum. Animals that received the neonatal striatal transplants showed increased aphagia and adipsia compared to animals only receiving the KA lesion. Again, the transplant group had a very low survival rate (10%). The present study was unable to confirm that neonatal striatal transplants protect against KA lesions either by themselves or in conjunction with a recent KA lesion.

Fetal Transplant-Induced Restoration of Spatial Memory in Rats with Lesions of the Nucleus Basalis of Meynert

Bilateral lesions of the nucleus basalis of Meynert (nbM) in rats produced mnemonic deficits when subjects were tested on tests of spatial memory over a period of 3 to 7.5 months postoperatively. The transplantation of cholinergic-rich, fetal ventral forebrain tissue to either two or four frontoparietal cortical sites normalized performance on the spatial memory tasks. However, which transplant condition yielded recovery depended upon the nature of the task and/or posttransplantation interval. When assessed 8 months following transplant surgery, cortical choline acetyltransferase and acetylcholinesterase activity levels in both transplant groups were comparable to those values found in sham-operated animals. These data indicate that fetal transplants can reverse the mnemonic deficits and restore cortical cholinergic neurochemical activity to near-normal levels in rats with nbM lesions.

Analysis of an Experimental Cortical Network: ii) Connections of Visual Areas 17 and 18 After Neonatal Injections of Ibotenic Acid

Lesions of cortical areas 17 and 18 were produced in newborn kittens by local injections of the excitotoxin ibotenic acid. In the adult this results in a microcortex which consists of superficial layers I, II and III, in the absence of granular and infragranular layers. Horseradish peroxidase, alone or wheat germ agglutinin conjugated, was injected in the microcortex or in the contralateral, intact areas 17 and 18. The microcortex maintains several connections characteristic of normal areas 17 and 18 of the cat. It receives afferents from the dLGN, and several visual areas of the ipsilateral and contralateral hemisphere. However, it has lost its projections to dLGN, superior colliculus, and, at least in part, those to contralateral visual areas. Thus some parts of the microcortex receive from, but do not project into, the corpus callosum. In addition, the microcortex maintains afferents from ipsilateral and contralateral auditory areas AI and AII which are normally eliminated in development.

Analysis of an Experimental Cortical Network: i) Architectonics of Visual Areas 17 and 18 After Neonatal Injections of Ibotenic Acid; Similarities with Human Microgyria

Lesions of cortical areas 17 and 18 have been produced in newborn kittens by local injections of the excitotoxin ibotenic acid (ibo). Twenty-four hours after an injection on postnatal days 2 or 3, the gray matter of areas 17 and 18 near the center of the injection appears completely destroyed, with the exception of a one-to-two cell-thick layer at the bottom of layer I. Intact migrating neurons and radial glia can be found light- and electron-microscopically in the region affected. During the following weeks a several hundred micron thick cortex reforms. In the adult, this cortex consists of superficial layers I, II and III as proven by cytoarchitectonics, continuity with the corresponding layers of the normal cortex and cellular composition. We believe that the recovery is due to completion of migration by neurons spared by the ibo injection. More severe destruction of cerebral cortex, i.e. complete loss of the neuronal layers or their reduction to a few cell-thick mantles can be obtained with ibo injections at the end of the second or, respectively, first postnatal week. Severity of lesion also depends on the dose of ibo injected. There are interesting similarities between the ibo-injured cortex and two human neocortical displasias: microgyria and ulegyria.

Quantitative Estimation of the Ratio of GABA-Immunoreactive Cells in Neocortical Grafts

Somatosensory anlage from 17-18 day old rat embryos were transplanted in place of the removed barrel cortex in adult rats. Six to eight months after transplantation, the grafts were either completely separated by glial scar or partly separated and partly confluent with the host neocortex. Each was studied histologically and immunostained for GABA. It was found that in partly confluent grafts the neuronal density was similar or even higher than in the host cortex, while the cell number in the separate grafts was much lower than in the nearby host cortex. The number of GABA-positive cells, however, was in all grafts significantly lower (2.9% on average) than in the normal cortex (11.8% on average).The decline in GABA-stained nerve cells was highest in separated grafts, but was somewhat less marked in transplants partly confluent with the host tissue. The possible role of partial or total deafferentation as well as the relative vulnerability of the transplanted tissue by temporary hypoxia and other metabolic disturbances are discussed as the probable factors in selective decline of GABA-ergic cells in the transplanted somatosensory cortex.

Photoreceptor Cell Rescue at Early and Late RPE-Cell Transplantation Periods During Retinal Disease in RCS Dystrophic Rats

Maximal PRC rescue was affected by RPE-cell transplantation in retinas of RCS dystrophic rats at early stages of the retinal disease, while little or no rescue was detected when transplantation was performed at late time periods.

Supranumerary Barrels Develop in the Somatosensory Cortex of Mice, After the Implantation of the Vibrissal Follicle Parts Containing Large Numbers of Receptors

In the mouse whiskerpad there is a group of vibrissal follicles arranged in five rows, which are topologically represented in the contralateral somatosensory cortex by the barrelfield.Each vibrissal follicle is a specialized sensory organ containing a large number of receptors, mostly Merkel cells.In these experiments, the parts of the vibrissal follicles containing most of the receptors were transplanted to different regions of the whiskerpad of newborn mice, to know whether “new”, supranumerary barrels could develop.The results confirm this hypothesis. However, the “new” barrels are not topologically represented in the barrelfield, as normal barrels do.

Developing Retina and PNS Segments for Transplantation Into the Adult Host Eye: Reconstruction of the Mammalian Visual System. 1. Methodology

Various techniques have been explored to determine the uses and limitations of techniques that enable the adult CNS to regenerate, but relatively little attention has been given to the consideration of a "reconstructed" visual system. Using this approach, one can design experiments to study the uses of exogenous tissues in reestablishing neuronal circuits that have been damaged. Toward this end, experiments were designed to determine whether embryonic retinal ganglion cells can project axons into a grafted PNS "bridge", and enter adult host targets that were partially deafferented. Embryonic eyes of E11, E14, E18 and E21 rats were sutured to peripheral nerve segments which served as bridges between the host eye and frontal cortex. Projections between the developing retina and the host brain could then be evaluated using HRP tracing techniques. From a methodological standpoint, the preparations are 65% effective; i.e., a viable bridge results between the embryonic eye and the host forebrain. The results presented in the accompanying paper demonstrate that the technique can yield results indicative of embryonic retinal development and axonal projection through the graft and into the host brain. This partial reconstruction of the visual system may prove a useful tool in understanding the uses and limitations of grafting in the CNS.

Fetal Medial Habenula Transplants: Innervation of the Rat Interpeduncular Nucleus

The effects of donor age and site of placement on the survival of fetal medial habenula (MH) transplants into adult rats hosts were examined. The innervation of the interpeduncular nucleus (IPN) in such cases was also examined. Explants of MH consisting of the medial-dorsal lip of the third ventricle were heldin vitrofor 1—2 days. Colloidal gold conjugated to wheat germ agglutinin was added for the last 18 hours to label the cells. Four of 16 cases with E19 derived transplants contained donor neurons. Markedly larger transplants were present in 95% of 20 cases with E16 derived transplants. Sites in the ventral midbrain were successful, while limited or no survival occurred at sites more remote from IPN. Retrograde labeling of transplant neurons was present in each case studied with HRP injection into host IPN. Colloidal gold-labeled macrophages, some oriented capillaries and GFAP-positive processes marked the donor-host interface. In EM the interface was evident only by the difference in tissue elements in the transplant versus host. Numerous synapses of Gray types I and II were present in the transplant. Excellent survival of MH neurons, donor/host interfaces, innervation of IPN by the transplant and fine structure in and around the transplants, all suggest that such preparations are suitable for further experimental analysis of the habenulo-interpeduncular system.

Intraparenchymal Striatal Transplants Required for Maintenance of Behavioral Recovery in an Animal Model of Huntington's Disease

Rats which receive injections of kainic acid (KA) into the striatum show many of the anatomical, biochemical and behavioral abnormalities seen in patients with Huntington's disease. Recently, it has been reported that fetal striatal transplants into the lesioned striatum could normalize the neurological and behavioral abnormalities produced by the KA lesion. The present study examined the issue of transplant integration in producing behavioral recovery. In one experiment, lesioned animals with transplants located within the lateral ventricle were compared against parenchymally transplanted rats. It was found that unless the ventricular transplant grew into the lesioned striatum there was no recovery. The second experiment demonstrated that electrolytic destruction of a successful fetal striatal transplant could reverse the transplant-induced behavioral recovery. These results suggest that the integrity of the transplant is important in maintaining behavioral recovery. A continuing functional interaction between the host brain and transplanted tissue may be a vital element in the success of the fetal striatal transplant.