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D M Gash

Publications and source records attributed to D M Gash.

At least 91 records · Page 5Linked to original sources
PubMed1988

Differential effects of hippocampal ablations on dispositional and representational memory in the rat.

Long-Evans rats with electrolytic hippocampal ablations exhibited chronic impairment in performance on a spatial delayed nonmatching-to-sample task in the arms of a T-maze. The same rats exhibited only mild deficits, which disappeared with practice in dispositional memory-dependent discrimination in the stem. Both types of discrimination were learned rapidly preoperatively with no marked positive or negative interaction between types of discrimination. The present results suggest that hippocampal lesions in rats have far more serious consequences on the performance of representational memory-dependent tasks than similar lesions in monkeys. In agreement with our past studies, the present experiment demonstrated that dispositional and representational memory systems in rodents have at least partially distinct anatomical substrates in brain.

Animals↗
PubMed1988

Nerve-cell grafting in Parkinson's disease.

The successful utilization of fetal nerve-cell grafts as therapeutic tools in animal models of neurodegenerative disease has prompted the first clinical attempts in parkinsonian patients in at least three countries. The extensive scientific data in rodents coupled with the first successful fetal neural grafts in monkeys with experimental parkinsonism suggest that consideration might now be given to clinical applications. Attention is also directed to the various types of donor cells that might be utilized in clinical trials for the treatment of parkinsonism, including potential benefits, risks, and limitations associated with each type of donor material. This review highlights major developments in this field as they relate to basic principles of neural grafting and discusses potential applications in humans.

Animals↗
PubMed1987

Adrenal medulla grafts enhance recovery of striatal dopaminergic fibers.

The drug, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), depletes striatal dopamine levels in primates and certain rodents, including mice, and produces parkinsonian-like symptoms in humans and nonhuman primates. To investigate the consequences of grafting adrenal medullary tissue into the brain of a rodent model of Parkinson's disease, a piece of adult mouse adrenal medulla was grafted unilaterally into mouse striatum 1 week after MPTP treatment. This MPTP treatment resulted in the virtual disappearance of tyrosine hydroxylase-immunoreactive fibers and severely depleted striatal dopamine levels. At 2, 4, and 6 weeks after grafting, dense tyrosine hydroxylase-immunoreactive fibers were observed in the grafted striatum, while only sparse fibers were seen in the contralateral striatum. In all cases, tyrosine hydroxylase-immunoreactive fibers appeared to be from the host rather than from the grafts, which survived poorly. These observations suggest that, in mice, adrenal medullary grafts exert a neurotrophic action in the host brain to enhance recovery of dopaminergic neurons. This effect may be relevant to the symptomatic recovery in Parkinson's disease patients who have received adrenal medullary grafts.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Neuroblastoma cells in neural transplants: a neuroanatomical and behavioral analysis.

The present experiments were aimed to determine the extent to which differentiated neuroblastoma cells may serve as a donor source for neural transplantation studies. Rodent-derived C1300 and human-derived LA-N-2 cells stained positively for choline acetyltransferase in vitro whether left untreated or rendered amitotic with mitomycin C/bromodeoxyuridine (Brdu) treatment. The two cell lines in both mitotic and differentiated states were subsequently transplanted into the hippocampus of rats that had previously undergone posterodorsal medial septal lesions. The undifferentiated cells continued to proliferate and formed large masses in the host brain within 7 days after implantation. When differentiated with mitomycin C/Brdu, the cells were autoradiographically visualized in large numbers 7 days following transplantation. Fewer cells were observed at the 30 and 120 test intervals. At the later time points the C1300 cells were found primarily within the host parenchyma while the LA-N-2 cells were found predominantly in the subependymal region below the hippocampus. These differentiated cells were also able to attenuate the cognitive dysfunction produced by medial septal lesions. However, an exact neurochemical mechanism cannot presently be ascribed to this effect since the cells failed to stain for choline acetyltransferase in vivo. At no time did differentiated cell grafts appear to revert to a neoplastic state nor was a significant immunological response observed. These findings, in concordance with other studies by our group, suggest that neuroblastoma cell lines may prove to be a practical source of donor tissue for neural transplants.

Animals↗
PubMed1987

Retinal transplants into the anterior chamber of the rat eye.

Developing retinas from 13-18-day fetuses and 2-day neonatal Long-Evans rats transplanted into the anterior chamber of adult eyes of the same or different strain (Lewis) survive and differentiate. Light and electron microscopic studies show that the transplants undergo histogenetic differentiation, resulting in the development of neurons and Müller glial cells and formation of nuclear and plexiform layers. Vascular connections develop between the host iris and the retinal transplant. Vessels and nerves, presumably of iridal origin, were seen on the surface of some transplants. Possible manifestations of graft rejection were monitored; signs of tissue rejection in transplants performed in the Long-Evans rats, an outbred strain, were rare and if present they were mild, at least during the survival periods of up to 91 days allowed in these experiments. Transplants into the eyes of Lewis rats were also well tolerated during the survival period. These observations indicate that retinal transplantation to the adult eye of a genetically different host can be successfully achieved and that both embryonic and perinatal retinas are suitable as donor tissue for ocular transplants. The procedure offers ample opportunities for the study of problems related to retinal plasticity.

Animals↗
PubMed1987

Selective cell death of magnocellular vasopressin neurons in neurohypophysectomized rats following chronic administration of vasopressin.

Regeneration and functional recovery of the hypothalamoneurohypophysial system (HNS) in neurohypophysectomized rats treated with either saline or vasopressin (VP) were analyzed utilizing specific immunohistochemical and physiological measures. Neural lobe ablation combined with VP administration precipitated a profound diabetes insipidus (following cessation of VP delivery) that persisted for the duration of the experiment. Diabetes insipidus was correlated with a drastic reduction in the number of VP-positive neurons in magnocellular hypothalamic nuclei. In contrast, large numbers of oxytocin (OT)-positive neurons survived neurohypophysectomy in VP-treated neurohypophysectomized rats; OT neurons accounted for the vast majority of magnocellular profiles observed in Nissl-counterstained sections. VP-immunoreactive fibers could be observed in limited quantities in the external lamina of the median eminence of VP-treated neurohypophysectomized rats, with little staining evident in the internal lamina. Saline-treated neurohypophysectomized rats exhibited the recovery of antidiuretic function characteristically seen following this lesion, with evidence of survival of considerable numbers of VP and OT neurons and median eminence hypertrophy. Both the internal and external laminae of the median eminence were densely innervated by large-caliber VP and OT fibers. Sham-operated animals receiving VP treatment did not show any long-term deficit in water metabolism, changes in the complement of VP or OT perikarya in hypothalamus, or changes in the innervation of the median eminence. Results indicate that VP treatment following neurohypophysectomy results in extensive retrograde degeneration of magnocellular VP neurons without affecting the survival of OT cells.

Animals↗
PubMed1987

Neural transplantation: potential therapy for Alzheimer's disease.

Significant progress has been made over the past decade in utilizing the techniques of neural transplantation to promote regeneration and recovery of function in the mammalian brain. The present paper reviews recent advances in our understanding of the properties and mechanisms of action of neural transplants and discusses how these advances might be applied to designing therapeutic approaches for treating Alzheimer's disease.

Alzheimer Disease↗
PubMed1986

Vasopressin administration prevents functional recovery of the vasopressinergic neurosecretory system following neurohypophysectomy.

The rodent hypothalamic neurosecretory system normally exhibits remarkable functional and structural plasticity following injury. However, the present study describes a newly observed phenomenon in which neurohypophysectomized animals receiving chronically administered exogenous vasopressin during the post-lesion period (a treatment which insures maximal renal antidiuresis over this time frame) lose all capacity for recovery of antidiuretic function. Functional deficits are accompanied by a severe reduction in the number of neurons exhibiting immunohistochemical staining for arginine vasopressin. These data indicate that the presence of neurological stimulation signaling vasopressin release may play an important role in promoting neural regeneration of the vasopressinergic component of the neurosecretory system.

Animals↗
PubMed1986

Amitotic neuroblastoma cells used for neural implants in monkeys.

The potential utility of cultured neuroblastoma cells as donor tissue for neutral implants into the mammalian brain has been examined. Cells from a human neuroblastoma cell line, IMR-32, were labeled with [3H]thymidine and chemically rendered amitotic. These differentiated IMR-32 cells were grafted into the hippocampi of five adult African Green monkeys, and graft survival was evaluated for up to 270 days after transplantation. Autoradiographically labeled grafted cells were identified in four animals. Processes from grafted cells could be followed for distances of up to 150 micrometers into the host brain. No evidence for neoplastic growth of the transplant was found. Thus, grafted neuroblastoma cells can survive for prolonged periods in the primate brain and may serve as a practical source of donor tissue for neural implants.

Animals↗
PubMed1986

Structural and functional relationships of grafted vasopressin neurons.

Fetal vasopressin neurons were grafted into adult Long-Evans rats with vasopressin deficiencies created by neural lobe ablation one week prior to implantation. Control animals and recipients with ectopic grafts still possessed significant deficits in fluid regulation 6 weeks following implantation. However, recipients with grafts fused to the host median eminence and containing magnocellular vasopressin neurons juxtaposed to the host portal vasculature showed restored peripheral vasopressin activity as measured by normal urine volumes and osmolalities. These findings suggest that structural integration of grafted neuroendocrine tissue with the appropriate target in the host brain is a necessary prerequisite for physiological activity.

Animals↗