Showing papers by "Santiago Ambrosio published in 1993"

Plasticity of the nigrostriatal system in MPTP-treated mice. A biochemical and morphological correlation.

Abstract: In order to compare the recovery capacity of the nigrostriatal system between adult and old mice, MPTP hydrochloride was administered to 48 BL/C57 male mice, which were sacrificed 24 h or 10 d after the second dose. The animals were divided into four groups, based on age (adult or old) and moment of sacrifice (24 h or 10 d). The detailed morphology of the neurons and the cellular processes of the substantia nigra pars compacta and the striatum were studied using the Golgi method. Immunostaining with a polyclonal glial fibrillary acidic protein antiserum using the peroxidase-antiperoxidase technique was performed to study the glial response. Striatal catecholamines were determined to correlate the biochemical data with the morphological changes. Significant neuronal changes of cellular processes were observed in substantia nigra pars compacta from all MPTP-treated mice, consisting of swelling and distortion of cellular bodies, discontinuous thickness, and nodulations of dendrites with baded aspect. Axons showing focal swelling and nodulations were also found in the neuropil of silver impregnated striata. Marked gliosis with reactive astrocytes in substantia nigra and striatum from all the old treated mice was found. Recovery was only observed in adult mice sacrificed 10 d after withdrawal. At this time, all the old MPTP-treated mice showed marked neuronal changes and a persistent marked gliosis. As expected, 24 h after the MPTP treatment, a marked depletion of dopamine and its metabolites was found in all the animals; at 10 d, the depletion was partially reversed in the adult group. These data correlate well with the observed morphological changes. Our results suggest that, in mice, deterioration of dendritic and axonal neuropil constitutes a significant causal factor of the MPTP neurotoxicity. These features are related to the age of the animals and the integrity of the plasticity phenomena, which appear to be altered in old mice.

Assessment of purine metabolism in human renal transplantation.

Abstract: Cortical levels of nucleotides and their degradation products from 42 transplanted human kidneys have been studied. Biopsies were performed during renal harvesting just before cooling, at the end of cold storage, and following reinstallment of renal blood circulation. ATP levels fell, and AMP and degradation products (inosine monophosphate [IMP], inosine, adenosine, and hypoxanthine) increased during cold storage and returned to near-normal values 30 min after recirculation. The major degradation product found was hypoxanthine, indicating very poor xanthine oxidase activity in human kidneys. The sum of adenine nucleotides (ATP+ADP+AMP) did not significantly decrease after cold storage, but adenylate energy charge (ATP+1/2ADP/ATP+ADP+AMP) was reduced to half, being recovered in implanted kidneys. The sum of adenine nucleotides was significantly reduced after implantation. The rate of acute tubular necrosis was higher in kidneys preserved for more than 30 hr. Kidneys with acute tubular necrosis had significantly lower levels of the total pool of adenine nucleotides at reperfusion, but there was no correlation between incidence of acute tubular necrosis and ATP or other metabolite levels in the kidneys before or during cold preservation. The success of human kidney transplantation does not seem to depend only on the pool of residual nucleotides at the end of cold storage but on other factors that determine the ability of the cell to recover a normal energy state after reperfusion.