Restorative Neurology and Neuroscience - Volume 3, issue 1

Authors: Notter, Mary F.D. | Kaniuki, Marcello | Felten, Suzanne Y. | Hansen, John T. | Gash, Don M.

Article Type: Research Article

Abstract: Primate adrenal medullary cells were exposed to l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) in vitro to examine the effect of this neurotoxic agent on chromaffin cells. Chromaffin cells from monkey and humans were cultured in the presence of 100 ng/ml nerve growth factor for 1 week and then exposed to 150 μM MPTP or its active metabolite methylpyridinium ion (MPP+ ) for an additional week. Cells which had extended neurites in the presence of NGF showed no morphological effect in response to MPTP or MPP+ at the light microscopic level. However, there was a significant loss in catecholamines as seen by histofluorescence and …high performance liquid chromotography (HPLC). Electron microscopy revealed a depletion in dense-core vesicles in chromaffin cells after chronic exposure to MPTP while the mitochondria appeared similar to those observed in control cells. Replacement of MPTP medium with standard medium stimulated restoration of catecholamine histofluorescence after 7 days. An acute 15 min pretreatment of chromaffin cells with MPTP or MPP+ induced secretion of catecholamines over a 1 h pulse, with MPP+ producing the maximum and more rapid secretion as determined by HPLC. These data indicate that MPTP induces a dramatic loss in catecholamines in primate chromaffin cells in vitro after both acute and chronic exposures; however, removal of the toxic agent permits restoration of catecholamines without permanent effect on the integrity of these cells. Show more

Keywords: Cell culture, Adrenal chromaffin cell, catecholamine, MPTP, Monkey, Man

DOI: 10.3233/RNN-1991-3101

Citation: Restorative Neurology and Neuroscience, vol. 3, no. 1, pp. 1-10, 1991

Authors: Shen, Yong | Isaacson, Robert L. | Smotherman, William P.

Article Type: Research Article

Abstract: This study investigated the effects of fetal rat umbilical cord compression on anatomical, biochemical, and behavioral parameters of development. Further, the study examined the ability of the calcium channel antagonist nimodipine to afford protection from this insult. Near the day of birth (E21), the umbilical cord of individual fetuses was not clamped or clamped for 2, 6, or 12 min. Before clamping, mothers were given 70 μg/kg (i.p.) nimodipine in a polyethylene glycol (PEG) vehicle or the vehicle alone. Selected animals were sacrificed for cytochrome oxidase histochemistry. The remainder of the pups were given to foster mothers and allowed to …develop through adulthood. At the end of testing all animals were sacrificed and the brains weighed and measured. Histochemical analysis revealed that clamping resulted in a decrease in cytochrome oxidase reaction product in the hippocampus. The reduction in this marker of oxidative metabolism was not as pronounced in animals from drug-treated mothers. Alterations in behavior produced by clamping were detectable as early as the third day after birth (P3). At this age, pups subjected to cord clamping exhibited impaired righting and diminished avoidance of a ‘cliff’ on which they had been placed. On P67–P75, clamped animals exhibited hyperactivity in an open field, low rates of spontaneous alternation in a T-maze, and impaired learning and memory in a Pavlovian conditioned aversion-to-brightness test. The calcium channel blocker afforded protection from the effects of cord clamping, since the nimodipine-treated animals were less impaired in these behavioral tests. Animals that had been subjected to cord clamping showed reduced brain volumes and dimensions on P80. Nimodipine treatment normalized these parameters of brain development relative to non-clamped controls. Taken together, these results indicate that brief periods of umbilical cord occlusion near the time of birth can have both immediate and long-term effects on different parameters of development. In addition, the calcium channel blocker nimodipine affords partial protection from damage induced by compression of the fetal umbilical cord. Show more

Keywords: Prenatal brain damage, Hypoxia, Nimodipine, Anatomy, Behavioral development, Learning, Memory

DOI: 10.3233/RNN-1991-3102

Citation: Restorative Neurology and Neuroscience, vol. 3, no. 1, pp. 11-22, 1991

Authors: Sprick, U.

Article Type: Research Article

Abstract: Pyramidal neurons inside transplants of embryonic nervous tissue are capable of generating axonal extrinsic hippocampal fiber connections over considerable distances to appropriate target areas in the mature brain. The establishment of long-distance graft efferents to the lateral septum and to the entorhinal cortex was shown by retrograde transport of the tracers HRP and bisbenzimide which were injected into these areas after bilateral neurotoxic lesions of the hippocampus. Additional AChE-staining demonstrated the presence of an afferent cholinergic graft input mainly from the medial septum via the fornix. Morphological analysis of the transplants grafted as cell suspensions showed typical details of the …original hippocampus cytoarchitecture with bands of pyramidal and granule cells. Show more

Keywords: Embryonic hippocampal transplant, Entorhinal cortex, Septum, Fluorescent dye (bisbenzimide), HRP, Organotypic graft cytoarchitecture

DOI: 10.3233/RNN-1991-3103

Citation: Restorative Neurology and Neuroscience, vol. 3, no. 1, pp. 23-34, 1991

Authors: Sharkey, John | McBean, Douglas E. | Ritchie, Isobel M. | Kelly, Paul A.T.

Article Type: Research Article

Abstract: Blood–brain barrier permeability was measured using [14 C]-labelled a-aminoisobutyric acid (AIB) quantitative auto-radiography in rats which had previously received unilateral ibotenate-induced lesions of the nucleus basalis followed by intracortical implantation of foetal basal forebrain cell suspensions. The permeability characteristics of intracortical transplants were found to be dependent upon the site of implantation. Superficial transplants were invariably associated with AIB transfer constants (Ki ) 3- to 4-fold higher than those in corresponding contralateral host cortex. In transplants sited deep in host neocortex, Ki values were not significantly different from those measured in surrounding host brain tissue.

Keywords: Intracerebral transplant, Blood–brain barrier, Quantitative autoradiography, α-aminoisobutyric acid

DOI: 10.3233/RNN-1991-3104

Citation: Restorative Neurology and Neuroscience, vol. 3, no. 1, pp. 35-40, 1991

Authors: Goldstein, Larry B. | Coviello, Andrea | Miller, Gerald D. | Davis, James N.

Article Type: Short Communication

Abstract: Beam-walking in the rat provides a method for investigating the effects of drugs on motor recovery following unilateral injury to the sensorimotor cortex. In the present experiment, the impact of norepinephrine depletion on beam-walking recovery was investigated. Groups of rats were first given either the neurotoxin DSP-4 or saline. Two weeks later, the animals were trained at the beam-walking task. Rats were then subjected to either a unilateral sensorimotor cortex lesion or sham operation. Recovery of beam-walking performance was measured over the next 12 days. Pretreatment with DSP-4 significantly slowed the rate of recovery but did not significantly affect sham-operated …rats. Norepinephrine was significantly diminished in both lesioned and sham-operated rats that had been given DSP-4. These results are consistent with the hypothesis that recovery of beam-walking in the rat is mediated, at least in part, through noradrenergic neurons. Show more

Keywords: Motor recovery, DSP-4, Noradrenaline, Beam-walking, Brain injury, Stroke, Cortical lesion, Rat

DOI: 10.3233/RNN-1991-3105

Citation: Restorative Neurology and Neuroscience, vol. 3, no. 1, pp. 41-47, 1991

Article Type: Research Article

DOI: 10.3233/RNN-1991-3106

Citation: Restorative Neurology and Neuroscience, vol. 3, no. 1, pp. 49-52, 1991