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Biomedical subjects

D G Stein

Publications and source records attributed to D G Stein.

At least 73 records · Page 4Linked to original sources
PubMed1987

Reduction of anterograde degeneration in brain damaged rats by GM1-gangliosides.

After receiving a nigrostriatal hemitransection in the left hemisphere and an electrolytic caudate nucleus (CN) lesion in the right hemisphere, rats were given intraperitoneal injections of saline or GM1-gangliosides. Significantly smaller areas of terminal degeneration were seen in the substantia nigra pars reticulata (SNr) ipsilateral to the caudate lesion of animals treated with GM1. No statistical differences were seen in the number of degenerating terminals in the CN and SNr on the side with the hemitransection. Exogenous GM1 may thus be effective in preventing anterograde degeneration following brain injury.

Animals↗
PubMed1987

Morphologic features of embryonic neocortex grafts in adult rats following frontal cortical ablation.

Embryonic cortex from 19-day fetuses was transplanted in a medial frontal cortex wound cavity of 105-day-old male rats. Nissl-stained tissue revealed little internal laminar organization. Graft sections impregnated by the Loyez method exhibited bands of myelinated fibers surrounding implants as well as long-interconnecting and swirl-like fiber fascicles within the implant. Tissue processed histochemically for acetylcholinesterase and choline acetyltransferase revealed enzyme-positive fibers and cell bodies within the grafts. Cytochrome oxidase histochemistry revealed regional variations in the metabolic activity of the grafts. In summary, although our frontal cortex grafts exhibit many of the morphological features seen in intact frontal cortex, the organization of these components within the implant is dissimilar to normal cortical tissue.

Acetylcholinesterase↗
PubMed1987

Ganglioside-induced alterations in hippocampal cholinergic enzymes and Na,K-ATPase after fimbria-fornix transection.

Previous biochemical findings suggest that exogenous gangliosides enhance cholinergic sprouting in the hippocampus after partial lesions of the septohippocampal pathway. To assess whether GM1 ganglioside accelerates the onset of this sprouting after complete lesions, we measured cholinergic enzymes and Na,K-ATPase activity in the hippocampus of rats with unilateral fimbria-fornix transection. At 14 and 18 days postlesion, histochemical staining showed that acetylcholinesterase (AChE) was almost completely eliminated in the hippocampus ipsilateral to the transection in untreated and GM1-treated rats. Biochemical assays confirmed that GM1 treatments did not increase AChE activity in the denervated hippocampus. Rather, there were significant reductions of AChE and choline acetyltransferase activities in the ipsilateral hippocampus relative to the contralateral value (P less than .001); and the reductions were greater in GM1-treated rats than in untreated controls (P less than .001). Na,K-ATPase activity in the ipsilateral hippocampus increased by 10.1% in GM1-treated rats, whereas it decreased by 21.7% in untreated controls (P less than .05). Since Na, K-ATPase is enriched in synaptic membranes, the increased activity of this enzyme may indicate that GM1 treatments stabilize surviving synaptic membranes and/or accelerate the onset of sprouting in the denervated hippocampus. The reductions in cholinergic enzymes, however, imply that the sprouting pathway must be noncholinergic.

Acetylcholinesterase↗
PubMed1987

Gangliosides fail to enhance behavioral recovery after bilateral ablation of the visual cortex.

Postsurgical injections of GM1 gangliosides (30 mg/kg IP) reduced neither behavioral deficits in rats following bilateral ablation of the visual cortex nor the extent of retrograde degeneration of neurons in the dorsolateral geniculate nucleus that typically accompanies large lesions of the visual cortex. Our findings are in contrast to previous research, in which ganglioside treatments have been shown to enhance the rate of functional recovery after lesions in other parts of the central nervous system. The negative findings in the present experiment may be due to the disruption of normal circadian rhythms caused by occipital cortex injury.

Animals↗
PubMed1987

Effects of fimbria-fornix transection and ganglioside treatments on histochemical staining for glucose-6-phosphate dehydrogenase in the lateral septum.

The present study examined whether ganglioside treatments would affect an enzyme marker (glucose-6-phosphate dehydrogenase; G6PDH) of neural metabolism in an established model system (the hippocamposeptal projection) of deafferentation and sprouting. Rats were subjected to unilateral transections of the fimbria-fornix (FF) in order to (1) interrupt the hippocamposeptal projection, (2) deafferent the lateral septal nucleus (LSN) ipsilaterally, and (3) induce sprouting by the contralateral FF. In untreated rats which were killed at 2-4 days postlesion, histochemical staining for G6PDH was reduced by 35-40% in the deafferented LSN relative to the contralateral side. However, at 6-8 days (i.e., when sprouting begins), staining intensity returned toward contralateral values (i.e., recovered). This pattern of changes in G6PDH staining was not observed in the caudate nucleus adjacent to the LSN. In ganglioside-treated rats which were killed at 4 days, there was a significantly smaller reduction of G6PDH staining in the deafferented LSN (23%; P = .05). This effect was not observed in the LSN of treated rats killed at 2 days, nor in the caudate nucleus at either time point. The present data indicate that (1) FF transection results in a reduction and subsequent recovery of G6PDH staining in the deafferented LSN; and (2) ganglioside treatments may accelerate the onset of the recovery of G6PDH activity. We suggest that gangliosides' effect on G6PDH reflects an acute enhancement of biosynthetic events in deafferented neurons.

Afferent Pathways↗
PubMed1987

Hormonal state affects recovery from frontal cortex lesions in adult female rats.

Pseudopregnant and normal cycling female Sprague-Dawley rats were trained on a delayed-spatial alternation task. After acquisition training, the subjects received frontal cortex lesions and were subsequently tested for retention. The pseudopregnant animals with lesions were less impaired than their normal cycling counterparts. Learning and retention testing were not affected by hormonal status in the noninjured controls. Histological examination showed that the normal cycling rats with frontal cortex lesions possessed enlarged ventricles, indicating the presence of edema in this surgical group. However, brain tissue of pseudopregnant subjects given the same lesion and sham operates of both hormonal states did not display this characteristic of edema. We speculate that the behavioral and anatomical impairment observed in the normal cycling females with brain injury is due to higher levels of vasopressin, a potent vasoconstrictor synchronized with brain injury in our manipulation.

Animals↗
PubMed1985

GM1 gangliosides stimulate neuronal reorganization and reduce rotational asymmetry after hemitransections of the nigro-striatal pathway.

The effects of monosialoganglioside (GM1) injections on neuronal reorganization and behavioral recovery were studied in rats with unilateral transections of the nigro-striatal pathway. In Experiment 1, animals were treated daily with injections of saline or GM1 for not more than 14 days. At 2 days after surgery, GM1-treated animals exhibited less amphetamine-induced rotational asymmetry than did saline treated counterparts. This difference was still apparent at day 12, but vanished at postoperative day 39. Apomorphine-induced rotational asymmetry was equal in both groups at day 15, but by day 42, asymmetries increased in saline controls while remaining unchanged in GM1-treated animals. Rats were killed at either post-operative days 3, 15, or 45 after having received injections of horseradish peroxidase (HRP) into the denervated caudate nucleus. The number of neurons labelled by retrograde HRP-transport were counted in the ipsilateral substantia nigra pars compacta (iSNc), ipsilateral ventral tegmental area (iVTA), frontal cortex, and in the contralateral substantia nigra pars compacta (cSNc). Anterograde transport was also examined in the ipsilateral substantia nigra pars reticulata (iSNr). A significant loss of retrograde labelling in iSNc and iVTA was observed for both groups at post-operative day 3. At day 15, however, GM1-treated animals showed more labelling in these structures as well as in the cSNc. At 45 days after surgery comparable labelling was seen in both lesion groups. The total area of anterograde HRP-labelling in the iSNr significantly increased over time, with no differences between treatment groups. In Experiment 2, rats given the same hemitransections as in Experiment 1, were treated with daily injections of saline or GM1 for 14 days, and then received unilateral injections of 6-hydroxydopamine into the iSNc and iVTA. Nine days later, brain tissue was stained for examination of anterograde degeneration. Significantly more degenerating axons and terminals were found in the caudate nucleus of GM1-terminals were found in the caudate nucleus of GM1-treated rats than in saline-treated controls. We propose that the early reduction of behavioral deficits may be related to a ganglioside-induced reduction of secondary degeneration or edema. The effect of gangliosides on later behavioral recovery is to accelerate neuronal reorganization. This reorganization probably involves terminal proliferation of ascending, intact striatal afferents spared by the hemitransection.

Animals↗
PubMed1985

The saline effect: minimizing the severity of brain damage by reduction of secondary degeneration.

Rats with bilateral lesions in the caudate nucleus received intracerebral injections of isotonic saline directly into remaining caudate tissue. Compared with noninjected controls, saline-treated animals performed a spatial footshock task better when tested after a 9-day recovery period but not if tested shortly after surgery. Histological evaluation revealed that the saline treatment significantly reduced anterograde degeneration in substantia nigra pars reticulata. In addition, behavioral measures correlated with lesion size and degree of anterograde degeneration in saline-treated animals but not in operated controls. It seems that saline injections can prevent neuronal death in tissue surrounding the zone of trauma, possibly through an alteration of ionic properties in the extracellular space.

Animals↗
PubMed1985

Neonatal brain damage and recovery: intraventricular injection of NGF at time of injury alters performance of active avoidance.

Rats were given lesions of either the ventromedial hypothalamus (VMH) or septal nucleus at 7 days of age and then were tested repeatedly in an active avoidance task (A.A.) from 20 to 80 days. VMH rats were consistently impaired on the A.A. task beginning at 40 days of age. The animals with septal lesions performed the A.A. task consistently better than VMH or control animals throughout the entire test period, the septal syndrome becoming more pronounced as the rats reached maturity. In intact rats a single, intraventricular injection of NGF given at 7 days of age resulted in a greater reactivity, especially as the rats approached maturity. NGF, given at time of surgery, also improved performance of the A.A. task in VMH-damaged rats tested at 40-80 days. In rats given septal lesions, NGF treatment at time of injury attenuated the septal syndrome of improved A.A. performance. The data indicate that NGF treatment, given to neonatal rats, can produce long-lasting effects on CNS functions and can contribute to functional recovery from brain lesions.

Animals↗
PubMed1985

Fetal brain tissue transplants reduce visual deficits in adult rats with bilateral lesions of the occipital cortex.

Fetal brain tissue from the occipital or the frontal cortex was implanted into the damaged occipital cortex of adult rats. The animals receiving grafts of embryonic frontal cortex showed partial restoration of brightness discrimination while recipients given homologous implants of occipital cortex were as impaired as those animals with lesions alone. Neither frontal nor occipital grafts aided in the performance of a pattern discrimination problem; both groups of brain-damaged animals were unable to learn the task. Nonetheless, both groups of animals had viable and enlarged grafts with similar neuronal and glial profiles.

Animals↗
PubMed1984

Gangliosides minimize behavioral deficits and enhance structural repair after brain injury.

Injections of GM1-gangliosides (30 mg/kg, i.p.) in adult rats were shown to reduce behavioral deficits after brain lesions. This was observed (1) after bilateral electrolytic lesions of the caudate nucleus in a learning task involving negative reinforcement; (2) following aspiration lesions of the mediofrontal cortex in a learning task involving positive reinforcement; and (3) when rotational behavior was assessed after amphetamine or apomorphine injections in animals with partial hemitransections of the nigro-striato-nigral fibers. A detailed anatomical analysis of the latter study, using a retrograde tract-tracing dye wheat germ agglutinin-horseradish peroxidase (WGA-HRP), provided evidence for ganglioside-stimulated, neuronal reorganization of connections to the caudate nucleus. Our findings support the notion that gangliosides reduce behavioral deficits following brain injury by preventing secondary neuronal degeneration and/or enhancing structural reorganization of remaining afferents, rather than by influencing denervation supersensitivity.

Animals↗
PubMed1984

Sparing and recovery of spatial alternation performance after entorhinal cortex lesions in rats.

Groups of adult rats were first trained on a spatial alternation task and then subjected to unilateral entorhinal cortex lesions, unilateral entorhinal cortex lesions followed by dorsal psalterium transections, or bilateral entorhinal cortex lesions. After this surgery, the rats were then tested for retention of spatial alternation. Neither unilateral lesions alone nor unilateral lesions followed by dorsal psalterium transections resulted in long-term spatial performance deficits; however, animals with bilateral lesions exhibited severe impairments from which they eventually recovered. The results from animals with bilateral entorhinal damage indicate that extensive postoperative training may facilitate the recovery of spatial alternation performance. Histological analyses indicated that the crossed entorhinal projection proliferated in the dentate gyrus after unilateral entorhinal lesions and such anomalous growth occurred independently of any changes in alternation performance.

Animals↗
PubMed1983

Functional asymmetry of the songbird brain: effects of testosterone on song control in adult female canaries (Serinus canarius).

Previous research showed that chronic testosterone treatment of adult female canaries results in song development, demonstrating that vocal behavior is more dependent upon the presence of an appropriate hormonal stimulus than upon the genetic sex of the individual. We now report that in adult female canaries the importance of the left hemisphere for controlling testosterone induced song increases with singing experience. The occurrence of left-lateralized control of vocal behavior may prove to be a characteristic typical of animals capable of vocal learning.

Animals↗
PubMed1983

Fetal brain transplant: reduction of cognitive deficits in rats with frontal cortex lesions.

Frontal cortex and cerebellar tissue from fetal rats was implanted into the damaged frontal cortex of adults. Cognitive deficits in spatial alternation learning that follow bilateral destruction of medial frontal cortex were reduced in rats with frontal cortex implants but not in those with implants of cerebellum. Histological evaluation showed that connections were made between the frontal cortex implants and host brain tissue.

Animals↗
PubMed1983

Behavioral effects of intracerebral injections of renin and captopril in intact and brain-damaged rats.

Rats with, or without, bilateral lesions of the caudate nucleus received intracaudate injection of either renin or renin plus Captopril (SQ 14225). Following such treatment, animals were impaired on a spatial reversal task compared to controls. We concluded that the putative renin contaminant of nerve growth factor (NGF) does not contribute to behavioral recovery from brain damage observed after NGF injections in other studies. Furthermore, angiotensin II might play a possible role in mediating footshock learning and spatial reversal performance.

Animals↗