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Biomedical subjects

G T Golden

Publications and source records attributed to G T Golden.

At least 37 records · Page 2Linked to original sources

Morphological and functional studies of rat tectal transplants.

Donor tectal tissue from fetal rats was transplanted to the tectal region of intact host newborn rats. Histological and ultrastructural characteristics of mature tectal grafts were examined with special emphasis placed on glial elements and the interface between transplant and host brain. Most transplants survived, proliferated, and differentiated to mature neurons and glial cells. Mature transplants were found to contain small and medium sized neurons which formed clusters along the transplant border. Neurites traversed the interface between transplant and host brain. There was an absence of phagocytosis, inflammatory reactions and chromatolytic neurons throughout the transplant. Classical staining techniques and GFAP immunoreactive stains revealed only mild focal astrogliosis confined mostly to the subpial and perivascular regions of the transplant-host interface. Ultrastructural examination of the transplant revealed numerous axodendritic synapses with aggregates of synaptic vesicles and well formed postsynaptic membranes. The absence of a leptomeningeal membrane at several points along the transplant-host interface may allow neurites from both sides to establish functional synaptic contacts. Single unit recording combined with anterograde WGA-HRP neuronal tract tracing was used to determine the presence and extent of host retinal innervation of tectal transplants.

Action Potentials↗

Systemic acetyl-L-carnitine elevates nigral levels of glutathione and GABA.

Amino acid and reduced glutathione (GSH) levels in substantia nigra (SN) as well as striatal monoamine levels were measured in acetyl-L-carnitine (ALCar) treated and control Swiss-Webster mice. ALCar, L carnitine, or saline were administered i.p. to mice for 5 days and mice were decapitated 24 hours following the last injection. Substantia nigra and striata were isolated within 2.5 and 3 min., respectively, and frozen immediately on dry ice. A significant dose-dependent increase of nigral GABA was observed following ALCar treatment; GABA levels were also increased by administration of carnitine. Nigral GSH levels were also increased. Striatal levels of dopamine and metabolites were not significantly affected by ALCar or carnitine. These results, suggest that ALCar may be useful in treating symptoms of neuronal dysfunction related to accumulation of metabolic waste.

Acetylcarnitine↗

MPTP and convulsive responses in rodents.

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg/kg s.c. for 5 days) to mice resulted in complete abolishment of strychnine seizure and of the tonic phase of the maximal electroshock response. Bicuculline and picrotoxin convulsions were not significantly affected by MPTP treatment. The severity of the pentylenetetrazole seizures was mildly, but significantly affected in the protective way. MPTP depleted neostriatal dopamine and its metabolites, together with hippocampal norepinephrine. No nigral neuronal loss was detected histologically. Strychnine seizures and the tonic phase of the maximal electroshock response are thought to depend mostly on hindbrain (bulbo-spinal) structures. Thus, these experiments suggest that a caudally projecting system originates from the substantia nigra, pars compacta, and/or locus coeruleus, controlling seizures that involve bulbo-spinal centers. While neostriatal dopamine depletion offers a good index of seizure resistance, its role in the protection from seizures remains to be established.

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

The prepiriform cortex in dementia of the Alzheimer type.

Histopathologic examination of the prepiriform cortex (PPC) in four documented cases of dementia of the Alzheimer type revealed increased numbers of neurofibrillary tangles and neuritic plaques. These findings indicate that some early- and late-onset cases of Alzheimer's disease may be associated with significant damage to the PPC, a relay center of the mammalian olfactory system that has extensive connections with structures concerned with cognitive and behavioral functions. Involvement of the PPC may be related to the complex neuropsychiatric manifestations observed in this disorder.

Aged↗

The epileptogenic action of 6-aminomethyl-3-methyl,1-4H-1,2,6-benzothiadiazine-1,1-diazide hydrochloride (TAG): non-specific versus specific antitaurine pathogenesis.

Cortical superfusion with 6-aminomethyl-3-methyl, 1-4H-1,2,6-benzothiadiazine-1,1-diazide hydrocholoride (TAG) at a concentration which selectively blocks taurine (Tau) action fails to modify electroencephalographic (EEG) activity, cortical neuronal firing and caudate-induced inhibition of cortical neuronal activity. Higher concentrations of TAG increase neuronal firing rate and eventually induce EEG interictal spikes that can be suppressed by topical gamma-aminobutyric acid (GABA), but not by glycine or beta-alanine. Topical Tau consistently enhances the epileptiform activity. It is concluded that specific blockade of Tau does not affect any of the physiological function under observation and that the epileptogenic effect of TAG is due to its GABA antagonistic action.

Action Potentials↗

Effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on levels of glutathione in the extrapyramidal system of the mouse.

Treatment of mice with the proximate neurotoxin MPTP depletes striatal dopamine levels. Depletion of striatal dopamine and metabolites in MPTP-treated mice is accompanied by depletion of glutathione (GSH) in the substantia nigra (SN). Striatal GSH and nigral amino acid levels were not significantly affected by MPTP. Results suggest that GSH depletion in SN may represent an index of regional vulnerability to metabolic oxidative stress and also of selective susceptibility to the toxic effects of MPTP.

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

Extent and organization of opossum prefrontal cortex defined by anterograde and retrograde transport methods.

Prefrontal cortex is commonly defined as cortex which receives afferents from the thalamic mediodorsal nucleus (MD). The extent of opossum prefrontal cortex was mapped with anterograde and retrograde axonal transport methods. The prefrontal field was found to include not only cortex on the lateral convexity of the frontal lobe as reported in earlier studies, but, in addition, cortex within the rhinal fissure and cortex on the rostral medial wall of the hemisphere. The organization of the thalamic input to the medial wall was analyzed in some detail and compared with that of the rat. The reason for this emphasis stemmed from earlier observations which suggested that a lateral, nonolfactory segment of MD, prominent in the rat and other species, may not be present in opossum MD. In the rat, the lateral segment, which constitutes approximately one-third of MD, projects to a relatively large expanse of rostral medial cortex which is also projected upon by the anteromedial nucleus. The main projection field of the lateral one-third of opossum MD is to cortex on the lateral convexity of the frontal lobe which has no input from the anteromedial nucleus and has no counterpart in the rat. Only the most lateral edge of opossum MD projects to medial cortex, to a very small field, which is also projected upon by the anteromedial nucleus. In other respects, the organization of the rostral medial cortex is similar in rat and opossum. These results suggest that, rather than being absent, an equivalent of a nonolfactory segment may be present in opossum MD but is markedly reduced in size, compared to that in rat and other species.

Animals↗

Transient seizure activity induced by acetylcarnitine.

Intracerebral injection of L-acetylcarnitine in rats induced interictal and ictal epileptic phenomena with immediate onset, lasting up to 4 h. Pretreatment with systemic atropine prevents all epileptiform phenomena. Local injection of muscimol and THIP abolish ictal events, but not single spikes. L-carnitine induced only ictal discharges with a latency of 40-90 min. Acetylcarnitine epileptogenic properties are probably related to muscarinic agonism. The transition from interictal to ictal events may involve failure of GABAergic mechanisms.

Acetylcarnitine↗

Penicillin spikes in rats. Limitations of a simple model for the study of anticonvulsants.

Direct GABA agonists that suppress spikes induced by penicillin in cats failed to do so in rats. Phenytoin and large doses of THIP increased the rate of spiking activity of the penicillin focus. Only progabide caused marked, initial, short-lasting suppression and a modest reduction of frequency of spikes for 1 hr. Homotaurine (3APS) reduced the amplitude and changed the morphology of the contralateral "mirror" spike. Antagonism of penicillin-induced spikes in rats is considered to be an unsuitable parameter for the screening of anticonvulsant agents.

Action Potentials↗

Sources of olfactory inputs to opossum mediodorsal nucleus identified by horseradish peroxidase and autoradiographic methods.

Some sources of olfactory input to the opossum mediodorsal thalamic nucleus (MD) were identified by retrograde horseradish peroxidase and anterograde autoradiographic methods. One major source originated from the olfactory tubercle and a narrow strip of piriform cortex bordering the tubercle. The tubercle-MD projection exhibited a definite spatial organization and included all except the most medial part of MD. The fact that the projection reached the most lateral and ventral extent of MD abutting the intralaminar complex suggests that the entire opossum MD may correspond to only the medial, magnocellular division in the primate and that the equivalents of both the parvocellular and paralamellar divisions may be absent.

Afferent Pathways↗

Transplantation of tectal tissue in rats. III. Functional innervation of transplants by host afferents.

Fetal tectal tissue was transplanted adjacent to the superior colliculus of neonatal rats. In mature recipient animals, ultrastructural studies provided evidence of host cortical synapses on cells within the transplants. To determine whether these synapses were functionally effective in driving transplant cells, tungsten in glass microelectrodes were used to record from single units in the transplants and the host cerebral cortex was electrically stimulated. Of the 214 tested units which were shown histologically to be within the transplants, 25 (11.7%) were orthodromically excited from host cortex at latencies of 15 ms or less (mean 7.3 ms). A further four transplant units were activated at relatively long latencies (40-300 ms). The presence of a functional host retinal input was also tested by electrically stimulating the host optic nerves. No transplant units were activated from these sites, apparently because very few electrode penetrations passed through the localized zones of optic axon distribution. The possible functional interrelationships between transplant and host are discussed.

Animals↗

Homotaurine (3 aminopropanesulfonic acid; 3APS) protects from the convulsant and cytotoxic effect of systemically administered kainic acid.

Pretreatment of rats with homotaurine (3 aminopropanesulfonic acid; 3APS), a synthetic gamma-aminobutyric acid (GABA) analog, protected from the convulsant and cytotoxic action of systemically injected kainic acid (KA). Wet dog shaking (WDS) behavior was significantly reduced. Taurine, an inhibitory non-GABA-mimetic amino acid, and muscimol (another direct GABA-agonist) reduced the number of seizures and lesions in the brain but were less effective than homotaurine. Progabide (a GABA-agonist) did not modify kainic acid effects. The neurotoxicity of kainic acid could have been due to repetitive convulsive activity. Activation of GABA-mediated inhibition is an effective, but not the determinant means of preventing KA-induced abnormalities.

Animals↗

Activating effects of homotaurine and taurine on corticoreticular epilepsy.

Homotaurine and taurine are two powerful inhibitory aminoacids with anticonvulsant properties against various experimental models of focal epilepsy. This study reports on their effects in the feline model of corticoreticular epilepsy induced by parenteral administration of large amounts of penicillin. Both aminoacids, but particularly homotaurine, remarkably potentiate epileptiform discharges in cats. Brainstem transection at the precollicular level does not modify the activation, thus ruling out the intervention of mesoromboencephalic structures in the observed effect. The opposing action of these two amino acids on focal epilepsy as compared to corticoreticular epilepsy suggests that the two types of epileptiform activity stem from very different pathophysiological mechanisms. Homotaurine is a powerful GABA agonist that exerts a central action upon parenteral administration. Other GABA analogs such as muscimol, imidazole acetic acid, and gamma-hydroxybutyrate have been reported to potentiate experimental models of spike and wave epilepsy. Thus, the activating effects of homotaurine in this epilepsy model are in keeping with the demonstrated GABAmimetic properties of the compound.

Animals↗

Ketamine activation of experimental corticoreticular epilepsy.

Generalized corticoreticular epilepsy was established in adult cats by parenteral penicillin, and electroencephalographic monitoring was carried out. Ketamine HCl was injected intravenously in doses of 2.5 to 20 mg per kilogram. If doses of penicillin were inadequate to establish typical spike-wave activity, ketamine induced the spike-wave pattern typical of much higher doses of penicillin. At doses of penicillin that established the spike-wave pattern, ketamine potentiated the spike-wave activity and sometimes induced spike-and-wave status. These findings suggest caution in the clinical use of ketamine in patients with corticoreticular epilepsy. Because analogous effects have been observed upon administration of GABA-mimetic agents, GABA systems may play a role in ketamine anesthesia and corticoreticular epilepsy. Precollicular brain transections failed to modify ketamine effects, excluding a possible influence of mesencephalic centers on the observed potentiation.

Animals↗

Cortical projections of the thalamic mediodorsal nucleus in the rabbit.

The cortical projection of the thalamic mediodorsal nuclear complex (MD) in the rabbit was mapped retrograde horseradish peroxidase and anterograde tritiated proline techniques. The projection field occupied the entire medial wall rostral to a mid corpus callosal level, wrapped around the frontal pole onto the lateral convexity and tailed off caudally on the dorsal bank of the rhinal sulcus. The projection of the lateral approximately one-half of MD, the half which does not receive olfactory input, was confined to medial cortex supply all but the most rostral region. This projection field of lateral MD was precisely organized in two dimensions with the most lateral part projecting most caudally and the most dorsal part projecting most ventrally. A representation for the third, anterior-posterior (A-P), dimension was not evident since any cortical point within the field was supplied by a cylinder of cells extending the entire A-P extent of lateral MD. The medial half of MD, which does receive olfactory input, projected to the remaining rostral medical cortex, the lateral convexity and rhinal sulcal region. The inverse dorsoventral relationship was partially preserved and on overlapping A-P gradient was present with sulcal projections originating more caudally in medial MD and the rostral medial projection originating more rostrally.

Animals↗

The distribution of olfactory input in the opossum mediodorsal nucleus.

Discharges of single cells in the thalamic mediodorsal nucleus (MD) of the opossum were recorded during electrical stimulation of the lateral olfactory tract. Responsive sites were histologically localized throughout the entire mediolateral extent of MD. In both rabbit and squirrel monkey responses are confined to the medial half of MD. Thus the lateral non-olfactory nuclear subdivision, common to both rabbit and squirrel monkey, was not found in the opossum. Firing patterns of cells were similar to those observed in rabbit and squirrel monkey. They commonly consisted of an early spike or burst of spikes, followed by a period of inactivity and then, in many cells, by a later period of response or of resumed spontaneous activity. The results indicate that olfactory input is characteristic of MD in a diverse sample of mammals but that topographic organization of the input is distinctly different in the opossum.

Animals↗