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Biomedical subjects

L L Butcher

Publications and source records attributed to L L Butcher.

At least 73 records · Page 4Linked to original sources

Intracerebral 6-hydroxydopamine produces extensive damage to the blood-brain barrier in rats.

Extensive extravasation of intravenously administered horseradish peroxidase (HRP) was observed in rat brains infused intranigrally with 8 microgram/4 microliter or 4 microgram/2 microliter 6-hydroxydopamine (6-OHDA), suggesting that the cytotoxin produced widespread alterations in the integrity of the blood-brain barrier. Such damage was dose-dependent and occurred in the mesencephalon around the cannula tip, along the cannula tract, and in the cerebral cortex. The extent of HRP extravasation diminished as a function of increasing time after 6-OHDA administration. These findings indicate that alterations in blood-brain barrier permeability may contribute to the constellation of dysfunctions and possible recovery of function following intranigral infusions of the cytotoxin.

Animals↗

Cholinergic projections from the basal forebrain to frontal, parietal, temporal, occipital, and cingulate cortices: a combined fluorescent tracer and acetylcholinesterase analysis.

The morphologies, intercellular organization, and cortical projection patterns of putative cholinergic neurons in the basal forebrain of the rat were examined by use of fluorescent tracer histology in combination with the pharmacohistochemical regimen for acetylcholinesterase (AChE). Intensity staining AChE-containing cells projecting to frontal sensorimotor (Area 10), parietal (Area 2), and temporal (Area 4) cortices were found ipsilaterally in nucleus preopticus magnocellularis, in nucleus basalis, and in association with the substantia innominata, the ansa lenticularis, and the lateral hypothalamic area; an essentially rostrocaudal topography was observed for these projections. AChE-containing pathways to cingulate (Area 29) and visual (Area 17) cortices derived from ipsilateral somata associated with the vertical and horizontal limbs of the diagonal band, nucleus preopticus magnocellularis, rostral portions of nucleus basalis, and the substantia innominata. Neurons innervating Area 29 were generally located more rostrally than those giving rise to AChE afferents to Area 17. The vast majority of cells appeared to innervate relatively discrete areas of the cortex. Evidence for collateralization was found only in neurons projecting to visual and cingulate cortices, and these represented only 3.2% of the cells providing AChE afferents to Areas 17 and 29. The basal forebrain AChE projection cells were typically large (greater than 25 micron in maximum cell body extent), and their somata were predominantly oval, with lesser proportions being fusiform or triangular. Many were organized in clusters, particularly in nucleus basalis.

Acetylcholine↗

Cholinergic projections to the basolateral amygdala: a combined Evans Blue and acetylcholinesterase analysis.

The origins and acetylcholinesterase (AChE, EC 3.1.1.7) content of neurons projecting to the AChE-rich basolateral amygdala were studied by infusing Evans Blue (EB), a retrogradely transported fluorescent label, into that neural region and, following microscopic evaluation of labelled somata, staining the same tissue sections for AChE according to the pharmacohistochemical regimen. The following basal forebrain areas contained cells labelled with EB: the lateral preoptic area, ventral pallidum, nuclei of the diagonal band, medial septal nucleus, bed nucleus of the stria terminalis, and substantia innominata. The majority of the basal forebrain neurons projecting to the basolateral amygdala stained intensely for AChE, suggesting that they were cholinergic. In the brainstem, EB-labelled neurons staining intensely for AChE were found less frequently, but a few were observed in the nucleus tegmenti pendunculopontis, locus ceruleus, subcerulear region, and reticular formation. Cells accumulating EB after basolateral amygdala infusion but demonstrating no, weak, or moderate AChE activity were seen in the orbitofrontal, anterior cingulate, temporal, and insular cortices; the mediodorsal, paraventricular, and parataenial nuclei of the thalamus; the periventricular gray substance; the ventromedial mesencephalic tegmentum; the lateral and compact portions of the substantia nigra; the dorsal raphe; the dorsal tegmental nucleus; and the dorsal parabrachial nucleus. On the basis of staining intensity, intracellular organization of the AChE reaction product, and previous results in the literature, we conclude that the major cholinergic input to the basolateral amygdala derives from the basal forebrain.

Acetylcholinesterase↗

Evidence for a crossed nigrostriatal pathway in rats.

In order to characterize further the origin of striatal afferents, adult rats underwent a unilateral intrastriatal infusion of 30% Evans Blue solution (0.2 - 0.5 mul). Labeled neurons were observed in ipsilateral substantia nigra, thalamus, cortex, ventromedial mesencephalic tegmentum and dorsal raphe. Several labeled neuronal somata, albeit considerably fewer than seen ipsilaterally, were found also in the contralateral substantia nigra and ventral tegmental area, a result contrary to previously reported findings in the rat. Control injections restricted to cortex overlying striatal target site did not result in similar labeling, and corpus callosum transection prior to intrastriatal injection did not prevent labeling of contralateral substantia nigra. These findings indicate that rats, like cats, have a sparse crossed nigrostriatal pathway.

Afferent Pathways↗

Evidence for a catecholaminergic projection to area X in the zebra finch.

In the zebra finch (Poephila guttata), horseradish peroxidase injected into or near Area X of the lobus parolfactorius (LPO) is transported to cell bodies in ipsilateral hyperstriatum ventrale pars caudale (HVc), area ventralis of Tsai (AVT), and nucleus tegmenti pedunculo-pontinus, pars compacta (TPc). Area X, LPO, and paleostriatum augmentatum (PA) all contain a dense network of catacholamine-containing axons and nerve terminals, as determined in histofluorescence studies. Cell bodies in AVT and TPc contain catacholamines; lesions of TPc greatly reduce or abolish catacholamine fluorescence in PA, and a lesion of AVT eliminates histofluorescence in LPO, icluding Area X. The anatomical location and catecholaminergic projection from AVT suggest that LPO-Area X may be the avian homolog of the mammalian nucleus accumbens, olfactory tubercle, and/or rostromedial caudate.

Animals↗

Cholinergic neurons in the caudate-putamen complex proper are intrinsically organized: a combined Evans blue and acetylcholinesterase analysis.

In an attempt to determine whether or not acetylcholinesterase (AChE)-containing neurons of the caudate-putamen proper were the source of striatal efferent fibers, we infused Evans Blue, a retrogradely transported fluorescent label, into the globus pallidus, entopeduncular nucleus, substantia nigra, or retrorubral area. Following microscopic analysis of the striatum for Evans Blue-labelled somata, the same brain sections were processed for AChE according to the pharmacohistochemical regimen and, after additional microscopic evaluation, were counterstained with cresyl violet. Histology for Nissl substance revealed that the areal density of cell bodies in the caudate-putamen complex proper was about 1510 somata/mm2. Striatal neurons labelled with Evans Blue, those considered to be projection cells, were medium-sized (approximate minor and major dimensions: 11 X 14 microns), had a density of roughly 833 cells/mm2, and were predominantly oval with lesser proportions being fusiform, triangular, or round. Each of the target structures received input from approximately 55% (range = 26-78%) of the total population of striatal neurons in regions where the projection cellsions: 11 X 14 microns), had a density of roughly 833 cells/mm2, and were predominantly oval with lesser proportions being fusiform, triangular, or round. Each of the target structures received input from approximately 55% (range = 26-78%) of the total population of striatal neurons in regions where the projection cellsions: 11 X 14 microns), had a density of roughly 833 cells/mm2, and were predominantly oval with lesser proportions being fusiform, triangular, or round. Each of the target structures received input from approximately 55% (range = 26-78%) of the total population of striatal neurons in regions where the projection cells were located. The two types of AChE-containing somata in the caudate-putamen complex proper--the medium-sized, lightly staining Type A and the large, intensely staining Type B cell--had densities of 14 and 15 somata/mm2, respectively. None of the AChE neurons contained Evans Blue, indicating that they were not the source of striatal efferent fibers but rather interneurons that could be categorized best as the aspiny or sparsely spined cells described in Golgi studies.

Acetylcholinesterase↗

The actions of xylamine on central noradrenergic neurons.

The effects of xylamine (N-2-chloroethyl-N-ethyl-2-methylbenzylamine) on catecholamine content and uptake in rat brain were examined after systemic administration. Four hours after doses of 10 to 50 mg/kg i.p. of xylamine, norepinephrine uptake in synaptosomal preparations from cortex was reduced, but dopamine uptake in striatal preparations was unaffected. The levels of norepinephrine in the cortex and hypothalamus were depressed over this dose range, whereas dopamine levels in the striatum again were unaltered. The depletion of norepinephrine from the cortex and hypothalamus was also seen histologically by fluorescence histochemistry. When brain tissue was examined 10 days after a single 25 mg/kg dose, the depletion persisted in cortex and hypothalamus, and although there was a decrease in fluorescence intensity there was no clear evidence of a decreased number of catecholamine-containing processes that would have indicated neurotoxic effects. There was also no gliosis (an indicator of neuronal degeneration) in any of the brain areas or damage to the blood brain barrier. Thus, in contrast to 6-hydroxydopamine, xylamine appears to have selective action on norepinephrine systems and does not appear to be a nonselective neurotoxin.

Brain↗

Pars compacta of the substantia nigra modulates motor activity but is not involved importantly in regulating food and water intake.

Precise, bilateral radio-frequency lesions of pars compacta of the substantia nigra in rats resulted in the immediate and sustained appearance of hyperactivity, but such lesions did not produce significant alterations in food or water intake. These behavioral effects were correlated with considerable, histochemically assessed loss of dopamine terminals in the caudate-putamen complex, but dopamine innervation in nucleus accumbens and other forebrain areas was only slightly affected. The magnitude of motor activity increase was positively correlated with the degree of pars compacta involvement. Animals with lesions in the median raphe and adjacent reticular formation also displayed chronic hyperactivity. In contrast to rats receiving discrete radio-frequency lesions of pars compacta, animals with bilateral mesencephalic ablations produced by 6-hydroxydopamine (6-OHDA, 8 micrograms/4 microliters or 4 micrograms/2 microliters in combination with desipramine pretreatment) displayed poverty of movement. Furthermore, significant, dose-dependent decrements in food and water intake were seen after 6-OHDA. The nonselective component of such lesions was frequently large and irregular in shape. Occasional ablations produced by this neurotoxin, however, appeared more selective in that damage was confined primarily to pars compacta. Nonetheless, the best correlate of aphagia and adipsia associated with 6-OHDA treatment was lesion size, regardless of the extent of pars compacta or other nigral involvement. We conclude that aphagia and adipsia concomitant to 6-OHDA lesions of the substantia nigra results from the incidental destruction of extra-nigral systems. Virtually complete, but precise, lesions of pars compacta do not produce aphagia and adipsia. While our results are consistent with the notion that the substantia nigra serves an important role in the regulation of motor activity, they provide no support for the conjecture that it is importantly involved in mediating ingestive behaviors.

Animals↗

Electrophysiological and neuroanatomical studies of hepatic portal osmo- and sodium-receptive afferent projections within the brain.

Previous investigations concerning the function of hepatic sodium and osmoreceptors indicated that the activation of these chemoreceptive structures significantly affected physiological and behavioral mechanisms related to water and electrolyte homeostasis. Though anatomical studies predicted that such information should follow the previously described gustatory afferent pathy, until recently, the precise course taken by higher order hepatic afferents was unknown. The studies described herein verify anatomical predictions with regard to the central course of vagal-visceral afferents, as hepatically activated neurons were localized to two areas known to relay gustatory input. Further, horseradish peroxidase histochemical studies verified that a path between the nucleus of the solitary tract, the parabrachial nucleus and the ventrobasal complex certainly exists. In the light of recent findings regarding projections from the ventrobasal complex to the supraoptic nuclei, from the parabrachial nucleus to the supraoptic nuclei and from the nucleus of the solitary tract to the paraventricular and supraoptic nuclei it seems likely that the viscero-gustatory path which carries hepatic afferent information is the pathway responsible for the physiological and perhaps the behavioral consequences of hepatic sodium or osmotic stimulation.

Afferent Pathways↗

Locus ceruleus somata contain both acetylcholin esterase and norepinephrine: direct histochemical demonstration on the same tissue section.

In the same brain section stained first for catecholamines and then for acetylcholinesterase (EC 3.1.1.7), it was found that neuronal somata in locus ceruleus containing norepinephrine also contained the cholinergic degradative enzyme. Cell body shapes were fusiform, pyramidal, round, or oval. Maximum soma extent ranged from 10--40 micrometers, with the proportion of large diameter neurons increasing, and the smaller diameter cells decreasing, from rostral to caudal cerulear levels. Medium-sized neurons were roughly constant throughout the nucleus. Acetylcholinesterase may be associated with cerulear somata and proximal processes containing norepinephrine to inactivate a cholinergic input to that structure.

Acetylcholinesterase↗