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On the origin of dynorphin A and alpha-neo-endorphin in the substantia nigra.

The substantia nigra contains among the highest dynorphin A (Dyn A) and alpha-neo-endorphin (alpha-Neo) concentrations in the central nervous system. No dynorphin positive cell bodies are found there, only a dense network of nerve fibers and terminals. The present study provides evidence that the Dyn A and alpha-Neo in the substantia nigra are in neural processes arising from cells located in the head of the caudate nucleus. This neuronal system has been characterized by assaying Dyn A and alpha-Neo in the substantia nigra after a number of surgical transections of neuronal pathways in the rat forebrain and midbrain. Fibers containing dynorphins and neo-endorphins seem to pass through the internal capsule, ansa lenticularis, and medial forebrain bundle on their way from the striatum to the substantia nigra.

Animals↗

Treatment of stroke with opiate antagonists--effects of exogenous antagonists and dynorphin 1-13.

We studied the effects of acute and long-term, continuous administration of six opioid compounds--naloxone, naltrexone, diprenorphine, leucine enkephalin, dynorphin 1-13, and dynorphin 3-13--on neurologic function, survival, and infarct size in a feline model of acute focal cerebral ischemia. Acutely, naloxone, naltrexone, and diprenorphine significantly improved motor function over baseline scores; the other drugs and saline (control) had no effect. In the long-term condition, no substance administered significantly affected level of consciousness, sensory function, or pupillary reactions. Naloxone, naltrexone, and dynorphin 1-13 significantly prolonged survival (p less than 0.1); the other substances had no effect. Evaluations of cat brains postmortem showed that the infarcts involved the sensory and motor cortex, internal capsule, and caudate nucleus. Infarct size was unaltered by any treatment administered; results among groups were remarkably similar. In evaluations of opiate receptor binding characteristics, high-affinity binding of ekylketocyclozocine was significantly reduced in the right (occluded) side of the cortex. Dynorphin 1-13 given 8 h postocclusion but before sacrifice increased this binding affinity to the previous level in non-occluded cortex. The observed protective effect of dynorphin 1-13 warrants further investigation. Our results support the involvement of endogenous opioid peptides in the pathophysiology of cerebral ischemia and suggest that, administered appropriately, opiate antagonists may be useful in the treatment of focal ischemic neurologic deficits.

Acute Disease↗

Computed tomography in experimental allergic encephalomyelitis--preliminary results.

Four dogs were immunized with a mixture of spinal cord homogenate and complete Freund's adjuvant. One of these dogs developed hyperacute allergic encephalomyelitis. Cranial computed tomography in this animal demonstrated a low absorption area in the internal capsule that corresponded to the pathologic lesion. Computed tomography scanning may be a useful tool in monitoring experimental allergic encephalomyelitis.

Animals↗

In vitro labeling of axonal projections in the mammalian central nervous system.

Horseradish peroxidase crystals or HRP-NP40 detergent chips were directly applied to brain slices from mice to label primary afferent fibers and their terminal arbors in the brainstem trigeminal complex, and neurons of the ventrobasal complex of the thalamus, their axons in the internal capsule, and their terminals in the primary somatosensory cortex. Anterograde and retrograde labeling of fibers, as well as retrograde labeling of somata, were observed. In vitro labeling of selected non-trigeminal structures and fiber pathways was also demonstrated. Experimental variables have been dealt with in some detail, as have specific advantages and disadvantages of the technique. This in vitro HRP labeling method for neuronal fiber systems is a useful adjunct to currently employed in vivo labeling techniques in the mammalian central nervous system.

Animals↗

Somatotopic analysis of fibre and terminal distribution in the primate corticospinal pathway.

This is an anatomical study of the precision of fibre and terminal orderliness in the direct corticospinal projection. It was conducted to assess the degree of somatotopy in this projection in primates and to deduce the mechanism(s) possibly responsible for guiding fibres to their segmental destinations in development. As fibres leave the cortex they are grouped in an orderly way so as to be placed (within the pathway cross-section) according to their points of origin. Systematic neighbourhood relations are rather abruptly broken down as the descending pathway traverses the pons. Fibres are randomly distributed within each medullary pyramid and this disorderliness is maintained throughout the spinal pathway in the dorsolateral columns. Nonetheless, fibres exciting thumb movements end selectively at cervical levels. Fibres exciting foot movements end preferentially at lumbar levels but also show a secondary maximum of terminations in cervical segments, with relatively few terminations at intervening thoracic levels. These two sets of fibres ('thumb', 'foot') are derived from distinct, separate subareas of motor cortex and pass through exclusive, separate zones of the internal capsule. Thus, developmental contact guidance between somatotopically originating neighbours is inadequate to account for the observed specificity of corticospinal fibre destinations. Fibres must be observing distinctive local segmental cues (perhaps of cytochemical nature) and/or utilising somatotopically distinctive arrival sequencing (i.e. securing specific destinations without neuronal recognition).

Animals↗

Observations on the development of certain ascending inputs to the thalamus in rats. I. Postnatal development.

We have studied the postnatal development of the major ascending afferents to the thalamus in postnatal rats using tetramethylbenzidine histochemistry following wheat germ agglutinin-conjugated horseradish peroxidase injections into either the dorsal column nuclei, the deep cerebellar nuclei, or the inferior colliculus. By the day of birth, the efferents from each of these regions have already entered, and arborized extensively within, their appropriate thalamic relay nuclei. However, the overall distribution of each of these ascending afferent systems differs dramatically from that seen in mature rats. In neonatal rats, a substantial proportion of the ascending axons extend beyond the thalamus and often enter the internal capsule, some bypassing the thalamus altogether. In addition, some of the axons which enter and arborize within the thalamus extend beyond their appropriate terminal field into adjoining thalamic nuclei. Retrograde tracing experiments utilizing Fast blue indicate that the cells of origin of these overshooting axons are distributed similarly to the cells of origin of the definitive thalamic afferents. These early erroneous projections are all subsequently eliminated and the characteristically restricted adult distribution of each afferent system is evident by P30. These results indicate that developmental overgrowths and targeting errors of thalamic afferent fibers are not unique to the visual system (where they have been documented previously), but may be a general feature in the development of these pathways.

Afferent Pathways↗

Developmental profile of non-heme iron distribution in the rat brain during ontogenesis.

The entry of iron from blood into the developing rat brain was studied by means of non-heme iron-histochemistry. The content of non-heme iron in the endothelial cells was manifest already from E14, declined from P3 to P5, and was almost absent on P10-P15. The choroid plexus epithelial cells of either ventricle was non-heme iron-containing from E14. Non-heme iron-containing macrophages situated in the stroma of the choroid plexus were also observed from E14. From E19, the macrophage-like cells tended to invade into (a) regions with transitory structures like the intermediate zone of the cerebral hemisphere, (b) developing axonal tracts like corpus callosum and internal capsule, and (c) deep layers of the tectum, a region with an extensive degree of naturally occurring cell death. The amoeboid macrophage-like cells observed in the brain parenchyma gradually acquired prolonged extensions and apparently differentiated into ramified microglia-like cells, which later lost their non-heme iron-content. Thus, at P70, non-heme iron-positive microglia-like cells were hardly seen reflecting the transitory event of non-heme iron in microglia-like cells. At P200, non-heme iron-containing microglia cells and oligodendrocytes appeared in manifestly higher number than at P70, a phenomenon probably related to aging. These results delineate for the first time the appearance of iron in the developing brain. The results are of relevance for understanding the potential of iron-deficiency for harming the developing central nervous system, generally by decreased transport of iron through brain capillaries and choroid plexus, and specifically by an impaired modulation of the developing brain parenchyma by iron-containing macrophages.

Aging↗

Long duration Jakob-Creutzfeldt disease.

The first patient was a woman hospitalized at the age of 43 years; she received the diagnosis of presenile dementia because of a progressive deterioration of her intellectual functions over an interval of 3 years. On admission there were no localizing neurological findings. During the ensuing years she became unable to speak and was no longer able to respond to commands. Death occurred at the age of 46 years from bronchopneumonia. The brain showed marked atrophy of the frontal lobes, moderate in the temporal lobes. The anterior horns of the lateral ventricles were greatly dilated. Microscopically cortical atrophy was severe, with marked depletion of neurons in involved regions. Lamination and polarity were not preserved. There was considerable increase of astrocytes and microglia, and focal sponginess was prominent. The hippocampus showed atrophy of Sommer's sector and subiculum. There were no neurofibrillary tangles and no argyrophilic plaques. The occipital sections showed little neuronal loss and no increased astrocytes or sponginess. The insulae showed neuronal loss and gliosis. There was bilateral atrophy of the caudate nuclei and globus pallidus adjacent to the dystrophic anterior limbs of the internal capsule. In the brain stem the frontopontine tracts were partially demyelinated and showed reactive gliosis. Ventral horns were atrophic with moderate glial reaction. In the second patient the microscopic changes were quite similar to those in Case 1, but there was more severe degeneration of the corticospinal tracts and the ventral horns of the spinal cord which showed considerable loss of neurons and degenerative changes in the remaining nerve cells and nerve fibers. There were many instances of axonal degeneration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Regional differences in the cat caudate nucleus as to the effectiveness in inducing contraversive head-turning by electrical stimulation.

An attempt was made to re-examine regional differences in the cat caudate nucleus as to the effectiveness in inducing contraversive head-turning by electrical stimulation and to analyze the time course of head-turning quantitatively. In 5 of the total 9 cats, the right sensorimotor cortex and its surrounding areas had been ablated chronically. While the awake, unrestrained cat maintained a stable standing posture facing forward, stimulation was applied systematically to various points in and around the caudate nucleus with a movable stimulating electrode. Trains of stimulating current pulses of less than 300 microA were given, mostly at a rate of 100 Hz for 5 s. In most experiments in which stimulation was given to the side of the intact cerebral cortex, stimulation of caudal portions of the head of the caudate nucleus was effective in inducing contraversive head-turning, but that of its rostral portions was ineffective. In experiments on the side of chronic cortical ablation, similar results were obtained. These results suggested that head-turning induced by stimulation of the caudate nucleus was brought about not by the activation of the corticofugal fibers from these cortical areas by a current spreading to the internal capsule, but by the activation of caudate neurons. Hence, it was demonstrated that there were regional differences in the cat caudate nucleus as to the effectiveness in inducing head-turning. The mean of the shortest latencies of the onset of head-turning for individual stimulation points was 396 ms (S.D., 210 ms) for the side of the intact cerebral cortex, and 454 ms (S.D., 289 ms) for the side of the cortical ablation. Statistically, there was no significant difference between them. Therefore, it was further revealed that the elimination of the sensorimotor cortex did not affect the caudate-induced head-turning in terms of the latency of its onset.

Animals↗

Organization of central cholinergic neurons revealed by combined in situ hybridization histochemistry and choline-O-acetyltransferase immunocytochemistry.

Digoxigenin-labeled riboprobes and in situ hybridization of choline-O-acetyltransferase mRNA, both alone and in combination with immunohistochemical procedures for the synthetic enzyme of acetylcholine, were used to map the topography of putative cholinergic neurons in the rat central nervous system. Only the anti-sense riboprobe yielded specific labeling, which was absent in brain sections processed with sense riboprobe. Telencephalic neurons demonstrating the mRNA for choline-O-acetyltransferase and choline-O-acetyltransferase-like immunoreactivity were found in the caudate-putamen nucleus, nucleus accumbens, olfactory tubercule, Islands of Calleja complex, medial septal nucleus, vertical and horizontal limbs of the diagonal band, substantia innominata, nucleus basalis, and nucleus of the ansa lenticularis, as well as occasionally in the amygdala. Neurons in the cerebral cortex, hippocampus, and primary olfactory structures did not demonstrate hybridization signal, even though some cells in those areas were observed to exhibit choline-O-acetyltransferase-like immunopositivity. Thalamic cells were devoid of hybrido- and immunoreactivity, with the exception of several neurons located primarily in the ventral two-thirds of the medial habenula. A few cell bodies labeled with riboprobe and co-localizing choline-O-acetyltransferase-like immunopositivity were found in the lateral hypothalamus, caudal extension of the internal capsule, and zona incerta. Neurons in the pedunculopontine and laterodorsal tegmental nuclei evinced moderate hybridization signal, whereas cells of the parabigeminal nucleus were very weakly reactive. In contrast, motor neurons of the cranial nerve nuclei demonstrated high levels of choline-O-acetyltransferase mRNA and choline-O-acetyltransferase-like immunoreactivity. Putative cholinergic somata in the ventral horns and intermediolateral cell columns of the spinal cord and around the central canal were also labeled with riboprobe. It is concluded that hybridocytochemistry with digoxigenin-labeled riboprobes confirms the existence of cholinergic neurons in most of the neural regions believed to contain them on the basis of acetylcholinesterase pharmacohistochemistry and choline-O-acetyltransferase immunocytochemistry, with the prominent exceptions of the cerebral cortex, hippocampus, olfactory bulb, anterior olfactory nucleus, and caudal raphe nuclei, which apparently do not possess neurons expressing detectable levels of the mRNA for the synthetic enzyme of acetylcholine.

Animals↗

Degeneration of hippocampal fibers and spatial memory deficit in the aged rat.

Old and young Fisher 344 rats were compared for their ability to learn a delayed alternation task. The old animals displayed significant impairment of alternation learning, and were slower than the young animals. The brains of these animals were examined using a silver degeneration stain, and among old rats there was conspicuous degeneration. The greatest density of degenerating fibers was seen in the hippocampus and in anatomically related tracts, but there was substantial fiber staining in the corpus callosum, anterior commissure, and internal capsule. Examination of the young brains revealed only an occasional fiber. There were no signs of cortical atrophy in the old animals. The histopathology of the aged animals' hippocampus and fiber tracts supports the possibility that the delayed alternation impairment shown by these animals was a result of age related degenerative changes.

Aging↗

Emotional responses to subcortical electrical stimulation in psychiatric patients.

Subcortical electrical stimulation was applied to the prospective surgical target area during 158 stereotactic operations in 135 psychiatric patients. The following target areas were studied: rostral cingulum below and in front of the genu of the corpus callosum (52 cases) genu (46) cingululum just above the genu (11) middle cingulum (6) anterior internal capsule (33) subcaudate region, 'substantia innominata' (10 cases). Forty-seven per cent of the cases reacted to stimulation with subjective emotional sensory responses. Stimulation of differ targets had significantly different results. Responses were obtained most frequently from the cingulum and genu, and least frequently from the anterior capsule and subcaudate regions. Stimulation of the rostral cingulum often caused 'negative' responses, i.e. an increase in or the appearance of anxiety and tension (11/15 cases). The opposite was true of the adjacent genu of the corpus callosum; on stimulation of this structure anxiety and tension disappeared or diminished (18/19 cases). Schizophrenic patients experienced such 'positive' responses significantly more often than non-schizophrenics. In non-anesthetized patients autonomic reactions were very rare.

Adolescent↗

Capsular ataxic tetraparesis.

A 42-year-old man with ataxic tetraparesis is reported. Computerized tomography showed bilateral and symmetrical lacunar infarcts at the junctions of the posterior limb of the internal capsule and the corona radiata. Previously this clinical syndrome had been reported only with a lesion in the pons.

Adult↗

Fabry's disease presenting with stroke.

An atypical patient with Fabry's disease is presented. This patient developed a left internal capsule lacunar stroke at the age of 25. The etiology of the stroke was unclear. At the age of 29 he was discovered to have corneal lesions suggestive of Fabry's disease but had no other clinical features typical of Fabry's disease. The diagnosis of Fabry's disease was confirmed biochemically. Fabry's disease should be included in the differential diagnosis of stroke of unclear etiology in young male patients.

Adult↗

Central nervous system lymphoma presenting with ataxic hemiparesis: a case report.

An 81-year-old man with central nervous system (CNS) lymphoma presenting with acute, progressive ataxic hemiparesis. Computed tomography and magnetic resonance imaging localized the lesion extending from the right internal capsule to the ventrolateral aspect of rostral midbrain tegmentum. A stereotactical biopsy yielded a microscopic diagnosis of medium-sized diffuse B-cell lymphoma. Although the most frequent cause of the syndrome of ataxic hemiparesis is a lacunar type of cerebral infarction, this article emphasizes that CNS lymphoma can produce the syndrome.

Aged↗

Disappearance of essential tremor after small thalamic hemorrhage.

Stereotactic thalamotomy has been reported to be effective in the control of various tremors, including essential tremor. We report a 69-year-old female who experienced spontaneous thalamotomy with a small thalamic hemorrhage, resulting in disappearance of essential tremor on the contralateral side to the hematoma, which involved the nucleus ventralis intermedius (Vim) of the thalamus and a portion of the posterior limb of the internal capsule.

Aged↗

Basal ganglionic angioleiomyoma.

A rare case of basal ganglionic angioleiomyoma in a 12-year-old girl is reported. She presented with features of raised intracranial tension, multifocal seizures, left hemidystonia and apraxia of eyelid closure. Cranial CT scan showed a large hypodense lesion with an enhancing mural nodule in the region of head of the caudate nucleus on the right side. The lesion was extending to the posterior limb of internal capsule postero-medially and to globus pallidus laterally. Another small, hyperdense, enhancing lesion was seen in the region of globus pallidus on the left side. The right basal ganglionic mass was excised through frontal craniotomy. Histopathological, Immunocytochemical and Ultrastructural examination of the right basal ganglionic mass showed features characteristic of angioleiomyoma. Following surgery the patient improved initially with respect to dystonia but worsened later on. Repeat cranial CT, 20 months after surgery, showed bilateral frontotemporal atrophy without any tumor recurrence while the lesion on the left side remained quiescent.

Angiomyoma↗

Loss of striatal neurons after local microinjection of colchicine.

Intrastriatal injections of colchicine (4 micrograms) produced irreversible striatal damage characterized 30 days later by loss of intrinsic striatal neurons, gliosis and shrinkage but no apparent damage to myelinated bundles of the internal capsule. This neuronal loss was associated with a dramatic reduction of striatal and nigral glutamate-decarboxylase (GAD), the marker of GABA-ergic synapses and of striatal choline-acetyltransferase (CAT), the marker of cholinergic synapses. The levels of dopamine (DA) and serotonin (5HT) in the striatum as well as those of their metabolites were also reduced, indicating that colchicine exerts toxic effects also on terminals of striatal afferent neurons.

Animals↗