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PubMed1990

Ultrasound and the blood-brain barrier.

High intensity focused ultrasound was employed to modify the permeability of the normal feline and canine blood-brain barrier (BBB) to a circulating vital dye--Evans blue (EB). The threshold doses (W sec/cm2) for focally increasing the permeability of the BBB in white matter (WM) and gray matter (GM) were as follows: internal capsule (WM)--340 to 680; thalamus (GM)--approximately 1326; and caudate nucleus (GM)--2284 to 2952. In the presence of supralesioning doses of ultrasound, the cross sectional area occupied by the EB was consistently greater than that of the attendant nonhemorrhagic lesion--thus suggesting that BBB changes may be inducible at sublesioning doses. These findings, in conjunction with those of others, suggest that high intensity focused ultrasound may have a role in the treatment of brain tumors based on cell destruction by two mechanisms: (a) direct, by the ultrasound and (b) indirect, by an antineoplastic agent which is delivered via an ultrasonically modified BBB.

Animals↗

PubMed2003

Deep brain and motor cortex stimulation for post-stroke movement disorders and post-stroke pain.

Our experience of deep brain stimulation (DBS) and motor cortex stimulation (MCS) in patients with post-stroke movement disorders and post-stroke pain is reviewed. DBS of the thalamic nuclei ventralis oralis posterior et intermedius proved to be useful in more than 70% of patients with post-stroke involuntary movements (hemiballismus, hemichoreo-athetosis, distal resting and/or action tremor, and proximal postural tremor). The effect of DBS of the thalamic nucleus ventralis caudalis or internal capsule on post-stroke pain was usually disappointing. Excellent pain control can be achieved by MCS in approximately 50% of patients with post-stroke pain. In the course of clinical trials on MCS for the control of post-stroke pain, it was found that co-existent post-stroke involuntary movements (hemichoreo-athetosis and resting tremor) could also be controlled by MCS. Post-stroke involuntary movements, especially those in thalamic syndrome, are sometimes associated with post-stroke pain. In such disorders, involuntary movements are attenuated, but the pain in the same patients is often exacerbated by DBS of the thalamic nuclei ventralis oralis posterior et intermedius. MCS could be the therapy of choice under such circumstances. Subjective improvement of voluntary motor performance, which had been impaired in association with mild or moderate hemiparesis, was reported during MCS by approximately 20% of patients with post-stroke pain. Such an effect on voluntary motor performance appears to be caused by an inhibition of their rigidity. The reversibility of DBS and MCS makes them an important option for the control of post-stroke movement disorders and post-stroke pain.

Electrodes, Implanted↗

PubMed1980

An autoradiographic study of the striatofugal fibers in the monkey.

Anterograde labelling with 3H-leucine was used to study the course and termination of striatofugal fibers in the monkey. Following injection of the isotope in the most medial part of the head and the body of the caudate nucleus fibers were traced along the ventrolateral part of the internal capsule and within the medial part of the comb bundle before penetrating the rostromedial pole of the substantia nigra (SN). Fiber endings were found along the dorsomedial edge of both divisions of the pallidum and in approximately the medial third of the SN over the whole length of this structure. Injection in the rostromedial part of the putamen resulted in silver grain concentrations representing labelled terminals in the central part of both divisions of the pallidum and in the ventrolateral and central part of the SN. Isotope concentration was equally important in both parts, reticulata and compacta, of the SN. These results favour the existence of rostrocaudal and mediolateral topographical relationships between, on the one end, the neostriatum and, on the other end, the pallidum and the SN.

Animals↗

PubMed1988

Regarding the experimental neurophysiological basis of psychosurgery.

A survey is given, on reports in the literature and personal experiences, on the neurophysiological basis of psychosurgery. Animal experiments as well as clinical-experimental observations in human beings are reviewed, following the usual present day targets: frontal lobe, cingulum, amygdala, thalamic and hypothalamic areas and anterior internal capsule. As a result, it has to be stated that there are no definite data resulting from animal experiments which could sustain the neurophysiological basis of psychosurgery. For psychiatric diseases animals are definitely not an adequate model. Therefore it is considered to be our neurosurgical duty to collect experimental data in human beings in a methodically proper manner and with respect to our ethical precepts.

Amygdala↗

PubMed1990

MR evaluation of calcium entry blockers with putative cerebroprotective effects in acute cerebral ischaemia.

MR imaging and spectroscopy were used to investigate whether two calcium channel entry-blockers, nicardipine and RS-87476 (Syntex), would reduce ischaemic brain damage in barbiturate-anaesthetized cats subjected to permanent unilateral occlusion of the middle cerebral artery (MCA). The evolution of cerebral injury was assessed in vivo in a total of 38 cats using a combination of diffusion-weighted and T2-weighted spin-echo proton MR imaging and phosphorus 31 (P-31) and proton (H-1) MR spectroscopy for up to 12 h following arterial occlusion. Immediately thereafter, the volume of histochemically ischaemic brain tissue was determined planimetrically. In untreated control animals, diffusion-weighted MR images obtained with strong gradient strengths (5.5 gauss/cm) displayed increased signal intensity (oedema) in the ischaemic MCA territory less than 45 min after stroke. These changes were closely correlated with the appearance of abnormal P-31 and H-1 metabolite levels evaluated with surface coil MR spectroscopy. Cats injected with i.v. nicardipine (10 micrograms/kg bolus, 8 micrograms/kg/h maintenance) or RS-87476 (2-50 micrograms/kg bolus, 0.7-17.5 micrograms/kg/h maintenance) showed a significant reduction in ischaemic injury in the ipsilateral cerebral cortex, internal capsule and basal ganglia. The results of this study suggest that these calcium entry blockers protect against brain damage induced by acute stroke by stabilizing cellular metabolic processes, reducing lactate formation in ischaemic tissues, and attenuating cytotoxic and vasogenic oedema.

Acute Disease↗

PubMed1994

Blood-borne macromolecule induces FGF receptor gene expression after focal ischemia.

We have detected fibroblast growth factor receptor (FGFR) gene expression in the focal ischemia model. The FGFR gene expression in neurons can be explained by neuronal network disturbances, but the mechanism of astroglial gene expression remains uncertain. We speculated that blood-borne edema fluid may activate gene expression of astroglias. To prove this hypothesis, we compared the pattern's of gene expression of FGFR and distribution of edema fluid by using serial tissue sections of the middle cerebral artery (MCA) ischemia. The left MCA of twenty-four male Wistar rats were occluded, and sacrificed 1, 3, 4, 7 and 14 days later by transcardiac perfusion and fixation. The tissues were sliced thinly to 14 microns sections. Part of the tissue sections was used for in situ hybridization for rat FGFR with [35S]labeled RNA probes. The other part of the sections was used for immunostaining for albumin, immunoglobulin G (IgG) and IgM. The FGFR mRNA expression was evident in the lesion-side hemisphere. In the cortex, neurons mainly expressed FGFR gene in the cortex, whereas astroglias and capillary endothelium expressed FGFR in the corpus callosum and internal capsule. The albumin distributed cortex and white matter of the lesion-side and it extended to the contralateral side. The IgG distributed mainly in the lesion-side white matter, and in part extended to the contralateral side. The IgM only distribute to the infarcted area. When we compared topographical distribution of FGFR in the white matter and pattern of albumin, IgG and IgM distribution, pattern of IgG distribution correlated well to the area of FGFR expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Identification of intracranial liqor metastases of experimental stereotactically implanted brain tumors by the tumor-selective MRI contrast agent MnTPPS.

Two cases of stereotactically induced and spontaneously metastasizing neoplasms in the rat and the cat brain are reported. In the rat, a malignant Schwannoma derived from initially supratentorially implanted RN6 cells developed a second tumor in the posterior cranial fossa. In the cat, a highly malignant polymorphous anaplastic glioma induced by implantation of cloned rat glioma cells (F98) into the left internal capsule developed small tumor cell nests along the ependyma of the ipsilateral ventricle. In precontrast magnetic resonance imaging (MRI) of both cases, the primary tumor was detectable only by a very weak hypointensity and through a shift of the midline. No metastases were apparent. Application of the metallated paramagnetic porphyrin derivative manganese(III) tetraphenylporphine sulfonate (MnTPPS) resulted in a remarkable contrast enhancement between tumoral and normal tissue, which was evident not only in the primary tumor but also in the small metastases. These observations demonstrate for the first time that MnTPPS is an efficient MRI contrast agent for the detection of metastases from primary brain neoplasms and, in consequence, support the hypothesis of its selective binding to tumor cells.

Animals↗

PubMed1995

Alpha calcium/calmodulin-dependent protein kinase II immunoreactivity in corticospinal neurons: combination of axonal transport method and immunofluorescence.

A combination of either retrograde or anterograde fluorescent tracer and immunofluorescence histochemistry using the monoclonal antibody specific for the alpha isoform of calcium/calmodulin-dependent protein kinase II (CaM kinase II alpha) was employed to test whether CaM kinase II alpha is expressed in somata of corticospinal neurons and their axons over their whole course. After the injection of carbocyanine dye DiI into the hindlimb area of the primary motor cortex of the rat, corticospinal axons and their terminal arbors were anterogradely labeled: DiI-labeled corticospinal fibers proceeded caudally in the ipsilateral internal capsule, cerebral peduncle and medullary pyramid, crossed at the pyramidal decussation and descended in the ventralmost area of the contralateral dorsal funiculus of the spinal cord. These DiI-labeled corticospinal axons expressed strong CaM kinase II alpha immunoreactivity along their course. However, their terminal arbors within the gray matter of the lumbar cord were very weakly immunostained. With the injection of Fast Blue into the lumbar enlargement of the rat, somata of corticospinal neurons in layer V of the motor cortex were retrogradely labeled. The subsequent immunofluorescent histochemistry revealed that more than 80% of Fast Blue-labeled corticospinal neurons were immunostained with CaM kinase II alpha antibody. The present immunohistochemical study demonstrated that CaM kinase II alpha is strongly expressed in both somata and axons of a majority of corticospinal neurons, although we could not detect this enzyme in the corticospinal terminals in the spinal target areas.

Amidines↗

PubMed1983

Morphological studies on neuroglia. VII. Distribution of "brain macrophages" in brains of neonatal and adult rats, as determined by means of immunohistochemistry.

Immunohistochemical studies with the use of the peroxidase-antiperoxidase (PAP) method revealed that "amoeboid microglial cells", in the brains of neonatal rats and "brain macrophages" in lesioned brains of adult rats react positively to an antiserum raised against macrophages. In brains of neonatal rats, "amoeboid microglial cells" stained by means of the PAP-method were observed in the corpus callosum, internal capsule, dorso-lateral region of the thalamus, subventricular zone of the lateral ventricle, and the subependymal layer of the ventricular system. These cellular elements were not detected in brains of rats aged 21 days or older. Resting microglial cells displaying a typical ramified structure were not specifically stained. Cells reacting positively to the macrophage antiserum appeared (i) in the cerebral cortex of adult rats following placement of a stab wound, or (ii) in the hippocampal formation after kainic acid-induced lesions; in the damaged areas immunoreactive cells exhibited the typical features of "brain macrophages". "Brain macrophages" and "amoeboid microglial cells" are considered to belong to the class of exudate macrophages derived from blood monocytes. Thus, elements of hematogenous origin do exist in the intact brain parenchyma of neonatal rats and in lesioned brains of adult rats. The relationship between brain macrophages and resting microglial cells is discussed.

Animals↗

PubMed1992

Projections from fetal neocortical transplants placed in the frontal neocortex of newborn rats. A Phaseolus vulgaris-leucoagglutinin tracing study.

Fetal rat neocortex grafted into lesion cavities made in the newborn rat neocortex can exchange multiple axonal connections with the host brain. Most previous studies demonstrating efferent transplant-to-host brain connections have used fluorescent retrograde tracers injected into the host brain (Castro et al. 1985, 1987; Floeter and Jones 1984; O'Leary and Stanfield 1989). Other studies have used anterograde axonal tracing with either tritium-labelled amino acids impregnating the transplant and its efferents (Floeter and Jones 1985) or horseradish peroxidase injected into the transplants (Chang et al. 1984, 1986). In the present study we used the anterograde axonal tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) to examine in detail the course and termination of the efferent neocortical graft fibers. Twenty-six newborn rats had the right frontal cortex forepaw area removed by vacuum aspiration, while anesthetized by hypothermia. A piece of fetal frontal cortex 14-16 embryonic days old (E14-16) was immediately thereafter placed in the lesion, and the recipient rats allowed to survive for 5-7 months. At this time the rats were reoperated under sodium pentobarbital (Nembutal) anesthesia and the transplants iontophoretically injected with PHA-L. Two weeks later the animals were again anesthetized, perfused, and processed for PHA-L immunocytochemistry and routine histology. Analysis of acetylcholinesterase- (AChE) and Nissl-stained sections showed graft survival in 19 of the 26 animals used in this study. When these 19 brains were processed for PHA-L immunocytochemistry, 5 of them were found with certainty to have the PHA-L injection confined to the transplant. Based on these cases PHA-L-reactive fibers arising from labelled transplant neurons were traced into the ipsilateral host neocortex adjacent to the transplant and found to project through the subcortical white matter to the ipsilateral parietal neocortical area 1, and claustrum. Callosal fibers were traced to the contralateral frontal neocortical forelimb and parietal areas. Transplant fibers were also observed to descend through the caudate putamen in the dispersed fiber bundles of the internal capsule to distribute as terminal branches and varicose fibers within the mesencephalic periaqueductal gray, red nucleus, deep mesencephalic nucleus, and intermediate gray of the superior colliculus, as well as in the pontine gray. Similar fibers and terminations were present in the caudate putamen, the reticular, ventrobasal, centrolateral, posterior, and parafascicular thalamic nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholinesterase↗

PubMed1984

Regulation of cerebello-cortical transmission in the rat ventromedial thalamic nucleus.

On the basis of antidromic stimulation we have identified two distinct neuronal populations in the rat ventromedial thalamic nucleus. The largest population (96%) are thalamo-cortical relay cells which project via the internal capsule to the cerebral cortex. The smaller population of cells (4%) project caudally to the reticular formation and superior colliculus. These two cell types could be distinguished further on the basis of their patterns of spontaneous discharge. Relay cells fluctuate between two activity patterns (i) a rhythmic pattern characterized by periods of high-frequency bursting, and (ii) a more tonic discharge pattern of single spikes. The caudally projecting cells had a characteristic fast, regular type of spontaneous firing. Brachium conjunctivum stimulation evokes two distinct responses in thalamic relay cells. (i) a short-latency single spike, (ii) a longer latency, rhythmic response of 2-3 spikes. Both excitatory responses are followed by a period of cell quiescence. The type of response is dependent upon the cell's firing pattern. The short-latency response occurs during tonic, single-spike activity whilst the longer latency response occurs during high-frequency bursting activity. The short-latency response can be altered to the long latency response by increasing the level of anaesthesia or by applying a conditioning shock to known inhibitory pathways. Conversely the long latency response can be altered to the short-latency response by decreasing anaesthesia or by stimulation of the reticular formation. It is argued that both response types are evoked monosynaptically by activation of the same cerebello-thalamic fibres but that different ionic conductances which are active at different levels of membrane polarization are responsible for the two response patterns. Efficient time-locked cerebello-thalamo-cortical transmission occurs only during tonic single-spike activity, when cerebellar stimulation evokes a short-latency response. Such transmission is allowed or disallowed by the fine balance between converging excitatory and inhibitory afferents. In addition to a monosynaptic excitatory input from the cerebellar nuclei, relay cells received converging synaptic inputs from the substantia nigra, cerebral cortex, reticular formation and superior colliculus. Due to the anatomical arrangement in the rat it proved impossible to assess the role of the pallidum. The population of caudally projecting cells also received several converging synaptic inputs, but unlike those influencing relay cells, these inputs were all excitatory.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1985

Corticostriate projections from area 6 in the raccoon.

Corticostriate projections from area 6 in the raccoon were studied using the autoradiographic tracing method. Following injections of tritiated amino acids into two different cytoarchitectonic subdivisions of area 6, widespread and dense anterograde label was found in both the ipsilateral and contralateral caudate nucleus and putamen. The densest label was located adjacent to the internal capsule in the lateral part of the head of the caudate nucleus. This bilateral projection pattern from area 6 to the caudate nucleus and putamen is consistent with the hypothesis that the neostriatum maintains a close anatomical and functional relationship with area 6.

Animals↗

PubMed1975

The mode of synaptic linkage in the cerebro-ponto-cerebellar pathway of the cat. I. Responses in the brachium pontis.

Cerebrally-induced responses of pontine nuclei cells (PN cells) were studied in cats anesthetized with pentobarbitone sodium and with the midbrain transected bilaterally sparing only the cerebral penuncles. After stimulating the subcortical white matter, the internal capsule or the cerebral peduncle, mass potentials were recorded from the cut end of fibres in the brachium pontis (BP) and in the pyramid at the level of the trapezoid body. These potentials were regarded as indicating, respectively, the size of an output volley of PN cells and the size of its causative input volley through the pyramidal tract. BP responses consisted of short- and long-latency potentials which were caused by fast and slow conducting pyramidal tract volleys, respectively. The input-output relations for fast component responses took a characteristic S-shaped form resembling those obtained from the monosynaptic spinal reflex. The input-output relations for slow component responses were almost linear. Both fast and slow BP responses were remarkably potentiated after single or relatively brief repetitive peduncular stimulation, but were depressed after long-lasting high-frequency activation. During repetitive stimulation with varied frequencies, fast and slow BP responses showed different patterns of frequency-dependence of their amplitudes. These results suggest the existence of two separate transmission lines with different properties in cerebro-ponto-cerebellar pathways.

Animals↗

PubMed1979

Immunocytochemical identification of vasopressinergic and oxytocinergic neurons in the hypothalamus of the cat.

Our immunocytochemical investigation of the magnocellular neuroendocrine cells in the cat hypothalamus reveals a mixture of vasopressin (VP)- and oxytocin (OT)-containing neurons in the supraoptic (NSO), the paraventricular (NPV) and in five accessory nuclei (NAC). We describe the lateral hypothalamic nucleus (NLH), a new accessory nucleus, lying at the junction of the internal capsule and pallidum, and possibly involved in drinking behavior. Previously characterized incompletely in mammals, the four other accessory nuclei consist of the circularis (NC), anterior fornical (NAF), posterior fornical (NPF) and retrochiasmatic (NRC). The two peptidergic cell types, VP and OT, are equally mixed in the NPV and the NAC, but in the NSO VP neurons predominate. The perikarya of these VP and OT neurons do not show distinct morphological differences at the level of light microscopy. The organization of magnocellular neuroscretory neurons in the cat hypothalamus closely resembles that described in other mammals with the exception of the unique presence of the lateral hypothalamic accessory nucleus.

Animals↗

PubMed1980

Distribution of the largest neuron in mouse caudate-putamen nucleus: its position in large-cell--medium-cell clusters.

The position of the largest striatal neuron within territories delimited by medium-sized clustered neurons was charted in Nissl-stained sections through the mouse caudate-putamen nucleus. Medium-sized neuron somata occur in close proximity to this large cell at some point in the anteroposterior, mediolateral or dorsoventral extent of its soma. The size of the network of medium-sized neurons associated with the large cell may vary from two to 15 neurons. Even when this network is extensive, the large neuron is never completely surrounded. Most often, this cell also borders a fascicle of internal capsule fibers, and the entire cellular island may be aligned either parallel to or perpendicular to the orientation of these fibers. These findings suggest the hypothesis that cellular territories in the caudate-putamen nucleus have a very specific orientation in three dimensional space.

Animals↗

PubMed1981

Neocortical cholinergic innervation: a description of extrinsic and intrinsic components in the rat.

Electrothermic lesion of the peri-pallidal region of the rat caused a marked reduction in the activity of choline acetyltransferase in the ipsilateral fronto-parietal cortex without affecting the activity of glutamate decarboxylase. Only lesions that involved the ventral globus pallidus significantly reduced cortical choline acetyltransferase activity; and lesions limited to the thalamus, internal capsule, pyriform cortex or zone incerta were ineffective. Excito-toxin lesions of the ventral globus pallidus caused 45-5% reductions in all presynaptic markers for cholinergic neurons but did not significantly decrease presynaptic markers for noradrenergic, serotonergic or histaminergic neurons in the cortex. The maximal reductions in cortical choline acetyltransferase activity achieved with the pallidal lesion was 70%; and enzyme activity reached its nadir by four days after placement of the lesion. The pallidal lesion, which ablated the large isodendritic acetylcholinesterase positive neuronal perikarya, resulted in a profound loss in histochemically stained acetylcholinesterase-reactive fibers in the fronto-parietal cortex but not in the cingulate, pyriform and occipital cortex or hippocampal formation; analysis of the subregions in choline acetyltransferase activity. The kainate lesion of the parietal cortex to ablate intrinsic neurons did not reduce the activity of tyrosine hydroxylase, a marker for noradrenergic terminals, but depressed glutamate decarboxylase by 68%; in contrast choline acetyltransferase activity fell only 29%. The results indicate that approximately 70% of the cholinergic innervation in the fronto-parietal cortex is derived from acetylcholinesterase positive neurons in the peripallidal nucleus basalis, whereas the remainder appears to be localized in cortical intrinsic neurons.

Acetylcholinesterase↗

PubMed1979

An electrophysiological study of thalamo-caudate neurones in the cat.

Thalamo-caudate projection neurones were identified in cats by antidromic activation from the caudate nucleus, under chloralose anaesthesia or in cerveau isolé preparations. Units in nuclei centralis lateralis, medialis dorsalis, and centrum medianum-parafascicularis responded antidromically to one or more electrodes of a caudate nucleus array at latencies ranging from 0.4 to 16 ms. The responses did not appear to result from stimulus spread to the internal capsule. A separate population of medial thalamic units responded postsynaptically to caudate stimulation, at modal latency exceeding modal antidromic latency by 2 ms. Comparison of apparent conduction velocities for each thalamic nucleus indicated that the postsynaptic responses were activated by collaterals of thalamo-caudate neurones. A proportion of thalamo-caudate neurones responded to somatic stimulation; some of these were inhibited by caudate stimulation, and a few discharged on substantia nigra stimulation. These results demonstrate the possibility of somatic afferent and nigrofugal inputs to the caudate nucleus mediated by neurones of the medial thalamus.

Animals↗

PubMed1979

The cingular vocalization pathway in the squirrel monkey.

In 39 squirrel monkeys (Saimiri sciureus), the effects of various brain lesions on vocalizations elicited from the precallosal cingulate gyrus were tested. It was found that lesions abolishing the "cingular vocalization" completely can be traced from the stimulation site continuously down to the laryngeal motoneurons in the nucleus ambiguus. The pathway thus determined (Fig. 4) travels from the precallosal cingulate gyrus through the frontal white matter and enters the internal capsule from a dorsolateral position. The pathway then follows this structure in a medio-caudal direction down to the caudal diencephalon. Here, the effective lesions leave the corticospinal tract and ascend dorsally into the periaqueductal grey. The pathway follows this structure to its end where it sweeps lateral through the parabrachial area and then descends through the lateral pons and ventrolateral medulla to the nucleus ambiguus. In nine of the animals, in addition, the effects of bilateral anterior cingular lesions on vocalizations elicited in other brain areas were tested. It was found that the only vocalization-eliciting area which becomes ineffective after destruction of the anterior cingulate gyrus is the postero-medial orbital cortex.

Animals↗