Subcortical Brain Areas Research Articles

Middle cerebral artery thrombosis: acute blood-brain barrier consequences.

The effect of middle cerebral artery (MCA) thrombosis on the integrity of the blood-brain barrier (BBB) was studied in rats using horseradish peroxidase (HRP). Endothelial injury with subsequent platelet thrombosis was produced by means of a rose bengal-sensitized photochemical reaction, facilitated by irradiating the right proximal MCA segment with the focused beam of an argon laser. At 15 minutes following thrombosis formation, diffuse leakage of HRP was observed bilaterally within cortical and subcortical brain areas. Peroxidase extravasation was most dense within the territory of the occluded artery including neocortical areas and dorso-lateral striatum. Contralaterally, a similar distribution was observed but with less intense HRP leakage. Ultrastructural studies demonstrated an increase in permeability to HRP within arterioles, venules and capillaries. At these sites, the vascular endothelium contained HRP-filled pinocytotic vesicles and tubular profiles. Although less intense, bilateral HRP leakage was also observed following MCA stenosis or femoral artery occlusion. Endothelial-platelet interactions at the site of vascular injury may be responsible for releasing substances or neurohumoral factors which contribute to the acute opening of the BBB.

Cholinergic deficit in Alzheimer's disease: a study based on CSF and autopsy data.

Cholinesterase (ChE) activity was measured as a possible marker of cholinergic neurotransmission of the brain in CSF of 93 patients with probable Alzheimer's disease/senile dementia of the Alzheimer type (AD/SDAT) and of 29 control patients. ChE activity in CSF was decreased significantly in the AD/SDAT patients as compared to the controls. This reduction correlated significantly with the various measures of the severity of dementia. However, the reduction of ChE activity was only moderate (25-30%) even in patients with the most severe dementia and nonsignificant in patients with early symptoms of AD/SDAT. The significance of various confounding factors, which may interfere with CSF ChE measurements is discussed. Our findings seem to indicate that the deficiency of cholinergic neurons is not directly reflected in CSF and that the measurements of ChE activities in CSF are not helpful in diagnosing AD/SDAT. In the autopsy study the activities of cholineacetyltransferase (ChAT) and ChE were determined for ten brain areas of 20 AD/SDAT patients and of 14 controls. In AD/SDAT patients ChAT activity was profoundly decreased (50-85% decrease) in the cortical areas and hippocampus, but was unchanged or only mildly reduced in other subcortical brain areas. This study further confirms that the affection of cholinergic neurons is limited to projections from nucleus basalis to cortex and hippocampus, whereas other cholinergic neurons, like in striatum, seem to be relatively spared. In general, the activities of ChAT and ChE were lower in Alzheimer patients dying at younger age suggesting more severe disease process with these patients.

Brain irradiation: effects on regional MAO and COMT activity in the brain of the squirrel monkey and on the incorporation of [14C]tyrosine into catecholamines.

The effects of brain irradiation on the enzyme activity of monoamine oxidase (MAO) and catecholamine O-methyltransferase (COMT), as well as on the rate of incorporation of [14C]tyrosine into catecholamines (CAs), were examined in brain regions of the squirrel monkey (Saimiri sciureus). Results indicated that proton irradiation of the striate visual cortex at either 10,000 or 20,000 rad drastically affected the MAO activity, moderately affected the COMT activity, and significantly altered the incorporation of [14C]tyrosine into CAs in several brain regions. After 10,000 rad, MAO activity was increased in caudate nucleus (by 135%) and cerebellum (by 41%); significantly decreased in putamen (by 49%), gray matter (by 19%), and hippocampus (by 18%); and unchanged in brainstem. After 20,000 rad, MAO activity was markedly increased in caudate nucleus (by 114%), but decreased in cerebellum (by 24%), putamen (by 38%), gray matter (by 30%), and hippocampus (by 36%), and unchanged in brainstem. After 10,000 rad, COMT activity was significantly decreased in putamen (by 27%) and brainstem (28%). After 20,000 rad, COMT activity was significantly decreased in putamen (by 22%) and cortical gray matter (by 37%) but unchanged in the other brain regions examined. The 10,000 rad significantly increased the rate of incorporation of [14C]tyrosine into CAs in both the cerebellum (by 68%) and hypothalamus (by 26%), but 20,000 rad increased the rate only in hypothalamus (by 17%) and decreased the rate in hippocampus (by 24%). The whole-brain weights were significantly decreased after both 10,000 or 20,000 rad, by 17% and 11%, respectively. The only significant change in regional tissue weight was observed in putamen after 20,000 rad (a decrease by 17%). The protein concentration was significantly increased in hippocampus at both 10,000 (by 13%) and 20,000 (by 30%) but not affected in other brain regions examined. These data support our previous conclusion that a sustained chemical change occurs at the irradiated site and that the effect was transmitted to nonirradiated brain regions. Results also suggest that catecholaminergic pathways may exist between striate visual cortex and other cortical or subcortical brain areas where chemical changes were observed after visual cortical lesion by proton irradiation at various doses.

Intraocular development and adrenergic innervation of cortical and subcortical brain areas: influence of thyroid hormone deficiency.

Various immature brain regions have been isolated by grafting to the anterior chamber of the eye of adult recipients. The role of thyroid hormones for the growth of these isolated brain areas as well as their morphological maturation and adrenergic innervation in the eye have been investigated by surgical thyroidectomy of adult recipients prior to the intraocular brain grafting. Cortex cerebri showed a donor stage correlated thyroid hormone dependency so that 18-day donor fetuses gave rise to larger cortex grafts, whereas full-term donor fetuses resulted in smaller cortex grafts in thyroidectomized hosts. Brain stem showed an overall enhanced intraocular growth in thyroidectomized recipients, whereas both cerebellum and hippocampus did not seem to be influenced in oculo by a thyroid hormone deficiency. The morphological maturation of cortex cerebri grafts showed no alterations in thyroidectomized hosts as judged from light microscopy and cresyl violet staining. The density of sympathetic adrenergic nerves innervating the cortex cerebri grafts from the host iris was reduced by 50% in thyroidectomized hosts. This was parallelled by a reduction in noradrenaline concentration in cortex cerebri grafts in the experimental groups. Thus, the reduced number of nerves visible with Falck-Hillarp histochemistry in cortex cerebri grafts during thyroid hormone deficiency probably corresponds to a true reduction in adrenergic innervation. The present report points to a number of regionally as well as temporally selective effects on brain maturation and neuronal interaction of severe thyroid hormone deficiency.

5-HT concentration in cat's brain

Endogenous concentrations of TRP, 5-HT and 5-HIAA were determined in the different cortical and subcortical areas of adult cat's brain, using ion-exchange chromatography and spectrofluorimetric methods. Tryptophan is homogeneously distributed in all structures of the brain. 5-HT is mainly accumulated in the brain stem, hypothalamus and caudate nucleus, but also in cortical areas as olfactory and piriform gyrus. The ratio 5-HIAA/5-HT shows that 5-HT utilization is higher in the structures containing small amounts of 5-HT. Using the radioenzymatic assay described by Saavedra et al. (1973), the rostrocaudal distribution of 5-HT content was determined in olfactory and piriform cortex. Important concentrations of 5-HT were detected in the prepiriformis and anterior amygdaloidea areas. Using the same assay and microdissection on frozen frontal slices of the brain, the distribution of 5-HT concentration throughout the different layers of cortical areas was studied. Piriform, olfactory and sigmoid cortex present high concentrations in the superficial layers, including the molecular one. These results were confirmed by uptake studies, made on crude homogenates from frozen tissue, suggesting that 5-HT is mainly contained in the most external cortical terminals.

Noradrenaline distribution in subcortical areas of the human brain

Spectrofluorimetric assay of noradrenaline (NA) was performed in human postmortem brain material in an attempt to provide a detailed m ap of the subcortical distribution pattern of NA in the human brain. The concentration of NA was particularly high in 4 areas of the lower brain stem: the area postrema, the area of the nuclei paranigralis-parabrachialis pigmentosus, the locus coeruleus, and the interpeduncular nucleus. The NA-rich areas of the forebrain were determined to be the hypothalamus, the central amygdaloid nucleus, the nucleus accumbens septi, the medial, part of the olfactory area, and the bed nucleus of the stria terminalis. The biochemical mapping of NA is discussed in relation to distribution studies based on the histofluorescence technique.

Neurofibrillary changes neurofibrillary tangles in the subcortical areas of the aged brain, with special reference to their fine structure

60歳以上の老年者剖検脳100例について, 皮質下における神経原線維変化につき, 光顕および電顕的に検索した.1) 老人脳において, 神経原線維変化 (アルツハイマー原線維変化) は, 皮質のみならず皮質下にもみられた. その分布は被殻, 視床下部, 視床下核, 中脳 (中心灰白質, 動眼神経核, 縫線背核, 黒質), 橋 (橋核, 青斑核, 三叉神経核), 延髄 (舌下神経核, オリーブ核), 小脳歯状核などであった. 出現頻度はアンモン角55%に対して, 青斑核55%, 中脳中心灰白質 (動眼神経核も含む) 25%, 黒質6%の順であり, その他の部位では極めて少なかった. また皮質下のみに見出された例は5%で, 多くの例では皮質と同時にみとめられた. 加齢との相関は青斑核, 中脳中心灰白質でみとめられたが, その他の部位では種々であった.2) 皮質下にみられた神経原線維変化の微細構造は, 皮質と同じく直径220Åの細管構造で800Å毎にねじれを有する twisted tubules であった. 黒質に多数の原線維変化がみられ, 脱色素の著明な1例 (臨床的にはパーキンソニズム) のみ, ねじれのない直径150Åの細管構造を有する straight tubules であった. これは進行性核上性麻痺で報告されている神経原線維変化の微細構造と一致する.以上より, 老年者で大脳皮質下にみとめられた神経原線維変化は, その分布出現頻度, 微細構造より, アルツハイマー病, 老年痴呆にみられるものと一致し, 皮質のものと同一起源と考えられた. 主として皮質下に神経原線維変化の出現する進行性核上性麻痺とは, その分布および微細構造より区別されるが, その本質的な相関については尚検討を要する.

Δ9-tetrahydrocannabinol alters flow of blood to subcortical areas of the conscious rat brain

Δ 9-Tetrahydrocannabinol ( Δ 9THC), 1 mg/kg injected intravenously into conscious, unrestrained rats induced “cateleptoid” postures, vocalization, and in about half of the animals, a unique jumping behavior. During the period of cataleptoid behavior at 20 minutes after injection, the flows of blood to dorsal hippocampus, hypothalamus, cerebellum and basal ganglia were reduced significantly, whereas perfusion of cortical areas was unaffected. These regional changes in flow are believed to reflect acute functional responses to Δ 9THC.

Early albumin infusion to infants at risk for respiratory distress.

<h3>Abstract</h3> <h3>Objective</h3> The aim of this cross-sectional single center study was to investigate 18kDa translocator protein (TSPO)-PET as a biomarker for microglial activation in the 4-repeat tauopathies corticobasal degeneration and progressive supranuclear palsy (PSP). <h3>Methods</h3> Specific binding of the TSPO tracer ¹⁸F-GE-180 was determined by serial PET during pharmacological depletion of microglia in a 4-repeat tau mouse model. TSPO-PET was performed in 30 patients with corticobasal syndrome (CBS, 68±9 years, 16 female) and 14 patients with PSP (69±9 years, 8 female), and 13 control subjects (70±7 years, 7 female). Group comparisons and associations with parameters of disease progression and sTREM2 were assessed by region-based and voxel-wise analyses. <h3>Results</h3> Tracer binding was significantly reduced after pharmacological depletion of microglia in 4-repeat tau mice. Elevated TSPO labeling (standardized-uptake-value-ratios) was observed in subcortical brain areas of CBS and PSP patients when compared to controls, most pronounced in the globus pallidus internus (CBS: 1.039 [95%CI 1.000–1.078, p&lt;0.001], PSP: 1.046 [95%CI: 0.990–1.101, p&lt;0.001], controls: 0.861 [95%CI 0.802–0.921]), whereas only CBS patients showed additionally elevated tracer binding in motor and supplemental motor areas. TSPO labeling was only correlated weakly with parameters of disease progression in CBS and PSP but allowed sensitive detection of 4-repeat tauopathy patients. sTREM2 did not differ between patients with CBS and controls. <h3>Interpretation</h3> Our data indicate a potential of ¹⁸F-GE-180 PET to detect microglial activation in the brain of 4-repeat tauopathy patients, fitting to predilection sites of the phenotype. TSPO-PET may serve as a sensitive early disease stage biomarker in 4-repeat tauopathies.

Replacement of progesterone with a phenothiazine in the induction of maternal behavior in the ovariectomized nulliparous rat

Full maternal behavior is induced in the ovariectomized nulliparous rat when estrogen and prolactin are injected against a background of progesterone withdrawal. The hypothesis advanced was that progesterone at first elevates activation thresholds within the maternal mediating system and then, upon withdrawal, decreases these thresholds to levels lower than normal. It is during this presumed state of heightened neuronal excitability that estrogen and prolactin are pictured as being able to act on the mediating system to facilitate responsiveness to the sight, sound and odor of young. This hypothesis implies that an agent capable of effecting the kind of “rebound” attributed to the withdrawal of progesterone should substitute for progesterone in the induction of maternal behavior. Perphenazine, an amino derivative of chlorophenothiazine, was selected because of its demonstrated biphasic action on activity thresholds in cortical and subcortical brain areas. Used in place of progesterone in an injection schedule that included estrogen and prolactin, perphenazine was found as effective as progesterone in inducing maternal behavior. The data were held to support the hypothesis regarding the priming effect of progesterone-withdrawal on the maternal mediating system.

Electroencephalographic-behavioral dissociations during animal hypnosis

1. 1. Seventeen New Zealand White rabbits, with referential or bipolar electrodes in the motor cortex and various subcortical brain areas, were studied before and during hypnosis in 76 test sessions. 2. 2. Hypnosis was typically characterized by a reversible tonic immobility, relative unresponsiveness, decrease in muscle tone, and “arousal” EEG patterns. This state, although superficially similar to paradoxical sleep, was not the same, inasmuch as muscle tone was still present and there were no rapid eye movements, eyelid twitches, or phasic limb movements. 3. 3. After hypnosis was sustained for several minutes, a more “relaxed” state commonly occurred, wherein heart and respiratory rates decreased, muscle tone decreased further, and the EEG was of high voltage, slow activity. 4. 4. On 8 occasions in six rabbits, brief episodes of electrographic seizures occurred during hypnosis, without interrupting the tonic immobility. Seizures were induced in all rabbits with amphetamine, pentylenetetrazol, and the local anesthetic, dyclonine. Whether the drugs were injected before or during hypnosis, the motor component of the seizures was abolished by hypnosis, yet epileptiform EEG activity persisted during the apparent behavioral “sedation”. 5. 5. The “arousal” EEG, and especially the electrographic seizures, represented a conspicuous example of EEG-behavioral dissociation. Other similar dissociations have been reported in recent years, the best known of which are seen with paradoxical sleep, high doses of reserpine, certain neurological disorders, and physostigmine injection into chlorpromazine-sedated animals. 6. 6. The functional disconnection of motor activity in these states have common mechanisms. The existence of these several dissociation states emphasizes the limitations of current knowledge and the need for better understanding of sensori-motor interrelations.

Neuropharmacological profile of the young chick

The EEG and behavioral effects of diverse centrally active pharmacological agents were studied in unrestrained, unanesthetized, 5–14 day old white Leghorn cockerels. Effective doses of the barbiturates, alpha chloralose, chlorpromazine, reserpine, and morphine, produced behavioral depression and associated slow wave EEG activity. The hallucinogenic compounds, lysergic acid diethylamide, psilocybin, harmine, and mescaline, induced behavioral excitation, EEG arousal activity and abnormal body postures; the initial effects were often followed by behavioral depression. Caffeine produced no apparent alteration of either the EEG or the behavior of the young chick. Atropine induced an EEG arousal pattern, locomotor ataxia, and later a perceptible increase in normal motor activities. Amphetamine produced desynchronized EEG patterns characteristic of arousal, increased vocal activity, abnormal postures, and increased locomotor activities. Drug interactions with the unique amphetamine chick response revealed that atropine was the most effective amphetamine potentiating agent examined; while diphenhydramine and related agents were the most effective blocking agents of amphetamine induced behavior, that by themselves did not produce behavioral depression. Subconvulsant doses of metrazol produced slow wave EEG activity and behavioral quiescence; while convulsant doses induced clonus and diffuse, high voltage, spiking waves in the EEG. Strychnine produced tonic convulsions while the EEG demonstrated only a desynchronized pattern and not a pattern of spikes. The few differences in drug responses between avian and mammalian species appeared to be related to the absence of an avian functional cerebral cortex and a neothalamo-cortical anatomical complex. These anatomical differences in the bird result in: the absence of myoclonic jerking following alpha chloralose; the apparent lack of a caffeine stimulatory effect; the association of the atropine-induced EEG and behavioral effects; and the absence of strychnine-induced spikes in the cerebral hemisphere EEG. The many similarities in responsiveness between avian and mammalian species were more striking than the few differences. Especially prominent was the demonstration that the chick responses to those agents that effect mechanisms underlying the states of wakefulness and sleep, i.e. the barbiturates, chlorpromazine, reserpine, and amphetamine, were comparable to the responses reported for mammalian species. This suggested that there are a number of fundamental central nervous system mechanisms controlling EEG and behavioral activities, and originating in subcortical brain areas that appear to share common properties and presence in the homeothermal vertebrates.

Changes of aspartic acid in various cerebral structures of hibernating and aroused ground squirrels.

AbstractThe concentrations of aspartic acid in various regions of the brain of European ground squirrels (Cilellus citellus), sacrificed at different stages of the hibernating cycle, have been estimated by means of two dimensional paper chromatography. On the basis of experimental results obtained the following conclusions have been derived:1. Similar concentrations of aspartic acid where found in different cortical and subcortical areas of the ground squirrel brain.2. In hibernation at rectal temperatures of 5° C, an important decrease of aspartic acid was found in all the regions studied.3. Inversely, arousal from hibernation was associated with an increase of aspartic acid levels, atteining at 35° C the control values in a majority of investigated regions.The possible explanations and significance of the results obtained have been briefly discussed.

Cerebral localization: not where but in whom.

The individual and group reactions, learning techniques and capacities, and neurotic and drug-influenced behavior patterns of 64 cats and 49 monkeys were studied from 30 to 75 months before and after the implantation of lesions in 10 neo-, paleo- and sub-cortical brain areas. The data suggest that: 1. There are effects specific to each lesion despite inevitable variation in site, altered blood supply, etc. 2. There are a number of general changes common to lesions in several different areas. 3. The effects of any lesion are highly relatable to pre-operative characteristics and acquired patterns of behavior. 4. The effects are further dependent on the nature of post-operative treatment and experience.