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C Nitsch

Publications and source records attributed to C Nitsch.

At least 55 records · Page 3Linked to original sources
PubMed1986

Distant blood-brain barrier opening in subfields of the rat hippocampus after intrastriatal injections of kainic acid but not ibotenic acid.

Blood-brain barrier (BBB) permeability towards proteins was determined in rats 4 h after intrastriatal kainic or ibotenic acid application, using Evans blue as indicator. Whereas, with the exception of the unspecific damage in cortex, after ibotenic acid BBB remained intact in deep brain areas. Evans blue leakage was found ipsilateral to the kainic acid injection, occasionally in striatum, thalamus and amygdala and regularly in hippocampus. There it was confined to the fimbria and the CA3 field. Only rarely a mirror focus-like staining was present in the contralateral hippocampus. The ultrastructural investigation revealed that BBB opening in CA3 is due to increased transendothelial pinocytosis; the tight junctions were intact. Thus, changes in the microenvironment around vessels, elicited by kainic acid and/or seizures, might be responsible for BBB opening.

Animals↗
PubMed1986

Pathophysiological aspects of blood-brain barrier permeability in epileptic seizures.

Blood-brain barrier (BBB) permeability to macromolecules was assessed during seizures induced by pentylenetetrazole, bicuculline, methoxypyridoxine, methionine sulfoximine, and kainic acid. It was observed that each convulsant induced a specific pattern of regional BBB opening. This was, however, only the case when systemic blood pressure (BP) rose with seizure onset. The analysis of regional cerebral blood flow revealed that a high increase in flow in rabbits with BP rise is related to the normal flow at rest in the single brain region, but not to BBB permeability. In rabbits without BP increase, regional flow increase was low but well modulated and is possibly a better indicator for neuronal activity. The ultrastructural analysis showed that macromolecular transport over the cerebrovascular endothelium is by pinocytosis, an neurotransmitter controlled process. It is suggested that seizure-induced regional BBB opening is determined by two factors: release of neurotransmitters due to the process of auto-regulation during peripheral pressure increase, and change in local neurotransmitter milieu due to the action of the convulsant and/or the seizure activity.

Animals↗
PubMed1986

The blood-brain barrier to horseradish peroxidase at the onset of bicuculline-induced seizures in hypothalamus, pallidum, hippocampus, and other selected regions of the rabbit.

Rabbits were subjected to bicuculline-induced generalized seizures of 15-min duration to elucidate the mechanism by which the macromolecule horseradish peroxidase (HRP) traverses the blood-brain barrier (BBB) in specific brain areas. Transendothelial pinocytosis at the level of arterioles was the main route of passage. In addition, in thalamus and hippocampus pinocytotic vesicles were observed in capillaries. In thalamus, hypothalamus and septum vesicles in the endothelium of venules were also present. Repeatedly, pinocytotic vesicles were ejecting their content into the interendothelial clefts, so that the presence of HRP reaction product between adjacent tight junctions cannot be considered a conclusive evidence for their opening. The HRP, which had reached the neuropil due to the seizure-evoked BBB opening, accumulated in the interstitial spaces and penetrated the synaptic cleft. Uptake of the tracer in vesicular form into presynaptic boutons, presumably excitatory ones as diagnosed by their ultrastructural features, was observed in all brain regions. The uptake was rare in septum, periaqueductal gray, hypothalamus, and cerebellar cortex; frequent in pallidum, hippocampus, and medulla oblongata; and very intense in thalamus. Uptake in postsynaptic dendrites was present mostly in the vicinity of boutons. Incorporation into glial processes was rare and confined to perivascular astrocytes. It is suggested, that HRP traverses the BBB by regionally selective, transmitter-controlled pinocytotic transport and that the neuronal uptake of the foreign protein is at least partially dependent on the involvement of synapses of particular brain regions in the paroxysmal activity during the generalized seizures.

Animals↗
PubMed1986

Carcinogenesis and the central nervous system.

Wistar rats were injected with the carcinogen 3-MC. The effect of psychoactive drugs on tumor-bearing rats was examined with respect to tumor growth, survival time, and remissions. CNS drugs were given both prophylactically and therapeutically. Psychopharmaceuticals like piracetam and pyrithioxin as well as catecholamine-agonists like imipramine had a definite antineoplastic effect. This effect was increased when combined with other CNS drugs and, in particular, the combination of piracetam with chemotherapeutic agents resulted in a high rate of remission and reduced the toxicity of chemotherapy. Surgical removal of tumors and subsequent treatment with CNS drugs led to a high rate of cure without metastasis. After tumor appearance, we found cerebral neuropathological changes as described in the paraneoplastic syndrome. The EEGs of 3-MC-injected rats showed early pathognomic changes in frequency and amplitude. Similar changes were found in animals with transplantation tumors (Walker carcinoma and Jensen sarcoma). The EEG pattern was normalized after surgical removal of Jensen sarcoma and treatment with piracetam and pyrithioxin. These EEG changes might have occurred as a result of transmitter metabolism; ie, carcinogenesis of both induced tumors and transplanted tumors was accompanied by an increase of GABA content in hypothalamus and hippocampus and a reduced concentration of monoamines or their metabolites in hypothalamus and caudate nucleus. Long-term treatment with piracetam or imipramine again arrested all these changes. More recently, we achieved good results with the combination of CNS drugs and cAMP agonists. We therefore conclude that carcinogenesis interferes with the metabolism or availability of cyclic nucleotides and transmitters that regulate their level. CNS drugs may effect a new balance resulting in tumor suppression.

Animals↗
PubMed1985

Incongruence of regional cerebral blood flow increase and blood-brain barrier opening in rabbits at the onset of seizures induced by bicuculline, methoxypyridoxine, and kainic acid.

Cerebral blood flow (CBF) was estimated using [3H]nicotine as tracer in 18 discrete rabbit brain regions at the onset of generalized seizures induced by bicuculline (BC), methoxypyridoxine (MP), and kainic acid (KA) and compared with the previously described regional pattern of blood-brain barrier (BBB) opening. Regional CBF increased 3- to 5-fold in BC-seizures, 2- to 3-fold (except in inferior colliculus) in MP-seizures, and twofold (no change in inferior colliculus) and periaqueductal gray) in KA-seizures. In general, CBF elevation was greater in areas with a high original CBF, and below average in regions with a low control value. However, under each condition a few areas did not follow this rule, viz. the occipital cortex and the basal part of the cerebellar vermis with low flow values in BC-seizures, the inferior colliculus with no change and the pallidum with a relatively high flow during MP-seizures, and limbic system areas with an exceptionally high flow during KA-seizures. The usual rise in arterial blood pressure (BP) at the onset of the seizure, necessary for the development of a BBB lesion, was absent in a few animals with BC- and MP-seizures, yet, their CBF was elevated in most regions although to a lesser extent. No relationship appeared to exist between the rise in CBF and the regional pattern of BBB opening. It is concluded that a loss of cerebral autoregulation is a prerequisite for BBB leakage, but the location of the opening is determined by neuronally derived factors which differ from convulsant to convulsant and from brain region to brain region.

Animals↗
PubMed1984

Specific gravity increases and brain water content decreases during short epileptiform seizures in discrete rabbit brain areas.

In rabbits subjected to bicuculline (BC)- or pentylenetetrazole (PTZ)-seizures of 3 or 20 min duration or to adrenaline-induced hypertension, specific gravity (SG) was measured bilaterally in 15 regional brain areas in order to detect possible associations between the regionally limited blood-brain barrier openings due to these insults (see Nitsch and Klatzo 1983) and the presence of brain edema. In controls, a large variation between regional SG levels became evident: between 1.0467 in cerebellum and 1.0417 in preoptic area. A seizure duration of only 3 min was not sufficient to change SG significantly. After 20 min of seizures independent from the inducing agent, SG increased in all brain areas. The degree of increase seemed to be unrelated to presence or absence of a blood-brain barrier opening. In an attempt to avoid the influence of blood impregnation on the SG value, blood was replaced by saline before measurement. In controls, saline perfusion decreased SG only in the two areas with the highest original levels, thus documenting the partial dependency of the regional SG on the hematisation of the tissue. After 20 min of PTZ-induced seizures, SG in saline-perfused rabbits increased, but no longer significantly in all brain areas. This suggests that a part of the seizure-induced SG increase can be attributed to the hyperemia of the brain during the convulsions. On the other hand, an increase in flow volume due to hypertension did not change SG with the exception of the septum, preoptic area and hypothalamus. The direct measurement of water content with the classical wet/dry method in 4 gross brain areas showed that early seizure periods are in fact associated with a dehydration of the brain. This phenomenon could be explained by a glucose- and lactate-induced rise in blood osmolarity which in turn might cause a dehydration of the brain tissue.

Animals↗
PubMed1984

Regional changes in cerebral blood flow and blood-brain barrier permeability during epileptiform seizures and in acute hypertension in rabbits.

Interrelationship between the breakdown of the blood-brain barrier (BBB) to Evans blue and elevations in the regional cerebral blood flow (rCBF) was studied in rabbits subjected to adrenaline- or metaraminol-induced systemic hypertension and also in bicuculline-induced seizures. The rCBF was assessed in small samples from various regions of the brain with the use of [3H]nicotine, and the permeability of the BBB was evaluated with an Evans blue tracer. In acute hypertension, Evans blue extravasations were observed in the occipital cortex and sometimes in the superior colliculus, i.e., the regions which also showed the highest elevations in rCBF. The breakdown of the BBB in acute hypertension was clearly related to the rate of mean arterial blood pressure rise, being much less pronounced in the metaraminol group, which showed a much slower blood pressure elevation rate. In bicuculline-induced seizures, there was no evident correlation between the amplitude of rCBF elevations and Evans blue extravasations. Preservation of BBB integrity was observed in areas showing high elevations in the rCBF.

Acute Disease↗
PubMed1984

Effects of frontal motor cortex ablation on the ultrastructure of cat substantia nigra.

3,4 and 5 days after the removal by suction of the left motor and premotor cortex in cats, the presence of ultrastructural changes in the substantia nigra was investigated. Whereas after 3 days dark bouton degeneration was rare, after 4- and 5-day survival it was regularly found for a distinct type of synapse containing in its bouton densely packed small round vesicles and possessing an asymmetric synaptic junction with a dendrite. Often these darkly degenerated boutons contained dense bodies which were also observed in the same type of synapse not yet exhibiting a dark axoplasm. Various inclusions, especially glycogen depots, were present in these boutons suggesting that they were in the process of degeneration. The glial reaction was comparatively severe. In addition, darkly shrunken dendrites contacted both, by intact and by altered boutons were frequently encountered as well as single degenerated neuronal perikarya. The nature of this effect, i.e. whether transneuronal or retrograde, could not be clarified. All these alterations were found bilaterally after the unilateral cortex ablation, and were confined to the substantia nigra pars compacta along its whole anterior-posterior extent. In the pars reticulata, solely traversing myelinated axons in the process of degeneration were observed. Thus, the results are in agreement with the older studies and with evidence from primates demonstrating that the substantia nigra receives a bilateral projection from the motor and premotor cortex.

Animals↗
PubMed1984

Immunocytochemical demonstration of the GABA-ergic neurons in rat globus pallidus and nucleus entopeduncularis and their GABA-ergic innervation.

GAD (E.C. 4.1.1.15), the endogenous biosynthetic marker enzyme for GABA, was localized in rat globus pallidus and nucleus entopeduncularis (pallidum) by peroxidase-antiperoxidase immunocytochemistry. In the two nuclei we observed numerous GAD-like immunoreactive boutons containing large pleomorphic vesicles. These boutons formed axodendritic and axosomatic synaptic contacts mostly of the symmetric type. Following colchicine injection near the border of globus pallidus or nucleus entopeduncularis, the vast majority of both larger and smaller neurons exhibited GAD immunoreactivity and were contacted by numerous GAD-immunoreactive boutons. These data demonstrate that pallidal neurons are of predominately GABA-ergic nature and receive an extensive GABA-ergic input. Thus, the globus pallidus and the nucleus entopeduncularis major output stations of the basal ganglia may represent sites of extensive GABA-mediated inhibition of GABA-ergic inhibitory neurons.

Animals↗
PubMed1983

Regional patterns of blood-brain barrier breakdown during epileptiform seizures induced by various convulsive agents.

In unrestrained rabbits with generalized epileptic seizures induced by systemic application of convulsant drugs, regional changes in blood-brain barrier (BBB) permeability to macromolecules were investigated using Evans Blue (EB) as indicator. BBB leakage due to seizures was present only in animals in which the mean arterial blood pressure rose about 50 mm Hg with the onset of convulsive motor activity. However, a blood pressure increase was not necessarily associated with the occurrence of BBB opening. Pentylenetetrazole-induced seizures resulted in bilateral EB leakage mainly in the hypothalamus, with exception of the mammillary bodies, and the preoptic area, and they were associated, in most cases, with an intensive staining of the cerebellum and also of the midbrain tegmentum. In contrast, seizures due to the GABA receptor blocker bicuculline brought about a penetration of the dye in the region of the pallidum, whereas the GABA synthesis inhibitor methoxypyridoxine produced BBB breakdown in the hippocampus. Methionine-sulfoximine convulsions resulted in a selective stain of the corpora mammillaria, and kainic acid induced a diffuse leakage in neocortical brain areas. As a rule, BBB breakdown was bilateral and confined to anatomically limited brain areas, suggesting that BBB integrity was not only disturbed by abrupt increases in the intraluminal pressure, but was also influenced from the brain tissue. The fluorescence microscopic observations revealed that the tracer penetrated into the neuropil through larger vessels. It had the tendency to accumulate in neurons. In case of the hippocampus, CA2 pyramidal cells revealed more intense uptake of EB than those of the adjacent fields.

Animals↗
PubMed1983

Alterations in the content of amino acid neurotransmitters before the onset and during the course of methoxypyridoxine-induced seizures in individual rabbit brain regions.

In rabbits, generalized seizures were induced by methoxypyridoxine, and changes in amino acid concentrations of 15 brain regions were investigated before seizure onset and during the course of sustained epileptiform activity. As previously reported, gamma-aminobutyric acid (GABA) concentration decreased preictally in most regions. At the same time, taurine level was elevated in the hypothalamus, thalamus, hippocampus, caudatum, and frontal cortex. After 90 min of seizures, it was significantly decreased in the hypothalamus, periaqueductal grey, substantia nigra, frontal cortex, and cerebellum. Glycine content was reduced preictally only in the substantia nigra; after seizure onset its concentration rose in all brain areas. Glutamate content in the frontal cortex decreased before seizure onset; after 1.5 h of seizures, its concentration in cerebellum, caudatum, and hippocampus was reduced. Aspartate level was decreased in most areas after sustained seizures; in putamen, however, it was elevated. In contrast, glutamine content increased preictally in the superior colliculus and in all brain areas by approximately 200% after 90 min of seizures. Alanine and valine content also rose markedly in most brain areas after prolonged seizures, and threonine showed the same tendency. The single brain regions were observed to respond to methoxypyridoxine in highly individualistic ways. For example, the glycine content of the substantia nigra, which is believed to utilize this amino acid as a neurotransmitter, decreased preictally. The potential importance of the superior colliculus in seizure induction is considered in view of the early rise in glutamine level. The antagonistic preictal behavior of taurine and GABA is discussed with respect to synthesis, uptake from the blood, and antiepileptic properties.

Amino Acids↗
PubMed1982

Increase in taurine content before onset of seizures induced by a glutamate decarboxylase inhibitor.

The concentration of taurine was measured in 15 brain regions of the rabbit before the onset of convulsions induced by the potent glutamate decarboxylase inhibitor methoxypyridoxine. A significant rise in taurine content was observed in the hippocampus, putamen, caudate nucleus, frontal cortex, thalamus and hypothalamus. GABA levels determined from the same tissue samples were all significantly reduced. An unaffected taurine synthesis coupled with blocked transport to the blood is considered as a possible explanation for this taurine increase.

Animals↗
PubMed1982

Effect of motor and premotor cortex ablation on concentrations of amino acids, monoamines, and acetylcholine and on the ultrastructure in rat striatum. A confirmation of glutamate as the specific cortico-striatal transmitter.

At 1, 2, and 4 weeks after unilateral premotor and motor cortex ablation in rats, a significant and lasting decrease in glutamate levels in the ipsilateral versus contralateral striatum was observed. A significant corresponding fall in aspartate was seen only after 1 week. In contrast, there was a large increase in the striatal concentrations of lysine, threonine, alanine, and glutamine 1 week after the cortical ablation. This correlates with the extensive glial proliferation in the deafferented ipsilateral striatum. Four weeks after cortical ablation the GABA concentration was significantly increased. There was no decrease in other putative transmitters (dopamine, serotonin, acetylcholine, glycine and taurine), nor was a glutamate decrease observed in the hippocampus or in the hypothalamus, which do not receive direct premotor and motor cortical inputs. Both biochemical and morphological evidence for a minor contralateral cortico-striatal projection was obtained. Correlating with the fall in glutamate, ultrastructural observations indicated the degeneration of two types of striatal synapses, i.e., those of the axo-spinous type III and of the axo-dendritic type VII. Frontal cortex ablation clearly affects, in opposite directions, the metabolism of various striatal amino acids but not that of acetylcholine and the monoamine transmitters. The results strongly support the view that glutamate is the transmitter of the cortico-striatal fibers.

Acetylcholine↗