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Noble gases are chemically inert elements, some of which exert biological activity. Experimental neuroprotection in particular has been widely shown for xenon, argon and helium. The underlying mechanisms of action are not yet fully understood. Besides an interference with neuronal ion-gated channels and cellular signaling pathways as well as anti-apoptotic effects, the modulation of neuroinflammation seems to play a crucial role. This review presents the current knowledge on neuroprotection by noble gases with a focus on interactions with the neuronal-glial network and neuroinflammation and the perspectives on clinical applications.

The neuropeptide calcitonin gene-related peptide (CGRP) is known to play a major role in the pathogenesis of pain syndromes, in particular migraine pain; however, its implication in inflammatory processes is not well known. The CGRP receptor antagonist BIBN4096BS was shown to reduce migraine pain and trigeminal neuronal activity. An analgesic action of this compound can also be found in rats with induced acute inflammation by injection of complete Freund's adjuvant (CFA) in one hindpaw. In this model the compound reduced inflammatory pain and spinal neuronal activity. Behavioral experiments (Randall-Selitto test) revealed a reversal of the CFA-induced mechanical hyperalgesia in rats after systemic drug administration. In vivo electrophysiological studies performed in rats injected with CFA using recordings of wide dynamic range neurons in deep dorsal horn layers of the lumbar spinal cord, confirmed a reduction of neuronal activity after systemic drug administration. The same considerable amount of reduction occurred after topical administration onto the paw with resulting systemic plasma concentrations in the low nanomolar range. Spinal administration of BIBN4096BS did not modify the neuronal activity in the CFA model which suggests that peripheral blockade of CGRP receptors by BIBN4096BS significantly alleviates inflammatory pain.

Many animal experiments have shown that anesthetics can have a neurotoxic effect on immature brains because they induce apoptosis and influence neurogenesis and synaptogenesis. In animal experiments this has substantial implications for the neurocognitive functions of animals in later life. Whether these results of animal experiments can be transferred to humans is currently the subject of intensive research. In several retrospective studies no clear association between anesthesia in premature babies, newborns or infants and the occurrence of learning disorders or behavioral problems could be found. The prospective studies GAS and PANDA are designed to obtain a deeper insight and if possible to clarify this problem. Because of the high relevance of this topic and in order to achieve more clarity for this problem when dealing with parents, the scientific working group for neuroanesthesia and pediatric anesthesia of the German Society for Anesthesiology and Intensive Care Medicine (DGAI) has formulated a position document on the basis of currently available data.

The intracellular pH (pHi) of neurons is tightly regulated, mainly by membrane-bound transporters acting as acid extruders or acid loaders. Regulation of pHi helps to control neuronal excitability, as increased bioelectric activity moderately lowers pHi and, in the sense of a negative feedback loop, intracellular acidosis mostly reduces neuronal excitability. Moreover, a change of pHi widely influences complex cellular functions. With respect to neuropsychopharmaca, little is known about whether or not they may affect neuronal H ( + )-homeostasis. To this aim, we tested several antipsychotics, antidepressants, anticonvulsants, and lithium for effects on neuronal pHi, using guinea pig hippocampal slice preparations in which CA 3 pyramidal neurons were loaded with the pHi-sensitive dye BCECF-AM. All antipsychotics, most antidepressants and about half of the anticonvulsants tested so far elicited reversible changes of neuronal pHi when applied at therapeutic and supratherapeutic concentrations. Although these results await confirmatory in vivo experiments, we believe that the pHi activity of neuropsychopharmaca needs further attention, especially when therapeutic mechanisms or even harmful side effects are discussed., (© Georg Thieme Verlag KG Stuttgart · New York.)

Atrophy, the wasting or shrinkage of tissue, of the nervous system is the main feature of neurodegeneration, i.e. the umbrella term for the progressive loss of structure or function of neurons. Loss of neurons due to cell death and axonal degeneration characterize neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease or amyotrophic lateral sclerosis. In these illnesses, it still has to be elucidated to which extent inflammation is part of the pathology. Conversely, in chronic inflammation of the central nervous system (CNS), atrophy has previously also been described and neurodegeneration is discussed as a pathologic feature. The most frequent chronic inflammatory disease of the CNS is multiple sclerosis (MS), which leads to devastating relapsing-remitting symptoms and disability during the relapses, increasingly during the course of disease in patients. Meanwhile it became clear that axons already reveal pathology early in the disease and neurons are affected in the cortex and the spinal cord, albeit to a different extent. The broadening of understanding neurodegenerative aspects of MS pathology demands and creates new therapeutic strategies. Current medication used in MS treatment as well as medications about to be approved are primarily anti-inflammatory therapies. By modulating the immune system and thereby blocking key steps of the pathology, the immunomodulation therapies in MS have a slight impact on disability progression. There is, however, clinical and experimental data concerning the potential neuroprotective properties of novel therapies. Combining anti-inflammatory and direct neuroprotective or even neuroregenerative therapy strategies would be a step forward in the treatment of multiple sclerosis.

To control the breathing rhythm the medullary respiratory network generates periodic salvo activities for inspiration, post-inspiration and expiration. These are under permanent modulatory control by serotonergic neurons of the raphe which governs the degree of phosphorylation of the inhibitory glycine receptor α3. The specific activation of serotonin receptor type 1A (5-HTR(1A)), which is strongly expressed in the respiratory neurons, functions via inhibition of adenylate cyclase and the resulting reduction of the intracellular cAMP level and a gradual dephosphorylation of the glycine receptor type α3 (GlyRα3). This 5-HTR(1A)-GlyRα3 signal pathway is independent of the µ-opioidergic transduction pathway and via a synaptic inhibition caused by an increase in GlyRα3 stimulates a disinhibition of some target neurons not only from excitatory but also from inhibitory neurons. Our physiological investigations show that this 5-HTR(1A)-GlyRα3 modulation allows treatment of respiratory depression due to opioids without affecting the desired analgesic effects of opioids. The molecular mechanism presented here opens new pharmacological possibilities to treat opioid-induced respiratory depression and respiratory disorders due to disturbed inhibitory synaptic transmission, such as hyperekplexia.

Cortical spreading depression (CSD) is a transient (60-120 s) and at 3-5 mm/min propagating depolarization wave of cortical neurons and glial cells and is characterized by a DC shift of 20-35 mV. It is accompanied by massive redistribution of ions between extracellular and intracellular compartments and by a water influx into the cells. Extracellular potassium ion concentration increases up to 60 mM/l. Potassium ions and the excitatory neurotransmitter glutamate essentially contribute to the initiation and propagation of CSD. Both depolarization and disturbance of brain ion homeostasis regenerate within a few minutes while enhancing energy metabolism, but do not cause damage to normally perfused brain tissue. The similar propagation velocity of CSD and visual scotoma during migraine aura led to the assumption that CSD could be the underlying mechanism of migraine aura. The observation of CSD waves in migraine aura patients with the magnet encephalogram (MEG) technique confirmed this theory. Although many data support the relationship between CSD and aura phase in migraine, the role of CSD in migraine headache is still disputed.

Regarding toxicity and efficacy tests of pharmacological and chemical substances (REACH legislation in Europe), there is a strong need to develop alternative methods for animal in vivo studies, in particular for human in vitro models. Here we present results from early phases of projects exploring the potential of embryonic stem cell models, with a special emphasis on embryo toxicity and neuronal stress.We have been able to demonstrate key functional read-outs of neural hESC models, in addition to representing mechanistic aspects which are characteristic for ischemia or excitotoxicity. There is agreement that these mechanisms underlie a variety of human neurodegenerative diseases. We discuss the possibilities to develop more precise endpoints on the molecular level and present an example of a protein biomarker signature emerging from a European FP6 project about embryo toxicity (www.reprotect.eu), employing murine and human embryonic stem cell models.

In this article recent advances in research on the pathogenesis of multiple sclerosis (MS) are summarized. New evidence from molecular histopathology is discussed focussing on neurodegenerative aspects. In addition findings with a direct effect on therapeutic decisions are presented which have contributed to improved immunotherapy. During the last decade important advances in immunotherapy have proven especially useful for patients with relapsing-remitting MS. Escalating algorithms are available for both relapses and long-term immunotherapy. Novel therapeutic approaches with monoclonal antibodies have increasing importance, yet side effects are not completely understood. The pathogenetic insights presented here may open new avenues for novel immunotherapies and lead to individualized MS therapy in the future. Limitations are given for primary progressive MS due to the lack of suitable tissue specimens and experimental models. Neuroprotective treatment strategies aiming at the protection of glial and neuronal cells are still in early stages of development.

Statins, i.e. HMG-CoA reductase inhibitors, reduce the risk of stroke and may have therapeutic potential for other neurologic diseases, including multiple sclerosis and Alzheimer's disease. In addition to lowering cholesterol levels, statins exert a number of cholesterol-independent (pleiotropic) effects. While endothelial, anti-thrombotic, anti-inflammatory, and immunomodulatory, i.e. peripheral, effects of statins are well known, little is known about the direct effects on neurons. This may be of clinical relevance because some statins are able to cross the blood-brain barrier. Recent experimental studies demonstrate that statins reduce the activity of neuronal glutamate receptors and protect neurons from excitotoxic insults. At higher doses, however, statins may also inhibit neurite sprouting and even induce neuronal apoptosis.

Clinically used anesthetics show amnestic, sedative, hypnotic and immobilizing properties. On a molecular level these drugs affect several receptors in the cell membrane of neurons. By using genetically engineered mice a linkage can now be made between actions on certain receptors and clinically desired and undesired effects. Experiments show that a certain GABA(A) receptor subtype mediates hypnosis and immobility, whereas another subtype is involved in side-effects like sedation and hypothermia. These findings form the basis for the development of new drugs, acting highly specific and with fewer side-effects.

Transcranial magnetic stimulation as mapping method offers the possibility to measure aspects of motor cortex excitability painlessly and non-invasively. Using this neurophysiological tool, new insights into the effects of central-acting drugs are possible. Particularly striking seems to be the potential of this approach to gain new insights into neurobiological processes associated with neuropsychiatric diseases like schizophrenia or major depression. In combination with genetic aspects, TMS is able to bridge the gap between molecular research and clinical approach.

Post-mortem investigations have confirmed that glutamatergic NMDA, AMPA, and kainate receptors are involved in the pathophysiology of schizophrenia. It is still unclear, however, whether the altered number of receptors is caused by the disease itself or the medication. Therefore, animal models were investigated for effects of antipsychotic medication after treatment periods of up to 6 months, the results of which are summarized here. Generally, NMDA receptor binding was found to be increased in striatum and nucleus accumbens after therapy with haloperidol, whereas clozapine only increased the number of receptors in nucleus accumbens. While haloperidol led to an increase in AMPA receptors in the posterior cingulate gyrus, striatum, insular cortex, and n. accumbens, clozapine was found to elevate ligand binding in the anterior cingulate gyrus and infralimbic cortex. Although kainate receptor binding was increased in hippocampus by both antipsychotics, clozapine was significantly more effective. In conclusion, data reveal different effects from the typical neuroleptic haloperidol and the atypical antipsychotic clozapine. The results suggest that post-mortem findings in patients with schizophrenia may at least partially be explained by drug effects and plasticity changes induced by long-term medication with antipsychotics.

Neuronal injury following cardiac arrest (global cerebral ischaemia) and stroke (focal cerebral ischaemia) is one of the major causes of the high morbidity and mortality associated with these pathological events. One of the major characteristics of this kind of neuronal injury is delayed neuronal degeneration. An increasing body of evidence indicates that apoptosis (programmed cell death) is involved in this process after global and focal cerebral ischaemia. In contrast to necrosis, which is primarily characterised by cellular metabolism failure and loss of membrane integrity, apoptosis represents a pattern of cell death in which an active energy-dependent cell death programme is initiated without any concomitant inflammatory reaction. Based on the knowledge that apoptosis plays a major role in delayed neuronal death following cerebral ischaemia, a variety of new neuroprotective therapeutic strategies have emerged (e.g. caspase inhibitors, viral anti-apoptotic proteins, modulation of systemic anti- and pro-apoptotic protein expression and death receptor antagonists). Many of these are still being experimentally evaluated. Relevant anti-apoptotic and neuroprotective therapeutic strategies could be introduced into clinical practice in the near future. The field of anaesthesiology will benefit from these important developments. New therapeutic opportunities might also become available in emergency medicine and critical care medicine. This article reviews the molecular basis of apoptosis and its physiological and pathophysiological relevance. The mechanisms of delayed neuronal death following focal and global cerebral ischaemia are presented with particular emphasis on the role of apoptosis. Based on this, possible future therapeutic interventions are highlighted and discussed.

Positron emission tomography studies on volunteers showed that, at concentrations inducing the loss of consciousness, propofol, halothane and isoflurane reduce glucose metabolism of neocortical neurones by 20-50%. To find out whether these effects are caused by direct anaesthetic actions on cortical structures, experiments were carried out on isolated neocortical brain slices. In these investigations an excellent correlation was observed between anaesthetic concentrations causing a half-maximal depression of action potential firing in neocortical brain slices and anaesthetic blood concentrations monitored during awaking from anaesthesia in humans. Furthermore, it could be shown that, at concentrations approximately one half the MAC-value, isoflurane decreases the frequency of auditory evoked 30-40 Hz oscillations in the neocortex by 50%. Similar quantitative effects were observed on spontaneously occurring high frequency rhythms in neocortical brain slices. However, not all aspects of cerebral anaesthetic actions can be explained by direct effects on cortical neurones. The EEG synchronisation and the amplitude reduction of mid latency auditory evoked potentials are probably related to the inhibition of thalamic neurones. Halothane, isoflurane, enflurane and propofol reduced action potential firing of cortical neurones by enhancing GABAA receptor-mediated synaptic inhibition. This molecular mechanism seems also to be involved in depressing painful stimuli-induced motor responses. Nevertheless, there must be a difference between relevant anaesthetic mechanisms on the cerebral and spinal level. This follows from the observation that the relation between the concentration causing the loss of consciousness and the concentration that depresses movements considerably varies among different anaesthetic agents.

The spectrum of action of flupirtine includes analgesic, muscle-relaxant and neuroprotective properties. The substance's mechanism of action has yet to be fully explained. Over the past few years, however, evidence has accumulated that flupirtine interacts with the glutamatergic N-Methyl-D-Aspartate (NMDA) receptor. Although it was not possible to demonstrate a direct effect on the NMDA receptor, all of the findings pointed to an indirect influence on the NMDA receptor in the sense of a functional NMDA antagonism. It was thus postulated that a site of action "up- or downstream" of the NMDA receptor is influenced. Such a site of action proved to be the G-protein-activated inwardly rectifying K+ channels (GIRK), the opening of which leads to a stabilization of the resting membrane potential of neuronal cells and thus causes an indirect inhibition of the NMDA receptor. At therapeutically relevant concentrations, flupirtine is a neuronal potassium channel opener. This mechanism may explain the spectrum of action of flupirtine. Selective neuronal potassium channel opening (SNEPCO) thus proves to be a new principle of action, making flupirtine the prototype of a new substance class with analgesic, muscle-relaxant and neuroprotective properties. The experimental basis for this working hypothesis and the resulting model concepts are presented from the perspective of a four-stage approach.

Signal transfer between neurons and between neurons and muscle cells is mediated by the secretion of neurotransmitters. The axon of the presynaptic cell contains synaptic vesicles, the storage organelles for neurotransmitters. Arrival of an action potential causes calcium-influx into the axon and leads to fusion of synaptic vesicles with the presynaptic plasma membrane. Recently, the events between calcium-influx and membrane fusion were elucidated on a molecular level. The family of SNARE-proteins was identified as the key players in neurosecretion. They are located on synaptic vesicles (VAMP) or on the presynaptic plasma membrane (syntaxin, SNAP-25). Intimate protein-protein interactions between the SNARE-proteins are responsible for the attachment and merger of vesicle and the plasma membrane. Fusion is triggered by calcium-binding to synaptotagmin, another protein recently identified on synaptic vesicles. The molecular mechanism of the action of clostridial neurotoxins was also elucidated. Botulinum-as well as Tetanus toxins are proteases which cleave neuronal SNARE-proteins. This explains the long known inhibition of neurosecretion caused by these toxins. The proteolytic action of Tetanus- and Botulinum toxin occurs in different types of neurons, resulting in a stimulatory or inhibitory effect on muscle cells. This selective degradation of SNAREs explains the opposing clinical signs of tetanus (cramps) and botulismus (paralysis).

Introduction: There is no data available on the action of etomidate on ion currents in human neuronal cells. Therefore the effects of etomidate on a human neuronal delayed rectifier potassium current were investigated., Method: Outward rectifying potassium currents of human neuroblastoma SH-SY5Y cells were measured using the whole cell patch-clamp technique. Cells were grown in RPMI-medium (+Pen/Strep and FCS) at 37 degrees C and 5% CO2. The holding potential was -80 mV. Potassium currents were evoked by depolarizing the membrane potential to values from -50 mV to +90 mV in 10 mV steps using an EPC-7 patch-clamp amplifier (List medical electronics) and pclamp version 5.71 (Axon instruments)., Results: Etomidate differentially inhibited steady-state and peak potassium current with IC50-values of 170 microM for peak current suppression and 120 microM for steady-state current respectively. Etomidate induced inactivation-like behaviour of the potassium current and changed the voltage dependence of potassium current activation., Conclusion: The results demonstrate that etomidate has more than one effect on the potassium current, indicating the complexity of general anaesthetic actions on neuronal targets. The actions of etomidate on human neuronal potassium currents may potentially contribute to the myocloni observed with this general anaesthetic agent during induction of anaesthesia.

Treating ischemic stroke we could compare a (control-)group of 318 patients under up to date hemodilution therapy to a group of 100 patients receiving exactly the same treating scheme but including an add-on administering of Cerebrolysin. It proved a statistically validated better outcome within the Cerebrolysin add-on treated group evaluated by the Barolin-Neuro-Rehabilitation Scale. 1) More effect on social and occupational parameters than on motor functions, but also including some of those. 2) Cerebrolysin accelerates recovery and therewith offers better starting points for rehabilitation. As stroke is one of the main social-medical neuro-rehabilitation and gerontological problems of our days these results should be recognized in a general therapeutical use.

The authors deal with the heuristic value of the "neurobiological model of alcohol dependence". It allows the study of the influence of a defined noxe on different brain structures. Additionally, it enables the quantification of regeneration and restitution processes in abstinence. Because of this, the alcoholism model goes beyond dementia, the model which has dominated brain research so far. Neuropathological studies in humans and animals found a reduction in the volume of white matter and a partial degeneration, or even loss of specific neurons. According to animal data, this could to a certain extent be genetically determined. Alcohol exerts a distinct influence on different neurotransmitter systems. This research will deepen our understanding of the neurotoxic and psychotropic properties of alcohol, and of the development of dependence. Little is known about the role of astrocytes in the reaction of the brain to alcohol. Here again, the neurobiological model of alcohol dependence could be of value in learning more about their interactions with neurons. Using Magnetic Resonance Imaging and CAT-scans, the decrease in volume of white and grey matter was demonstrated in vivo. The degree and the time course of brain damage seems to be influenced less by drinking history than by age and gender. There is evidence that female alcoholics develop brain damage more readily than men. When abstinent, an increase in the volume of white and grey matter can be observed. This is not due to the rehydration of brain tissue alone. Future research will need to deal with the question of whether the central nervous system is capable of partial regeneration. For the study of neuroplasticity, the neurobiological model of alcohol dependence seems to be particularly well suited.

Apart from adrenergic and cholinergic neurones, peptidergic neurones are involved in the autonomic control of nasal mucosa. Their transmitter substances are peptides, so-called "neuropeptides". It is assumed that they are released from peptidergic neurones in the nasal mucosa after irritation of receptors by unspecific stimuli, and are responsible for the symptoms of hyperreactive rhinopathy. Repeated topical application of Capsaicin (8-methyl-N-vanillyl-6-nonenamide) leads to a selective degeneration of peptidergic neurones and desensitisation of its receptors in the nasal mucosa. 123 patients who were suffering from hyperreactive rhinopathy were treated in a prospective study by repeated topical applications of capsaicin solutions in increasing concentrations. A symptom score demonstrated an improvement of the predominating symptoms (nasal congestion, hypersecretion, sneezing) by 62% to 72%. A reduction of unpleasant side effects following application (epiphora, itching, sneezing, mucosal oedema) indicating a desensitising effect could be documented by a symptom score and by active anterior rhinomanometry. Immunohistochemical investigations of nasal mucosa biopsies revealed no reduction of peptidergic neurones within the nasal mucosa, so that a blockage of receptors seems to be responsible for the positive effects. The treatment of hyperreactive rhinopathy with capsaicin or related substances seems to be a promising new way in the treatment of hyperreactive rhinopathy. Further investigations have to prove the site of effect and mechanism of activity of the substance, such as the best modality of application.

In recent years, much interest has focused on NMDA- and opiate-receptor-mediated actions of ketamine, whereas the search for other potential neuronal effects of this phencyclidine derivative has not attracted comparable attention. Nevertheless, the superfamily of voltage-operated membrane channels (VOC), ligand-operated ion channels (LOC) stimulated by acetylcholine and GABA, the non-NMDA subtypes of glutamate-activated LOC (kainate and AMPA receptor channels) and the closely related re-uptake processes of the monoamines noradrenaline, dopamine and serotonin should be considered potential targets of ketamine within the nervous system. Therefore, this review article summarizes our current knowledge of ketamine effects on these transmembrane ion channels and carrier mechanisms in the neuron. Unlike the NMDA-insensitive glutamate receptors for kainate and AMPA, the LOC activated by acetylcholine and the principal inhibitory amino acid GABA (gamma-aminobutyric acid) were both sensitive to clinical concentrations of ketamine, although in different ways. The relevance of these findings for the generation of the anaesthetic state, however, still remains to be established. Moreover, all VOC tested so far were reversibly inhibited at supra-clinical concentrations of ketamine (> 100 microM). Whereas no direct relevance to the state of general anaesthesia emerges from these data, local anaesthesia produced by comparably high concentrations of ketamine can be explained on the basis of its more or less unspecific inhibitory actions on VOC. Finally, the excellent antinociceptive activity of ketamine at the spinal and supra-spinal level may result at least in part from its inhibitory effects on the neuronal uptake of the monoamines noradrenaline, dopamine and serotonin.

Owing to a lack of knowledge of the pathophysiology and pathochemistry of Parkinson's disease, conservative treatment was long restricted to the treatment of symptoms. In recent decades, as the role of dopamine became better known, progressive improvements in therapy were achieved, which initially meant the administration of the precursor, L-Dopa, of the primarily non-replaceable neurotransmitter, and later augmentation of the activity of dopamine in addition. Amantadine, a highly effective drug with a wide spectrum of action and a high level of tolerability, was successfully introduced in 1969. The recently discovered NMDA antagonism, also in conjunction with a description of the mechanism of action of amantadine, which makes it possible to inhibit the effect of excitatory amino acids--in particular glutamate--in the CNS, led to the principle of neuro-protection, which is now considered the key to the treatment of Parkinson's disease.

To the present day there is no consensus of opinion as to which molecular events lead to the complex clinical state generally referred to as anaesthesia. The multitude of simultaneous physiological changes are also responsible for this lack of consensus. During anaesthesia, for example, consciousness, perception, memory, pain, and muscle relaxation are altered. The actions of anaesthetics correlate very well with their partitioning into lipophilic phases. Lipophilic interactions are non-specific. Therefore, it is likely that anaesthetics act at many different sites. Cell membranes are not the only possible sites but also membrane proteins and the various hydrophobic domains they contain. The multitude of clinical anaesthetic effects is paralleled by the complexity of molecular interactions. A better understanding of anaesthesia requires an integrated view of anaesthetic effects at the various systemic levels, beginning with the molecular domain and ending with the intact central nervous system. Anaesthesia research could be directed more towards man because it has now become possible to conduct molecular in-vitro studies with human cells as well as non-invasive studies of the intact human central nervous system.

In a controlled double blind experiment the influence of a continuous i.v. infusion of Nimodipine (1 microgram kg-1 min-1) upon infarct size, histopathology and neurological outcome in rats with permanent middle cerebral artery (MCA) occlusion was examined. The infusion was started 20 min. before the induction of ischemia and continued 4 hours thereafter. The nimodipine treated animals were subdivided into hypotensive (MABP lower than 85 mmHG for more than 5 minutes after arterial occlusion) and normotensive groups. Infarction size, documented by TTC, H&E and Nissl staining was significantly smaller (p less than 0.001) in nimodipine normtonic rats than the lesions in placebo and saline treated rats, as well as compared with hypotonic nimodipine animals (largest infarction). These differences were found to be entirely at the expense of the cortical (frontoparietal) component of the lesion, suggesting "penumbra" action of the drug. Moreover, nimodipine normotonic rats displayed lower cortical neuronal injury in the periinfarct zone. These findings were corroborated by corresponding better neurological scores. Our results indicate that nimodipine is effective in reducing focal cerebral ischemia, provided the MABP is maintained higher than 85 mmHg.

By December 1988 reports on 525 ARC- (AIDS-Related Complex) and AIDS-patients with neurological or neuropsychological signs treated with Zidovudine (AZT = 3'-Azido-2,3'Dideoxythymidine) had been published in literature. In 204 (38.8%) cases of HIV infection a temporary improvement in the neurological deficits was reported. Peripheral and central neurological side-effects were observed in 124 (23.6%) patients.

The proatriopeptins consisting of 126 amino acids is formed and stored by the myocytes of the atria. In its disintegration among others develops the alpha-atriopeptins consisting of 28 amino acids, which in normal blood pressure and blood volume, respectively, is secreted only in small quantities. The content of alpha-atriopeptins in the plasma varies approximately between 4 and 12 pmol/l in the course of 24 hours, the half-life period amounts to 1 to 2 min. In an increase of the blood pressure in the atria and in tachycardia the output of alpha-atriopeptins increases. It is bound to receptors of the cells of the glomerular zone, the vessels, the hypothalamus and the kidneys and activates a guanylate cyclase. The main effects of the alpha-atriopeptins are an inhibition of the secretion of aldosterone, vasopressin and renin, a dilation of the arteries, an increase of the glomerular filtration as well as an increase of the sodium and water excretion. In certain diseases of the kidneys and the heart the content of alpha-atriopeptins in the plasma increases.

Effects of Aminobenzoic Acid Derivatives on the Ionic Currents in Myelinated Nerve/1st Communication: Dose-response curves Derivatives of aminobenzoic acid were modified and their blocking potencies on the ionic currents of single potential clamped myelinated nerve fibres were tested by means of dose-response curves. Starting from metacaine (ethyl m-aminobenzoate), derivatives of different basicity were produced by N-dimethylization, N-quarternization and by preparing a corresponding aliphatic amine. The corresponding free acids and the structural isomers of metacaine were tested as well. The physico-chemical properties of the derivatives were characterized by their pKa-values and their octanol/water partition coefficients. Our findings suggest that the site of action of the aminobenzoic acids tested is located at the inside of the nerve membrane. Moreover, no indications of binding to a receptor in a pharmacological sense were found.

A single subcutaneous injection of monosodium-L-glutamate induces severe ultrastructural alterations in certain AChE positive parenchymal cells of the Area postrema of the adult rat. Signs of cellular degeneration include massive intracellular edema, swelling of mitochondria, vacuolization of the cisternae of the rough endoplasmic reticulum and marked alterations in the chromatin pattern of the nucleus. Identification of these cells as neurons is based on the presence of axosomatic synapses.

The neostriatum of adult rats was investigated by means of the Golgi rapid impregnation procedure following surgical (unilateral stereotaxic MFB lesions or complete deafferentation) and pharmacological (i.p. application of pargyline, amphetamine, reserpine, haloperidol in submaximal doses) pretreatments, respectively. The neurons of this brain area--as a whole, ten types can be differentiated according to morphological criteria--do exhibit a characteristic impregnation behavior being in proportion to the mode of pretreatment in each case. The impregnation behavior of the neurons is postulated to depend on the polarization state of their membranes which may be explained in pharmacological and physiological terms.

Layer V-pyramidal neurons of the temporal neocortex of albino rat (24 and 36 days old) were examined morphometricly. Length and width of the perikaryon, long and short diameter of the nucleus and the position of the nucleus in the perikaryon were compared with each other after three fixations (Formalin, Bouin, Carnoy). Changes of form and/or position caused by fixation allow no exact statements about the condition in vivo. They are founded on the changes on molecular plain. Resultant problems for karyometric investigations are pointed out.

In 80 Wistar rats were investigated the prolonged action of Angiotensin II in a dosage of 0,05 mg/kg/die ip. appl. on microstructures of the sensomotoric cortex. It is observed, after the first application, a biphasic reaction of brain vessels, in the beginning a pronounced vasodilatation (5 min p.-inject) which 10 min later turn into a vasoconstriction. In correlation with the applications frequency the repeated injection of the octapeptide leads to perivascular edemas. Neurons of the sensomotoric cortex show strong swellings, which later turn in to involutions. Pronounced destructions of mitochondria are demonstrable. Conceivable mechanisms were discussed.

The Locus coeruleus (LC) of the adult rat was investigated by means of fluorescence histochemical and rapid GOLGI impregantion technique. The majority of LC neurons displayed, as a result of application of the FALCK-HILLARP-technique and the LOREN-technique, resp, the well-known fluorescence typical of catecholamine neurons. There was lack of fluorescence within a minor portion of cells. Fluorescence histochemically, serotoninergic afferents could be shown to go up to noradrenaline-containing neurons in some cases. In the GOLGI material, 3 types of neurons could be distinguished: Polygonal neurons exhibiting somatic spines, fusiform neurons, and small-sized spine-less neurons. Based on morphological features, the polygonal neuron type is considered to represent the monoamine-containing neurons of the Locus coeruleus. It appears uncertain at present to attribute the fusiform and small spineless neuron types in a functional manner. functional implications inherent that morphological heterogeneity have been discussed.

In metabolic tests in narcotized rats it could be demonstrated that isoprenaline under continuous intramuscular infusion is, calorigenically, about three times more effective than noradrenalin. By blocking the uptake of sympathomimetics into peripheral adrenergic neurones by means of desipramine the calorigenic effect of noradrenalin is increased thirteenfold while under isoprenaline it decreases slightly.

Neurons of the Wistar-rats' occipital cortex were morphologically investigated after chronical application of amphetamine. The nerve cells impregnated according to the Golgi-Kopsch technique showed in part changes on both the dendrites and in the axonal region. Besides a partial reduction of spines and of peripheral dendritic arborizations round varicosities of different density could be observed on the dendrites and on the axon, either, which were discussed to be due to a neurotoxic effect of amphetamine.