bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin‐10 modulates neuronal threshold of vulnerability to ischaemic damage
Authors: Grilli Mariagrazia , Barbieri Ilaria , Basudev Harsha , Brusa Rossella , Casati Carlo , Lozza Gianluca , Ongini Ennio 
Published: March 2003

AbstractInterleukin‐10 (IL‐10) is a powerful suppressor of cellular immune responses, with a postulated role in brain inflammation. First, we have evaluated the role of this cytokine in ischaemic brain damage using IL‐10 knockout (IL‐10–/–) mice. The middle cerebral artery (MCA) was occluded in either IL‐10–/– or wild‐type animals of corresponding strain (C57Bl/6) and age. Infarct volume was assessed 24 h later in serial brain sections. Brain infarct produced by MCA occlusion was 30% larger in the IL‐10–/– than in wild‐type mice (21.8 ± 1.2 vs. 16.9 ± 1.0 mm3, respectively; P < 0.01; Student's t‐test). To further characterize these findings, studies were extended to in vitro models. Primary neuronal cortical cultures derived from IL‐10–/– animals were more susceptible to both excitotoxicity and combined oxygen–glucose deprivation compared with cell cultures from wild‐type mice. Moreover, when added to the culture medium, recombinant murine IL‐10 (0.1–100 ng/mL) exerted a concentration‐dependent prevention of neuronal damage induced by excitotoxicity in both cortical and cerebellar granule cell cultures taken from either strain. The accordance of in vivo and in vitro data allows us to suggest a potential neuroprotective role of IL‐10 against cerebral ischaemia when administered exogenously or made available from endogenous sources.
Role of desensitization of AMPA receptors on the neuronal viability and on the [Ca2+]i changes in cultured rat hippocampal neurons
Authors: Ambrósio António F. , Silva Ana P. , Malva João O. , Mesquita José F. , Carvalho Arsélio P. , Carvalho Caetana M. 
Published: March 2003

AbstractWe investigated the role of desensitization of α‐amino‐3‐hydroxy‐5‐methyl‐isoxazole‐4‐propionate (AMPA) receptors on the neurotoxicity and on the [Ca2+]i changes induced by kainate or by AMPA in cultured rat hippocampal neurons. The neuronal viability was evaluated either by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, or by analysis of cell morphology. Short‐term exposure of the neurons to kainate or AMPA (30 min) was not toxic, but the exposure for 24 h to the excitotoxic drugs caused a concentration‐dependent neurotoxic effect which was prevented by LY 303070, a noncompetitive AMPA receptor antagonist. In the presence of cyclothiazide (CTZ), kainate or AMPA was toxic (30 min exposure), or the toxic effect was significantly enhanced (24 h exposure), but in this case LY 303070 did not completely protect the cells against kainate‐induced toxicity. The alterations in the [Ca2+]i caused by kainate or AMPA showed a great cell‐to‐cell variability. LY 303070 completely or partially inhibited the responses stimulated by kainate. CTZ differentially affected the responses evoked by kainate or AMPA. In the majority of hippocampal neurons, CTZ did not potentiate, or only slightly potentiated, the kainate‐stimulated responses but in 11% of neurons there was a great potentiation. In AMPA‐stimulated neurons, the responses were slightly or greatly potentiated in the majority of neurons, but not in all of them. The results show that AMPA and kainate may be toxic, depending on the time of exposure and on the blockade of the desensitization of the AMPA receptors. Overall, our results clearly show that there exist different populations of hippocampal neurons with different sensitivities to kainate, AMPA, CTZ and LY 303070. Moreover, the effects of CTZ on both [Ca2+]i alterations and neurotoxicity are not fully correlated.
Glial cell line‐derived neurotrophic factor modulates ischemia‐induced tyrosine hydroxylase expression in rat hippocampus
Authors: Miyazaki Hiroyuki , Ono Takashi , Okuma Yasunobu , Nagashima Kazuo , Nomura Yasuyuki 
Published: March 2003

AbstractRecently, we have reported that glial cell line‐derived neurotrophic factor (GDNF), which supports the survival of dopaminergic neurons, prevents delayed neuronal death in the hippocampal CA1 region induced by transient forebrain ischemia. In the present study, we examined the role of GDNF in the expression of tyrosine hydroxylase (TH) mRNA induced by transient forebrain ischemia in rats. The expression of TH mRNA was increased in a time‐dependent manner, with a significant increase in 24 h to 7 days, in the hippocampus after induction of transient forebrain ischemia, as determined using the reverse transcription and polymerase chain reaction method. Although it has been suggested that the increase of dopamine β‐hydroxylase mRNA expression correlates with the activation of noradrenergic neurons, no increase of dopamine β‐hydroxylase mRNA in the hippocampus was observed in our system. Western blot analysis revealed that TH protein, but not dopamine β‐hydroxylase protein, was produced in a time‐dependent manner in the hippocampus during the ischemia. Interestingly, the induction level of TH mRNA was reduced by intrahippocampal microinjection of GDNF (1.0 μg), and this local GDNF treatment also reduced the increase of TH‐like immunohistochemistry‐positive terminals in the hippocampus. In contrast, local GDNF treatment of normal rats increased the TH mRNA expression at 6–12 h. These findings suggest that GDNF protects against neuronal degeneration including delayed neuronal death in the hippocampal CA1 region by modulating the expression levels of TH mRNA and protein.
Corticothalamic axons contact blood vessels as well as nerve cells in the thalamus
Authors: Feig Sherry L. , Guillery R. W. 
Published: March 2003

AbstractCorticothalamic axons in cats and rats were studied after labelling by intracortical injections of axonally transported markers. Individual axons were traced to their terminal branches. Many preterminal segments had a tightly spiral or winding course which was often closely adjacent to a thalamic blood vessel. Electron micrographs of such axons showed them lying immediately adjacent to the vascular basement membrane, without the astrocytic cytoplasm that generally separates neural processes from the basement membrane of vessels. The functional nature of this neurovascular relationship remains to be explored.
Synaptic interactions increase optic flow specificity
Authors: Horstmann Wolfram , Egelhaaf Martin , Warzecha Anne‐Kathrin 
Published: March 2003

AbstractRepresentations of optic flow are encoded in fly tangential neurons by pooling the signals of many retinotopically organized local motion‐sensitive inputs as well as of other tangential cells originating in the ipsi‐ and contralateral half of the brain. In the so called HSE cell, a neuron involved in optomotor course control, two contralateral input elements, the H1 and H2 cells, mediate distinct EPSPs. These EPSPs frequently elicit spike‐like depolarizations in the HSE cell. The synaptic transmission between the H2 and the HSE cell is analysed in detail and shown to be very reliable with respect to the amplitude and time‐course of the postsynaptic potential. As a consequence of its synaptic input, the HSE cell responds best to wide‐field motion, such as that generated on the eyes when the animal turns about its vertical body axis. It is shown that the specificity of the HSE cell for this type of optic flow is much enhanced if rapid membrane depolarizations, such as large‐amplitude EPSPs or spike‐like depolarizations, are taken into account rather than the average membrane potential.
The activity‐dependent plasticity of segmental and intersegmental synaptic connections in the lamprey spinal cord
Authors: Parker David , Grillner Sten 
Published: March 2003

AbstractActivity‐dependent synaptic plasticity has been proposed as a contributory factor in the patterning of rhythmic network activity. However, its role has not been examined in detail. Here, paired or triple intracellular recordings have been made from identified neurons in the lamprey locomotor network to examine the potential relevance of activity‐dependent synaptic plasticity in segmental and intersegmental spinal networks. Segmental inputs from glutamatergic excitatory interneurons (EIN) to ipsilateral glycinergic crossed caudal (CC) interneurons were facilitated or depressed during spike trains at 5–20 Hz. Connections between EINs were depressed. Glycinergic inputs from small ipsilateral inhibitory interneurons were depressed in motor neurons, but were facilitated in CC interneurons. Excitatory inputs from small crossing interneurons to motor neurons were depressed, whereas inhibitory inputs were unaffected. With the exception of connections between EINs, significant effects occurred with stimulation that mimicked interneuron spiking during network activity. Intersegmental EIN synaptic properties were also investigated. EIN inputs did not differ significantly when examined from zero to four segments rostral to motor neurons or CC interneurons. However, caudally located EINs evoked greater activity‐dependent facilitation than did rostral EINs. Whilst the amplitude or plasticity of EIN inputs in the rostral or mid‐trunk regions of the spinal cord did not differ, EINs in the caudal trunk region evoked greater facilitation. Synaptic transmission between locomotor network neurons thus exhibits activity‐dependent plasticity in response to physiologically relevant stimulation. Activity‐dependent plasticity could thus contribute to the patterning of the rhythmic network output.
Facial nerve injury‐induced disinhibition in the primary motor cortices of both hemispheres
Authors: Farkas Tamás , Perge János , Kis Zsolt , Wolff Joachim‐R. , Toldi József 
Published: March 2003

AbstractUnilateral facial nerve transection induces plastic reorganization of the somatotopic order in the primary motor cortex area (MI). This process is biphasic and starts with a transient disinhibition of connections between cortical areas in both hemispheres. Little is known about the underlying mechanisms. Here, cortical excitability has been studied by paired pulse electrical stimulation, applied either within the MI or peripherally to the trigeminal nerve, while the responses were recorded bilaterally in the MI. The ratios between the amplitudes of the second and first evoked potentials (EPs or fEPSPs) were taken as measures of the inhibitory capacity in the MI ipsilateral or contralateral to the nerve injury. A skin wound or unilateral facial nerve exposure immediately caused a transient facilitation, which was followed by a reset to some level of inhibition in the MI on both sides. After facial nerve transection, the first relatively mild reduction of inhibition started shortly (within 10 min) after denervation. This was followed by a second step, involving a stronger decrease in inhibition, 40–45 min later. Previous publications have proved that sensory nerve injury (deafferentation) induces disinhibition in corresponding areas of the sensory cortex. It is now demonstrated that sham operation and, to an even greater extent, unilateral transection of the purely motoric facial nerve (deefferentation), each induce extended disinhibition in the MIs on both sides.
Arm trajectory and representation of movement processing in motor cortical activity
Authors: Schwartz Andrew B. , Moran Daniel W. 
Published: March 2003

AbstractWe review experiments in which single‐cell primary motor cortical activity was recorded from Rhesus monkeys (Macaca mulatta) while they performed reaching and drawing tasks. The directional tuning curves generated during reaching were modulated by the speed of movement and this was reflected in the magnitude of population vectors calculated from firing rates of a large population of cells. Directional and speed representation in the firing rates of these cells is robust across both reaching and drawing. Several behavioural invariants related to the speed of drawing were represented in the time‐series of population vectors. This high fidelity neural representation of velocity found in motor cortex can be used to visualize the dynamics of motor cortical activity during drawing and suggests that the cost function governing the rate of drawing is bound by neural processing.
IAP family proteins delay motoneuron cell death in vivo
Authors: Perrelet D. , Ferri A. , MacKenzie A. E. , Smith G. M. , Korneluk R. G. , Liston P. , Sagot Y. , Terrado J. , Monnier D. , Kato A. C. 
Published: March 2003

AbstractNeuronal apoptosis inhibitory protein (NAIP), and human inhibitors of apoptosis 1 and 2 (HIAP1 and HIAP2) are three members of the mammalian family of antiapoptosis proteins called ‘inhibitors of apoptosis’ (IAP). These molecules can prevent apoptosis in vitro and the over‐expression of NAIP can decrease ischemic damage in the hippocampus. The goal of our experiments was to determine whether administration of NAIP, HIAP1 and HAIP2 could rescue motoneurons following axotomy of a peripheral nerve. In young rats, an adenoviral gene transfer technique was used to deliver and express these proteins in motoneurons; a fluorescent tracer was simultaneously added as a means for quantitatively assessing the rescue of fluorescently labelled motoneurons in serial sections of the lumbar spinal cord. Control experiments using adenoviral vectors (adv) expressing the lacZ gene showed that 14% of the sciatic motoneuron pool could be transfected indicating the existence of a subpopulation of spinal motoneurons susceptible to this class of viral vectors. The administration of an adv‐NAIP, adv‐HIAP1 and adv‐HIAP2 rescued 30–40% of motoneurons at one week after sciatic axotomy. The efficiency of these proteins was similar to that of two neurotrophic factors, ciliary neurotrophic factor and brain‐derived neurotrophic factor, administrated by the same viral technique. The effect of the IAP proteins on motoneuron survival decreased with time but was still present after 4 weeks postaxotomy; the duration of the response was dependent upon the viral titre. These experiments demonstrate that IAP family proteins can prevent motoneuron cell death in vivo and may offer a new therapeutic approach for motoneuron diseases.
Effects of glutamate agonist versus procaine microinjections into the basal forebrain cholinergic cell area upon gamma and theta EEG activity and sleep–wake state
Authors: Cape Edmund G. , Jones Barbara E. 
Published: March 2003

AbstractServing as the ventral, extra‐thalamic relay from the brainstem reticular activating system to the cerebral cortex, basal forebrain neurons, including importantly the cholinergic cells therein, are believed to play a significant role in eliciting and maintaining cortical activation during the states of waking and paradoxical sleep. The present study was undertaken in rats to examine the effects upon electroencephalogram (EEG) activity and sleep–wake state of inactivating basal forebrain neurons with microinjections of procaine versus activating them with microinjections of agonists of glutamate, which is the primary neurotransmitter of the brainstem reticular activating system. Microinjections into the basal forebrain were performed using a remotely controlled device in freely moving, naturally sleeping/waking rats during the day when they are asleep the majority of the time. Procaine produced a decrease in gamma (30–60 Hz) and theta (4–8 Hz) EEG activities, and an increase in delta (1–4 Hz) associated with a loss of paradoxical sleep, despite the persistence of slow wave sleep. α‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) and N‐methyl‐d‐aspartate (NMDA) produced an increase in gamma and a decrease in delta, while eliciting waking. In addition, NMDA, which has been shown in vitro to induce rhythmic bursting in the cholinergic cells, significantly increased theta activity. Following the microinjections of NMDA, c‐Fos protein, which has been shown to reflect neural activity, was found in numerous cholinergic, and also GABAergic (γ‐aminobutyric acid) and other non‐cholinergic neurons, in the substantia innominata and magnocellular preoptic nucleus near the microinjection cannulae. These results substantiate the role of cholinergic, possibly together with other, basal forebrain neurons in cortical activation, including elicitation of gamma and theta activities that underlie cortical arousal during waking and paradoxical sleep.
Electrophysiological properties of microglial cells in normal and pathologic rat brain slices
Authors: Boucsein Clemens , Kettenmann Helmut , Nolte Christiane 
Published: March 2003

AbstractMicroglial cells serve as pathologic sensors of the brain. They are highly abundant in all regions of the central nervous system (CNS) and are characterized by a ramified morphology within the normal tissue. In the present study, we have developed a procedure to study the membrane properties of identified, in situ microglia in acutely isolated brain slices from rat cortex, striatum and facial nucleus. Unlike the well characterized cultured microglial cells, ramified microglia of the slice are characterized by little, if any, voltage‐gated membrane currents and a very low membrane potential. They are thus distinct from neurons, other glial cells and nonbrain macrophages. To study the consequences of microglial activation on the membrane channel pattern, we compared cells in the normal facial nucleus and at defined times after facial nerve axotomy. Within 12 h of axotomy, microglial cells expressed a prominent inward rectifier current and thus acquired the physiological properties of cultured microglia. Within 24 h of the lesion, the cells expressed an additional outward current, which is typical for lipopolysaccharide (LPS)‐activated microglia in vitro. Seven days after the lesion, at a time of major regenerative processes in the facial nucleus, the physiological properties of microglial cells had reverted to those present prior to the pathological event. In conclusion: (i) ramified microglial cells represent a physiologically unique population of cells in the brain; (ii) are distinct from their cultured counterparts; and (iii), undergo a defined pattern of physiological states in the course of pathologic events.
Activation of spinal cannabinoid 1 receptors inhibits C‐fibre driven hyperexcitable neuronal responses and increases [35S]GTPγS binding in the dorsal horn of the spinal cord of noninflamed and inflamed rats
Authors: Drew L. J. , Harris J. , Millns P. J. , Kendall D. A. , Chapman V. 
Published: March 2003

AbstractThe analgesic potential of cannabinoid (CB) receptor agonists is of clinical interest. Improved understanding of the mechanisms of action of cannabinoids at sites involved in the modulation of acute and sustained inflammatory nociceptive transmission, such as the spinal cord, is essential. In vivo electrophysiology was used to compare the effect of the synthetic CB agonist, HU210, on acute transcutaneous electrical‐evoked responses of dorsal horn neurons of noninflamed anaesthetized rats and anaesthetized rats with a peripheral carrageenin inflammation. CB receptor G‐protein coupling in lumbar spinal cord sections of noninflamed and carrageenin‐inflamed rats was studied with in vitro autoradiography of guanylyl 5′‐[γ‐[35S]thio]triphosphate ([35S]GTPγS) binding. Spinal HU210 significantly inhibited the C‐fibre‐mediated late (300–800 ms) postdischarge response of dorsal horn neurons of noninflamed and carrageenin‐inflamed rats; the CB1 receptor antagonist SR141716A blocked the effect of HU210. HU210 had limited effects on A‐fibre‐evoked dorsal horn neuronal responses of both groups of rats. HU210 significantly increased [35S]GTPγS binding in the dorsal horn of the spinal cord of both groups of rats compared with basal [35S]GTPγS binding; SR141716A blocked these effects. The predominant effect of spinal HU210, via CB1 receptor activation, was on the C‐fibre driven postdischarge responses, a measure of neuronal hyperexcitability following repetitive C‐fibre stimulation. Sustained, but not enhanced, antinociceptive effects of HU210 following carrageenin inflammation are reported; CB receptor G‐protein coupling was not altered by inflammation. These results strengthen the body of evidence suggesting CB agonists may be an important novel analgesic approach for the treatment of sustained pain states.
Temporal integration vs. parallel processing: coping with the variability of neuronal messages in directional hearing of insects
Authors: Ronacher Bernhard , Krahe Rüdiger 
Published: March 2003

AbstractThe behaviour of many animals indicates a high precision in the processing of sensory signals, which often seems at odds with the large variability of individual neuronal responses. Using the directional hearing of the grasshopper Chorthippus biguttulus (Ch. biguttulus) as a model system, we investigated the possible contributions of temporal integration and parallel processing at the receptor level to the observed behavioural acuity. The precision of the animals' phonotactic orientation behaviour to stimuli of different durations was measured and compared with the spiking responses of auditory receptor cells, leading to the following results. A behavioural decision based on integrating the spikes from a pair of receptors (one cell in each ear) over a 1000‐ms time window would substantially decrease the error probability, compared with evaluating a 250‐ms period. The animal as a whole, however, responded as precisely to a 250 ms stimulus as to a stimulus of natural duration (c. 1000 ms). A phonotactic decision based on a 1.5 dB intensity difference between the ears corresponds to a spike count difference of approximately 1 spike per 100 ms in a pair of receptors. As these differences are in the order of the statistical spike count fluctuations, the error probabilities for an ideal observer of the spike count are substantially higher (13–18%) than the errors observed in the behavioural tests (only 5%). We conclude that the animals' nervous system has to sample information from a pool of 6–13 receptors to arrive at the observed behavioural precision.
Effects of barium on stimulus‐induced rises of [K+]o in human epileptic non‐sclerotic and sclerotic hippocampal area CA1
Authors: Kivi A. , Lehmann T. ‐N. , Kovács R. , Eilers A. , Jauch R. , Meencke H. J. , Von Deimling A. , Heinemann U. , Gabriel S. 
Published: March 2003

AbstractIn the hippocampus of patients with therapy‐refractory temporal lobe epilepsy, glial cells of area CA1 might be less able to take up potassium ions via barium‐sensitive inwardly rectifying and voltage‐independent potassium channels. Using ion‐selective microelectrodes we investigated the effects of barium on rises in [K+]o induced by repetitive alvear stimulation in slices from surgically removed hippocampi with and without Ammon's horn sclerosis (AHS and non‐AHS). In non‐AHS tissue, barium augmented rises in [K+]o by 147% and prolonged the half time of recovery by 90%. The barium effect was reversible, concentration dependent, and persisted in the presence of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA), N‐methyl‐d‐aspartate (NMDA) and γ‐aminobutyric acid [GABA(A)] receptor antagonists. In AHS tissue, barium caused a decrease in the baseline level of [K+]o. In contrast to non‐AHS slices, in AHS slices with intact synaptic transmission, barium had no effect on the stimulus‐induced rises of [K+]o, and the half time of recovery from the rise was less prolonged (by 57%). Under conditions of blocked synaptic transmission, barium augmented stimulus‐induced rises in [K+]o, but only by 40%. In both tissues, barium significantly reduced negative slow‐field potentials following repetitive stimulation but did not alter the mean population spike amplitude. The findings suggest a significant contribution of glial barium‐sensitive K+‐channels to K+‐buffering in non‐AHS tissue and an impairment of glial barium‐sensitive K+‐uptake in AHS tissue.