Microglia Drive Pockets of Neuroinflammation in Middle Age.

During aging, microglia produce inflammatory factors, show reduced tissue surveillance, altered interactions with synapses, and prolonged responses to CNS insults, positioning these cells to have profound impact on the function of nearby neurons. We and others recently showed that microglial attributes differ significantly across brain regions in young adult mice. However, the degree to which microglial properties vary during aging is largely unexplored.

Association between preoperative peripheral blood mononuclear cell gene expression profiles, early postoperative organ function recovery potential and long-term survival in advanced heart failure patients undergoing mechanical circulatory support.

Background: Multiorgan dysfunction syndrome contributes to adverse outcomes in advanced heart failure (AdHF) patients after mechanical circulatory support (MCS) implantation and is associated with aberrant leukocyte activity. We tested the hypothesis that preoperative peripheral blood mononuclear cell (PBMC) gene expression profiles (GEP) can predict early postoperative improvement or non-improvement in patients undergoing MCS implantation. We believe this information may be useful in developing prognostic biomarkers.

Physiological and anatomical correlates of the human dentate gyrus: consequences or causes of epilepsy.

The presence of paroxysmal discharges in the epileptic human dentate gyrus provides a physiologic basis for hyperexcitability that may initiate seizure discharges during the development of epilepsy. Although these responses can occur with single orthodromic stimulation, data obtained under conditions that weaken synaptic inhibition (e.g.

Paroxysmal discharges in the EL mouse, a genetic model of epilepsy.

The EL/Suz (EL) mouse is a strain that is highly susceptible to convulsive seizures after repeated sensory stimulation. Its control strain, DDY/Jc1 (DDY), is less susceptible under similar conditions. The seizure prone phenotype is the result of differences at several genetic loci.

Mossy fiber reorganization and its possible physiological consequences in the dentate gyrus of epileptic humans.

It is unlikely that MF reorganization is the cause of epilepsy, but it may affect the progression of the disease, i.e., the frequency or severity of seizures.

Changes in dentate granule cell field potentials during afterdischarge initiation triggered by 5 Hz perforant path stimulation.

A failure of early paired pulse depression often precedes the onset of intermittent spontaneous seizures in animal models of status epilepticus. In the present study, changes in the strength of early and late paired pulse depression of dentate granule cell field potentials were compared in the unanesthetized rat during the initiation of a single afterdischarge (AD) evoked by perforant path stimulation (0.1 ms pulse duration, 5 Hz, 12-18 s duration, 50-1000 microA).

Prolonged field potentials evoked by 1 Hz stimulation in the dentate gyrus of temporal lobe epileptic human brain slices.

An abnormal electrophysiological response in brain slices of the dentate gyrus from biopsy material from patients surgically treated for intractable epilepsy (46/57), exhibited characteristics similar to the physiological hallmark of epilepsy, the paroxysmal discharge, a prolonged (30-600 ms) and often large amplitude field potential. The most striking feature of the prolonged response to a single perforant path stimulus was a predominantly biphasic field potential (23/46 cases). The biphasic response was characterized by a negative field potential of substantial duration exceeding 180 ms which followed an initial shorter duration positive field potential.

Hippocampal cell distributions in temporal lobe epilepsy: a comparison between patients with and without an early risk factor.

Neuronal cell distributions were measured for anterior and posterior locations in the hippocampi of epilepsy patients who were seizure-free after temporal lobectomy. Patients were divided into two groups, those with an early risk factor, defined as a neurologic insult occurring in the first 4 years of life, and those with no early risk factor. Early-risk patients had lower hilar cell densities, lower granule cell densities, and fewer granule cells per millimeter, a measured related to total granule cell number, than to early risk patients.

Effects of bicuculline and baclofen on paired-pulse depression in the dentate gyrus of epileptic patients.

Paired-pulse field responses were recorded from the granule cell layer of the dentate gyrus in brain slices from temporal lobe epileptic patients. Paired-pulse depression (PPD) was examined using perforant path stimulation of low to moderate intensity at an inter-stimulus interval (ISI) of 20 ms. The paired-pulse ratio (PS2/PS1) was expressed as the population spike amplitude of the second response (PS2) relative to that of the first response (PS1).

Stimulus parameters affecting paired-pulse depression of dentate granule cell field potentials. II. Low-frequency stimulation.

Low frequency (1 Hz) stimulation of the perforant path produces a depression in the population spike (PS) of dentate granule cell field potentials and also may affect the strength of paired pulse depression. The effects of 1 Hz stimulation (30 s train) on paired pulse depression (20 and 200 ms interpulse intervals, IPI) were evaluated in the unanesthetized rat under two conditions: (i) when the stimulus intensity of both pulses was increased simultaneously (5-100%); and (ii) when the stimulus intensity of the first (conditioning) pulse was increased (5-100%), while the stimulus intensity of the second (test) pulse was held constant (50%). The test PS amplitude was predicted based upon either the conditioning PS amplitude at the end of the 1 Hz train or upon the additive effects of paired pulse depression and 1 Hz stimulation.

Longitudinal variation in cell density and mossy fiber reorganization in the dentate gyrus from temporal lobe epileptic patients.

Variation in cell loss and mossy fiber reorganization was examined along the longitudinal axis of the dentate gyrus from temporal lobe epileptic (TLE) patients. Previous evidence has indicated that the anterior hippocampus is prone to seizure activity. We compared granule and hilar cell number in addition to Timm stain density of the molecular layer and hilus in more anterior and more posterior specimens of hippocampus obtained from patients surgically treated for intractable epilepsy by the removal of the anterior half of the hippocampus.

Polyamine effects on the NMDA receptor in human brain.

Polyamines are thought to modulate the activation of NMDA receptors through a unique allosteric regulatory site. The effects of polyamines on the binding of [3H]MK-801 were measured in cortical and hippocampal tissue surgically removed from patients with temporal lobe epilepsy (TLE). The polyamine agonist spermidine increased the binding of [3H]MK-801 in the cortex in a dose-dependent manner and this effect could be blocked by the weak partial agonist diethylenetriamine (DET).

Alterations of inhibitory synaptic responses in the dentate gyrus of temporal lobe epileptic patients.

The number of orthodromically evoked population spikes was used to classify brain slice tissue from the dentate gyrus of temporal lobe epileptic patients as "more excitable" (multiple population spikes) or "less excitable" (a single population spike). During orthodromic stimulation, "more excitable" tissue exhibited less paired-pulse depression in comparison to "less excitable" tissue. During antidromic stimulation, both multiple population spikes and paired-pulse depression were observed in "more excitable" tissue.

Hyperexcitability associated with localizable lesions in epileptic patients.

Intracellular recordings from neurons were carried out in cortical slices obtained from tissue removed from patients suffering from intractable seizures. The patients were divided into two groups based on the presence or absence of an anatomical abnormality that could be imaged preoperatively. The lesion or its surround was the presumptive epileptogenic area.

The functional relationship between antidromically evoked field responses of the dentate gyrus and mossy fiber reorganization in temporal lobe epileptic patients.

Field recordings from the dentate granule cell layer of in vitro brain slices of temporal lobe epileptic patients were evoked by antidromic stimulation. Tissue from the same specimen was stained by the Timm-sulfide method to assess the pattern and degree of mossy fiber reorganization into the supragranular layer. A wide range of physiological responses and Timm staining patterns was present across patients.

NMDA receptor activation during epileptiform responses in the dentate gyrus of epileptic patients.

We previously showed that a low frequency (1 Hz) train of perforant path stimulation evokes burst discharges in the dentate gyrus of hippocampal slices obtained from patients surgically treated for intractable temporal lobe epilepsy. We report here that multiple population spikes that characterize the burst discharge are blocked reversibly by the specific NMDA receptor antagonist, D-(-)-2-amino-5-phosphonovaleric acid (D-APV). The epileptiform discharge evoked in human dentate gyrus by stimulation trains of 1 Hz could be reproduced in the rat dentate gyrus in vitro by the same stimulation protocol but required the presence of low concentrations (0.

Distribution of single-channel conductances in cultured rat hippocampal neurons.

1. The nonhomogeneous spatial distribution of ionic channels in neurons has been implied from intracellular recordings at somatic and dendritic locations. These reports indicate that Na- and Ca-dependent regenerative currents are distributed differently throughout the neuron.

Hippocampal neuronal density in temporal lobe epilepsy with and without gliomas.

The majority of patients with temporal lobe epilepsy show hippocampal sclerosis, which pathologically represents neuronal loss and gliosis. We studied volumetric neuronal density on a representative mid to mid-posterior level slice of hippocampi surgically removed from intractable temporal lobe epilepsy cases, and compared the results between 25 non-tumor epilepsy (NTE) cases and 5 tumor-associated epilepsy (TAE) cases. Eleven age-matched non-epileptic autopsy cases were studied as controls.

Epileptiform discharges evoked in hippocampal brain slices from epileptic patients.

We have recorded from diseased hippocampal tissue which was surgically removed from epileptic patients for therapeutic purposes. When the perforant path was stimulated at a low frequency (1 Hz), the number of population spikes evoked in the dentate gyrus increased by a factor of as great as 8 during a 15 s train. This effect was transient.

Excitable properties of olfactory receptor neurons.

Action potential-generating properties of olfactory receptor neurons in the olfactory epithelium of the salamander, Ambystoma tigrinum, were studied in control animals, and 2 and 4 weeks after olfactory nerve transection. The threshold for impulse generation in response to injected current was extremely low (74 +/- 46 pA). In addition, the discharge frequencies of the receptor neurons were exquisitely sensitive to small increments of injected current.

Temperature dependence of intrinsic membrane properties and synaptic potentials in hippocampal CA1 neurons in vitro.

The temperature dependence of intrinsic membrane conductances and synaptic potentials in guinea pig hippocampal CA1 pyramidal neurons were examined in vitro as they were cooled from 37 degrees C to between 33 and 27 degrees C. Cooling reversibly increased resting input resistance in a voltage-independent manner (Q10 = 0.58 to 0.

Changes in the electrical properties of olfactory epithelial cells in the tiger salamander after olfactory nerve transection.

Transection of olfactory nerves causes degeneration of receptor neurons in the olfactory epithelium, followed by generation of new receptor neurons. We have carried out intracellular recordings to document changes in epithelial cell populations during receptor neuron degeneration and regrowth at 1, 2, and 4 weeks following olfactory nerve transection in the salamander. Receptor neurons were greatly reduced in numbers at 1 week, and gradually returned to the normal percentage of intracellular penetrations by 4 weeks.

Electrophysiological properties of identified cells in the in vitro olfactory epithelium of the tiger salamander.

An in vitro preparation of the salamander olfactory epithelium has been developed for electrophysiological analysis. Intracellular measurements of membrane properties of the main epithelial cell types have been carried out, combined with Lucifer Yellow injections. The most prevalent type of cell had a high resting membrane potential and relatively low input resistance.

Synaptic control of excitability in isolated dendrites of hippocampal neurons.

The apical dendrites of CA1 pyramidal cells were isolated from their cell bodies by making cuts through proximal stratum radiatum of transverse hippocampal slices from the guinea pig. This lesion separated the distal apical dendritic elements from the somata, basal dendrites, and 50 to 100 microns of the proximal apical dendritic tree. Orthodromic stimuli in stratum radiatum evoked excitatory synaptic responses in isolated dendrites, but no phasic inhibitory components could be detected.

A comparison of nerve transection and chronic application of beta-bungarotoxin on acetylcholine receptor distribution and other nerve-muscle properties.

beta-Bungarotoxin (beta-BuTX), a snake venom neurotoxin which acts presynaptically to inhibit acetylcholine (ACh) release at the neuromuscular junction, was applied to the rat phrenic nerve-diaphragm muscle preparation to determine its effectiveness to mimic denervation. The distribution of junctional and extrajunctional ACh receptors on the muscle were assayed biochemically by [125I]alpha-bungarotoxin ( [125I]alpha-BuTX) binding and electrophysiologically by iontophoretic application of ACh. Spontaneous transmitter release and muscle membrane potential were measured under conditions of denervation, beta-BuTX treatment, and bee venom phospholipase A2 exposure.