TRPV1 receptors augment basal synaptic transmission in CA1 and CA3 pyramidal neurons in epilepsy.

Temporal lobe epilepsy in human and animals is attributed to alterations in brain function especially hippocampus formation. Changes in synaptic activity might be causally related to the alterations during epileptogenesis. Transient receptor potential vanilloid 1 (TRPV1) as one of the non-selective ion channels has been shown to be involved in synaptic transmission. However, the potential role of TRPV1 receptors in synaptic function in the epileptic brain needs to be elucidated. In the present study, we used quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemistry to assess hippocampal TRPV1 mRNA expression, protein content, and distribution. Moreover, the effects of pharmacologic activation and inhibition of TRPV1 receptors on the slope of evoked field excitatory postsynaptic potentials (fEPSPs) were analyzed in CA1 and CA3 pyramidal neurons, after 3months of pilocarpine-induced status epilepticus (SE). SE induced an upregulation of TRPV1 mRNA and protein content in the whole hippocampal extract, as well as its distribution in both CA1 and CA3 regions. Activation and inhibition of TRPV1 receptors (via capsaicin 1µM and capsazepine 10µM, respectively) did not influence basal synaptic transmission in CA1 and CA3 regions of control slices, however, capsaicin increased and capsazepine decreased synaptic transmission in both regions in tissues from epileptic animals. Taken together, these findings suggest that a higher expression of TRPV1 in the epileptic condition is accompanied by alterations in basal synaptic transmission.

The Effect of Personality Traits of Managers/Supervisor on Job Satisfaction of Medical Sciences University Staffs.

BACKGROUND: Todays people are spending most of their time life in their workplace therefore investigation for job satisfaction related factors is necessities of researches. AIM: The purpose of this research was to analyze the effect of manager's personality traits on employee job satisfaction. SUBJECTS AND METHODS: The present study is a descriptive and causative-comparative one utilized on a statistical sample of 44 managers and 119 employees. It was examined and analyzed through descriptive and inferential statistics of Student's t-test (independent T), one-way ANOVA, and Kolmogorov-Smirnov test. RESULTS: Findings showed that the managers and supervisors with personality traits of extraversion, eagerness to new experiences, adaptability, and dutifulness had higher subordinate employee job satisfaction. However, in the neurotic trait, the result was different. CONCLUSION: The results showed that job satisfaction was low in the aspect of neurosis. Based on this, it is suggested that, before any selection in managerial and supervisory positions, candidates receive a personality test and in case an individual has a neurotic trait, appropriate interference takes place both in this group and the employees' one.

Altered inhibition in the hippocampal neural networks after spreading depression.

Prolonged neuronal depression after spreading depression (SD) is followed by a late cellular and synaptic hyperexcitability. Intra- and extracellular recordings of bioelectrical activities were performed in the rodent hippocampus to investigate the role of γ-aminobutyric acid (GABA)-mediated inhibition in the late hyperexcitable state of SD. The effect of KCl-induced negative DC potential shifts was investigated on extracellularly recorded paired-pulse depression (PPD) and bicuculline-induced afterdischarges as well as intracellularly recorded inhibitory post synaptic potentials (IPSPs) in the hippocampal CA1 area. The results revealed that SD decreased the degree of PPD, enhanced the number and duration of bicuculline-induced afterdischarges, and reduced the amplitude and duration of IPSPs. Application of low concentrations of bicuculline before the induction of SD enhanced the inhibitory effect of SD on IPSPs. Data indicate the contribution of GABA-mediated inhibition to SD-induced delayed hyperexcitability. Modulation of GABA function in the late hyperexcitability phase of SD may play a role in therapeutic management of SD-related neurological disorders.

Cognitive impairments and neuronal injury in different brain regions of a genetic rat model of absence epilepsy.

Growing numbers of evidence indicate that cognitive impairments are part of clinical profile of childhood absence epilepsy. Little is known on neuropathological changes accompanied by cognitive deficits in absence epilepsy. The aim of the present study was to investigate age-dependent neuropathological changes accompanied by learning and memory impairments in Wistar Albino Glaxo from Rijswijk (WAG/Rij) rat model of absence epilepsy. Experimental groups were divided into four groups of six rats of both WAG/Rij and Wistar strains with 2 and 6 months of age. The learning and memory performances were assessed using passive avoidance paradigm and neuropathological alterations were investigated by the evaluation of the number of dark neurons and apoptotic cells as well as the expression of caspase-3 in the neocortex, the hippocampus, and different regions of the thalamus. Results revealed a decline in learning and spatial memory of 6-month-old WAG/Rij rats compared to age-matched Wistar rats as well as 2-month-old WAG/Rij and Wistar rats. The mean number of dark neurons was significantly higher in the hippocampal CA1 and CA3 areas as well as in the laterodorsal, centromedial, and reticular thalamic nuclei and the somatosensory cortex of 6-month-old WAG/Rij rats. In addition, a higher number of apoptotic cells as well as a higher expression of caspase-3 was observed in the hippocampal CA1 and CA3 regions, the laterodorsal thalamic nucleus, and the somatosensory cortex of 6-month-old WAG/Rij rats compared to other animal groups. These results indicate significant enhancement of neuronal damage and cell death accompanied by memory deficits after seizure attacks in a rat model of absence epilepsy. Seizure-induced neuronal injury and death may underlie cognitive impairments in absence epilepsy.

The effect of new emergency program on patient length of stay in a teaching hospital emergency department of Tehran.

BACKGROUND AND AIM: Ideally, the period of patients admitting in the Emergency Department (ED) should not exceed 6 hours. Prolonged of the patients admitting time affects the ED overcrowding, quality of patient care and patient satisfaction. To evaluate the efficacy of new programs and suggest new strategies to reduce the overcrowding in a typical overcrowded ED of general teaching hospital in Tehran city. MATERIALS AND METHODS: In this descriptive case study, charts of patients held over 24 hours, in Imam Hossein Hospital affiliated to the Shaheed Beheshti Medical University, were reviewed from April 21(rd) on August 23(rd), 2008. RESULTS: Of 15,477 patients, 151 (1%) have been held in the ED over 24 hours. Reasons for this long-stay included:lack of available bed in Intensive Care Unit (ICU) (125 patients), lack of available bed in related wards (18 patients), poor final decision - making by physician (eight patient). CONCLUSION: Long-term stay of patients in ED of teaching hospital is a major problem. The most frequent cause is a limitation of inpatient beds. The long stay time had not been affected by paraclinic procedures, multispecialities involvement or the lack of obvious diagnosis. The following solution is proposed: (1) creation of a holding unit, (2) active inter-facility transfer and (3) governing admittance of patients who need ICU care to related wards.

Interstitial amino acid concentrations in rodent brain tissue during chemical ischemia.

The significance of electrophysiological phenomena is well validated in brain ischemia research. A close link with interstitial amino acid levels has not been proved convincingly but is generally assumed. This has given widespread rise to the clinical method of amino acid, especially glutamate, microdialysis. We combined microdialytic and electrophysiological techniques in an in vitro ischemia model to test for such a correlation. Rodent hippocampal brain slices were subjected to various patterns of ischemic simulation by depletion of glucose and oxygen and to K+ superfusion, which is often used as an alternative stressor. Our data do not strengthen the significance of clinically standardized glutamate measurements, insofar as ischemia-induced damage was demonstrated by electrophysiology and histology before being clearly mirrored by interstitial glutamate levels. Taurine would be a more promising candidate. K+ is not an adequate substitute for ischemic simulation, because biochemical and electrophysiological reactions of the tissue are clearly different. In vitro microdialysis during ischemic simulation is feasible and might provide a tool to inquire into glial functions during ischemic stress. It is probably not able to elucidate processes within the synaptic cleft.

Cortical spreading depression modulates the caudate nucleus activity.

Cortical spreading depression (CSD) plays an important role in migraine with aura. The caudate nucleus has crucial functional interactions with brain regions likely to be important in migraine. The aim of the present in vitro study was to investigate the effect of CSD on the neuronal activity of the caudate. Intracellular recording was performed in the head of the caudate nucleus alongside of extracellular recording in Wistar rat somatosensory cortex. CSD was induced by local KCl injection. Changes in the membrane potentials of the caudate neurons began 1.2±0.2min after CSD. The neurons of the caudate nucleus depolarized first gradually and slightly then it depolarized abruptly at nearly the same point of time of the recovery of the cortical DC potential. Action potentials (APs) reappeared after the cortical DC shift returned to the baseline. Forty-five minutes after CSD, the caudate neurons showed lower frequency of APs and larger amplitude of depolarization prior to APs. The firing pattern of the caudate neurons evoked by injection of intracellular current pulses changed from slow adapting to fast adapting after CSD. Reduced neuronal activity in the caudate after CSD may be assumed to contribute to pain as well as changes in cognition and behavior in patients with migraine.

Closed traumatic brain injury model in sheep mimicking high-velocity, closed head trauma in humans.

To date, there are only a few, non-evidence based, cerebroprotective therapeutic strategies for treatment and, accordingly, for prevention of secondary brain injuries following severe closed head trauma. In order to develop new therapy strategies, existing realistic animal models need to be advanced. The objective is to bridge standardized small animal models and actual patient medical care, since the results of experimental small animal studies often cannot be transferred to brain-injured humans. For improved standardization of high-velocity trauma, new trauma devices for initiating closed traumatic brain injury in sheep were developed. The following new devices were tested: 1. An anatomically shaped rubber bolt with an integrated oscillation absorber for prevention of skull fractures; 2. Stationary mounting of the bolt to guarantee stable experimental conditions; 3. Varying degrees of trauma severity, i. e., mild and severe closed traumatic brain injury, using different cartridges; and 4. Trauma analysis via high-speed video recording. Peritraumatic measurements of intracranial pressure, brain tissue pH, brain tissue oxygen, and carbon dioxide pressure, as well as neurotransmitter concentrations were performed. Cerebral injuries were documented with magnetic resonance imaging and compared to neuropathological results. Due to the new trauma devices, skull fractures were prevented. The high-speed video recording documented a realistic trauma mechanism for a car accident. Enhancement of extracellular glutamate, aspartate, and gamma amino butyric acid concentrations began 60 min after the trauma. Magnetic resonance imaging and neuropathological results showed characteristic injury patterns of mild, and severe, closed traumatic brain injury. The severe, closed traumatic brain injury group showed diffuse axonal injuries, traumatic subarachnoid hemorrhage, and hemorrhagic contusions with inconsistent distribution among the animals. The model presented here achieves a gain in standardization of severe, closed traumatic brain injury by increasing approximation to reality. The still existent heterogeneity of brain pathology mimics brain changes observed in patients after high-energy trauma. This model seems to close the gap between experimental small animal models and clinical studies. However, further investigations are needed to evaluate if this model can be used for testing new therapeutic strategies for these patients.

Remote switching of temperature, gaseous, and aqueous phase in a low-volume interface chamber for brain slices.

A new remote-controlled interface-type chamber was designed in order to conduct experiments in brain slices involving gas, fluid, and temperature changes with as little tissue manipulation as possible. The chamber allows for extremely quick changes between different fluid and/or gaseous phases and for active cooling as well as heating by using a set of electromechanical valves and Peltier elements. The design drawings are complemented by exemplary tests of temperature and gas changes, and electrophysiological recordings of slices manipulated with gas and fluid alterations were used to test the efficacy and accuracy of the design. Changing between normoxia and anoxia needs less than 30 s, while the readjustment of the chamber to a new, preset temperature is accomplished in about 1 min. Supplementary data provide a proposal for the electronic circuit diagram. This chamber design should simplify data acquisition in interface environments.

The effect of repetitive spreading depression on neuronal damage in juvenile rat brain.

Spreading depression (SD) is pronounced depolarization of neurons and glia that travels slowly across brain tissue followed by massive redistribution of ions between intra- and extracellular compartments. There is a relationship between SD and some neurological disorders. In the present study the effects of repetitive SD on neuronal damage in cortical and subcortical regions of juvenile rat brain were investigated. The animals were anesthetized and the electrodes as well as cannula were implanted over the brain. SD-like event was induced by KCl injection. The brains were removed after 2 or 4 weeks after induction of 2 or 4 SD-like waves (with interval of 1 week), respectively. Normal saline was injected instead of KCl in sham group. For stereological study, paraffin-embedded brains were cut in 5 microm sections. The sections were stained with Toluidine Blue to measure the volume-weighted mean volume of normal neurons and the numerical density of dark neurons. The volume-weighted mean volume of normal neurons in the granular layer of the dentate gyrus and layer V of the temporal cortex in SD group were significantly decreased after four repetitive SD. Furthermore, densities of dark neurons in the granular layer of the dentate gyrus (after 2 weeks), the caudate-putamen, and layer V of the temporal cortex (after 4 weeks) were significantly increased in SD group. Repetitive cortical SD in juvenile rats may cause neuronal damage in cortical and subcortical areas of the brain. This may important in pathophysiology of SD-related neurological disorders.

Thalamic afferent activation of supragranular layers in auditory cortex in vitro: a voltage sensitive dye study.

We studied auditory thalamocortical interactions in vitro, using an auditory thalamocortical brain slice preparation. Cortical activity evoked by electrical stimulation of the medial geniculate nucleus (MGN) was investigated through field potential recordings and voltage sensitive dyes. Experiments were performed in slices obtained from adult mice (9-14 weeks). Stimulus evoked activity was detected in the granular and supragranular layers after a short latency (5-6 ms). In 9-14 weeks old mice infragranular activity was detected in 10 of 24 preparations and was found to be increased in younger mice (p 31-64). In 14 of 24 slices a prominent horizontal spread was observed, which extended into cortical areas lateral to A1. In these experiments, the shortest onset latencies and largest signal amplitudes were located in the supragranular layers of A1. In areas lateral to A1, shortest onset latencies were located in the granular layer, while largest signal amplitudes were found in the supragranular layers. Evoked cortical activity was sensitive to removal of extracellular Ca(2+) or application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM). Short repetitive stimulation, resembling thalamic burst activity (three pulses at 100 Hz), resulted in an increase of signal amplitude and excited area by approximately 25%, without changing the overall spatiotemporal activity profile. Blockade of N-methyl-D-aspartate receptors by 2-amino-5-phosphonopentanoate (AP5, 50 microM) reduced amplitudes and excited area by approximately 15-30%, irrespective of stimulation frequency. Application of bicuculline (10 microM) greatly increased cortical responses to thalamic stimulation. Under these conditions, evoked activity displayed a pronounced horizontal spread in combination with a 2-3-fold increase in amplitude. In conclusion, afferent thalamic inputs primarily activate supragranular and granular layers in the auditory cortex of adult mice. This activation is predominantly mediated by non-NMDA receptors, while GABA(A) receptor-mediated inhibition limits the horizontal and vertical spread of activity.

Patterns of neurotransmitter receptor distributions following cortical spreading depression.

Spreading depression (SD), a self-propagating depolarization of neurons and glia, is believed to play a role in different neurological disorders including migraine aura and acute brain ischaemia. Initiation and propagation of SD modulate excitability of neuronal network. A brief period of excitation heralds SD which is immediately followed first by prolonged nerve cell depression and later by an excitatory phase. The aim of the present study was to characterize local and remote transmitter receptor changes after propagation of cortical SD. Quantitative receptor autoradiography was used to asses 16 transmitter receptor types in combined striatum-hippocampus-cortex slices of the rat 1 h after induction of cortical SD. In neocortical tissues, local increases of glutamate NMDA, AMPA, and kainate receptor binding sites were observed. In addition to up-regulation of ionotropic glutamate receptors, receptor binding sites of GABA(A), muscarinic M1 and M2, adrenergic alpha(1) and alpha(2), and serotonergic 5-HT(2) receptors were increased in the hippocampus. Cortical SD also upregulated NMDA, AMPA, kainate, GABA(A), serotonergic 5-HT(2), adrenergic alpha(2) and dopaminergic D1 receptor binding sites in the striatum. These findings indicate selective changes in several receptors binding sites both in cortical and subcortical regions by SD which may explain delayed excitatory phase after SD. Mapping of receptor changes by cortical SD increases our understanding of the mechanism of SD action in associated neurological disorders.

Hyperbaric oxygen in neurosurgery.

BACKGROUND: The therapeutic use of pure oxygen, even under hyperbaric conditions, has been well established for about 50 years, whereas the discovery of oxygen occurred 250 years earlier. Many neurosurgical patients suffer from brain tissue damage, due to reduced blood flow, obstructive vessel disease, or as a result of traumatic brain injury. METHODS AND RESULTS: The application of pure oxygen in these patients is the only method of increasing the O(2) concentration in tissue with impaired blood supply and can minimize secondary impairment of brain tissue. DISCUSSION: In this brief historical overview we focus on the development and evidence of hyperbaric oxygenation in this specific field of insufficient oxygen supply to the central neural tissue. CONCLUSION: With the use of modern biological methods and new study designs, HBO has a place in evidence-based treatment of patients with neural tissue damage.

Influences of pCO2 and bicarbonate concentration on bioelectric phenomena in ischemic hippocampal ex vivo tissue.

While the vasomotor effects of pCO(2) modulation are well documented, the influence of the carbon dioxide-bicarbonate system on the ischemia tolerance of brain tissue itself is controversial. Guinea-pig hippocampal tissue was subjected to ischemia simulation in an interface environment and examined electrophysiologically. Characteristics of anoxic depolarization as well as the postischemic recovery of evoked potentials were registered. During ischemia simulation, pH was changed and afterwards restored to 7.4. pH of 7.6 (n=6), and 7.8 (n=6) were adjusted by increasing bicarbonate concentration without changing pCO(2), while pH 8.2 was reached either with normal pCO(2) (n=8) or with zero CO(2) (n=9). pH 7.1 was created by doubling pCO(2) (n=22) or reducing bicarbonate (n=21), while acid pH of 6.9 (high pCO(2) and low bicarbonate) led to erratic measurements in the interface setup. Alkalotic conditions did not improve electrophysiological stability of the tissue, and pH 8.2 impeded the recovery of evoked potentials. Hypercarbic pH 7.1 led to significantly longer latency of depolarization while the same pH with lowered bicarbonate did not. Evoked potentials, however, recovered only partially after ischemia at hypercarbic pH 7.1. Once the tissue had recovered from anoxic depolarization at control pH, hypercarbic acidosis did not have any further protective effect when ischemia simulation was repeated (n=12). These results do not strengthen the concept of hyperventilation in intensive care, while they suggest a potential of hypercarbia within broader strategies delaying the onset of secondary brain damage.

Spreading depression enhances human neocortical excitability in vitro.

Cortical spreading depression (CSD) plays a role in migraine with aura. However, studies of the neuronal effects of CSD in human cortex are scarce. Therefore, in the present study, the effects of CSD on the field excitatory postsynaptic potentials (fEPSP) and the induction of long-term potentiation (LTP) were investigated in human neocortical slices obtained during epilepsy surgery. CSD significantly enhanced the amplitude of fEPSP following a transient suppressive period and increased the induction of LTP in the third layer of neocortical tissues. These results indicate that CSD facilitates synaptic excitability and efficacy in human neocortical tissues, which can be assumed to contribute to hyperexcitability of neocortical tissues in patients suffering from migraine.

Different regional neuroinhibitory effects of adenosine on stimulus-induced patterns of bioelectric activity of rat hippocampal and neocortical tissues.

Adenosine is an inhibitory modulator of brain activity with neuroprotective and anticonvulsant properties. To investigate the distribution of bioelectric activities under application of adenosine, rat hippocampal and neocortical slices were incubated with the voltage-sensitive dye RH795 and neuronal activity was monitored using a fast-imaging photodiode array combined with standard field potential recordings. The effects of adenosine (1-50 micromol/l) on the spatial distribution of stimulus-induced activities were studied in non-epileptiform as well as epileptiform conditions. Epileptiform activity was induced by omission of Mg(2+) from the bath medium. The adenosine's inhibitory effects on the amplitude and spatial extent of stimulus-induced bioelectric activity in the hippocampus were most prominent in strata radiatum and pyramidale in both control and epileptic mediums. Adenosine's inhibitory actions were different on various layers of neocortical tissues in non-epileptiform and epileptiform conditions. Layers II and III showed the most inhibition by application of adenosine in control slices. In epileptiform medium, however, adenosine exerts significant suppressive effects only in layer I of neocortical slices. The data demonstrate a region-specific modulatory potential of adenosine on neuronal network excitability in the hippocampus and neocortex. This may be important in local adenosine therapy in epilepsy.

Effect of eugenol on spreading depression and epileptiform discharges in rat neocortical and hippocampal tissues.

Eugenol, an aromatic molecule derived from several plants, has been receiving examination for clinical relevance in epilepsy and headache. To investigate the neurophysiologic properties of the action of eugenol, its effects on epileptiform field potentials elicited by omission of extracellular Mg2+, spreading depression induced by KCl microinjection, electrically evoked field potentials, and long-term potentiation were tested in rat neocortical and hippocampal tissues. Eugenol (10-100 micromol/l) dose-dependently and reversibly suppressed both epileptiform field potentials and spreading depression Eugenol also reversibly decreased the amplitude of the field postsynaptic potentials evoked in CA1 area of hippocampus and the third layer of neocortex. Eugenol significantly reduced the long-term potentiation by approximately 30% compared with controls. Thus, eugenol can suppress epileptiform field potentials and spreading depression, likely via inhibition of synaptic plasticity. The results indicate the potential for eugenol to use in the treatment of epilepsy and cephalic pain.

Epilepsy surgery: perioperative investigations of intractable epilepsy.

Recent advances in our understanding of the basic mechanisms of epilepsy have derived, to a large extent, from increasing ability to carry out detailed studies on patients surgically treated for intractable epilepsy. Clinical and experimental perioperative studies divide into three different phases: before the surgical intervention (preoperative studies), on the intervention itself (intraoperative studies), and on the period when the part of the brain that has to be removed is available for further investigations (postoperative studies). Before surgery, both structural and functional neuroimaging techniques, in addition to their diagnostic roles, could be used to investigate the pathophysiological mechanisms of seizure attacks in epileptic patients. During epilepsy surgery, it is possible to insert microdialysis catheters and electroencephalogram electrodes into the brain tissues in order to measure constituents of extracellular fluid and record the bioelectrical activity. Subsequent surgical resection provides tissue that can be used for electrophysiological, morphological, and molecular biological investigations. To take full advantage of these opportunities, carefully designed experimental protocols are necessary to compare the data from different phases and characterize abnormalities in the human epileptic brain.

Characterization of a fast transient outward current in neocortical neurons from epilepsy patients.

A-type currents powerfully modulate discharge behavior and have been described in a large number of different species and cell types. However, data on A-type currents in human brain tissue are scarce. Here we have examined the properties of a fast transient outward current in acutely dissociated human neocortical neurons from the temporal lobe of epilepsy patients by using the whole-cell voltage-clamp technique. The A-type current was isolated with a subtraction protocol. In addition, delayed potassium currents were reduced pharmacologically with 10 mM tetraethylammonium chloride. The current displayed an activation threshold of about -70 mV. The voltage-dependent activation was fitted with a Boltzmann function, with a half-maximal conductance at -14.8 +/- 1.8 mV (n = 5) and a slope factor of 17.0 +/- 0.5 mV (n = 5). The voltage of half-maximal steady-state inactivation was -98.9 +/- 8.3 mV (n = 5), with a slope factor of -6.6 +/- 1.9 mV (n = 5). Recovery from inactivation could be fitted monoexponentially with a time constant of 18.2 +/- 7.5 msec (n = 5). At a command potential of +30 mV, application of 5 mM 4-aminopyridine or 100 microM flecainide resulted in a reduction of A-type current amplitude by 35% or 22%, respectively. In addition, flecainide markedly accelerated inactivation. Current amplitude was reduced by 31% with application of 500 microM cadmium. All drug effects were reversible. In conclusion, neocortical neurons from epilepsy patients express an A-type current with properties similar to those described for animal tissues.

Natural remedies for impotence in medieval Persia.

Man's preoccupation with potency, or the lack thereof, has been present through the ages. Several documents still exist from which the clinical approaches of erectile dysfunction (ED) in medieval Persia can be ascertained. The medieval physicians described definitions and apparent causes of ED. They also noted hygienic and dietary rules as well as long lists of natural substances used in the treatment of ED. Many of the approaches of practitioners in medieval Persia are accurate and accepted even today; however, still more of them could be of use to modern medicine. The present review provides an overview of the knowledge of ED at the time.