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.

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.

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.

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.

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.

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.

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.

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.

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.

History of epilepsy in Medieval Iranian medicine.

The history of epilepsy in Medieval Persian medicine is not well-known in the Western world. This article presents the clinical approaches according to which Medieval Iranian practitioners viewed epilepsy and dealt with its problems. The clinical viewpoints of epilepsy are collected from Medieval Persian scientific references. These describe clinical manifestations, basic mechanisms, etiologies, treatment and prognosis. Medieval Iranian practitioners provide detailed clinical information on epilepsy. They mention various forms and symptoms of epilepsy and its apparent causes and offer dietary and hygienic rules, as well as a long list of pharmacologic compounds for treating it. Their findings about epilepsy are very accurate and vivid and many of them are accepted even today.

Epileptogenic effect of cyclosporine in guinea-pig hippocampal slices.

Cyclosporine A (CsA) neurotoxicity is a common cause of seizures in transplant patients and others receiving immunosuppressive therapy. CsA at concentrations higher than the levels estimated for cerebrospinal fluid of the patients suffering from seizure attacks was ineffective to induce epileptiform field potentials (EFP) in in vitro brain-slice preparation. The aim of this study was to test the effect of CsA at lower concentrations on neuronal activity. Guinea-pig hippocampal slices were exposed to artificial cerebrospinal fluid containing CsA (0.1-2 microM). Furthermore, the effects of CsA (0.25-10 microM) were tested on EFP elicited by omission of Mg2+ from superfusate. Low concentrations of CsA (0.1-0.25 microM) induced EFP while higher doses (0.5-2 microM) failed to decrease the seizure threshold. CsA at concentrations of 0.25 and 1 microM had no significant effect on the low Mg2+-induced EFP. Higher CsA concentration (10 microM) strongly suppressed EFP. The results indicate that CsA at doses that are probably clinically relevant increases the neuronal excitability.

Stimulus-induced patterns of bioelectric activity in human neocortical tissue recorded by a voltage sensitive dye.

Stimulus-induced pattern of bioelectric activity in human neocortical tissue was investigated by use of the voltage sensitive dye RH795 and a fast optical recording system. During control conditions stimulation of layer I evoked activity predominantly in supragranular layers showing a spatial extent of up to 3000 microm along layer III. Stimulation in white matter evoked distinct activity in infragranular layers with a spatial extent of up to 3000 microm measured along layer V. The mean amplitude of optical signals close to the stimulated sites in layer I and white matter determined 25 ms following the stimulus, decreased by 50% at a lateral distance of approximately 900 microm and 1200 microm, respectively. Velocity of spread along the vertical stimulation axis reached 0.24 m/s in the supragranular layers (layers I to III) and then decreased to 0.09 m/s following layer I activation; stimulation of white matter induced a velocity of spread in layer V of 0.38 m/s, which slowed down to 0.12 m/s when passing the lower border of lamina IV. The horizontal velocities of spread determined from the stimulation site to a lateral distance of 500 microm reached 0.26-0.28 m/s and 0.28-0.35 m/s for layer I and white matter stimulation, respectively. At larger distances velocity of spread decreased. Increased excitability (Mg(2+)-free solution) had no significant effect on the spatio-temporal distribution of evoked activity as compared with control conditions. There were also no obvious differences between the results obtained in slices, which generated spontaneously sharp waves and those which were not spontaneously active. About 30% of the slices (n=7) displayed a greatly different response pattern, which seemed not to be related in a simple way to the stimulation as was the case in the majority of the investigated slices. The activity pattern of those slices appeared atypical in regard to their deviations of the vertical and horizontal extent of activity, to their reduced spatial extent of activity during increased excitability, to their layer-related distribution of activity, and to the appearance of afterdischarges.Concluding, in 30% of the human temporal lobe slices atypical activity pattern occurred which obviously reflect intrinsic epileptiform properties of the resected tissue. The majority of slices showed stereotyped activity pattern without evidence for increased excitability.

Background potassium concentrations and epileptiform discharges. I. Electrophysiological characteristics of neuronal activity.

Intra- and extracellular recording techniques were used to study the epileptiform activity generated by guinea pig hippocampal slices perfused with free-magnesium artificial cerebrospinal fluid in the presence of physiologic (4 mM), reduced (2 mM) or elevated (8 mM) extracellular potassium concentrations ([K(+)](o)). Extracellular field potentials along with intracellular recordings were recorded in CA1 or CA3 region. Reduction of [K(+)](o) significantly increased the latency of epileptiform field potential (EFP) appearance as well as burst discharge duration and decreased EFP repetition rate. Depending on different background [K(+)](o), epileptiform burst discharges appeared in different patterns including varied types of paroxysmal depolarisation shifts and burst activity in CA1 and CA3 subfields. Comparison with physiological and increased [K(+)](o,) reduction of [K(+)](o) significantly increased the mean duration of bursts, mean amplitude of depolarisation, mean after-hyperpolarisation duration, and inter-spike intervals in both CA1 and CA3 areas. Three distinct patterns were distinguished on the basis of their evoked firing pattern in response to application of depolarising current pulses in the interval of epileptiform burst discharges. Neurons superfused with 2 mM [K(+)](o) presented fast adapting pattern while cells washed with 4 or 8 mM [K(+)](o) exhibited intrinsically bursting or slow adapting patterns. Comparing the groups with different background [K(+)](o), there is a more severe form of discharges in low K(+) and a subtle difference between 4 and 8 mM K(+). The data indicate the importance of background [K(+)](o) on epileptiform burst discharge pattern and characteristics.

Background potassium concentrations and epileptiform discharges. II. Involvement of calcium channels.

Potassium- and calcium conductances regulate neuronal excitability and epileptiform activity. In this study, the effects of different extracellular potassium concentrations ([K(+)](o)) were investigated on the modulatory effect of the L-type transmembranous calcium currents on epileptiform discharges. The in vitro brain slice technique was used to examine the effects of calcium channel blockers, verapamil and nifedipine, on the repetition rate, amplitude, and duration of epileptiform field potentials (EFP) in the presence of low, physiological, and high background [K(+)](o) in guinea pig hippocampal slices. Epileptiform activity was induced by omission of Mg(2+) from artificial cerebrospinal fluid contained 2, 4, and 8 mM [K(+)](o). Both verapamil and nifedipine suppressed EFP after a transient increase in repetition rate. The extent of EFP frequency rate acceleration significantly increased with reduction of [K(+)](o). The increase in EFP frequency rate induced by application of verapamil and nifedipine was accompanied by a reduction in the EFP amplitude and a reversible increase in the burst discharge duration. The extent of burst discharge prolongation was also significantly higher with decreasing [K(+)](o). Further application of verapamil and nifedipine suppressed the epileptiform burst activity in the presence of different [K(+)](o). The latency of EFP depression was significantly diminished both with increased and decreased background potassium concentrations. The data indicate the importance of the effect of the L-type transmembranous calcium currents on the regulatory effect of background [K(+)](o) on epileptiform burst discharge frequency and duration.

Lowering of the potassium concentration induces epileptiform activity in guinea-pig hippocampal slices.

Extra- and intracellular recording techniques were used to study the epileptiform activity generated by guinea-pig hippocampal slices perfused with low potassium containing artificial cerebrospinal fluid. Extracellular field potentials were recorded in CA1 and CA3 regions along with intracellular recordings in CA3 subfield. Reduction of the extracellular potassium concentration [K(+)](o) from 4 to 2 mM caused a transient neuronal hyperpolarisation which was followed by a repolarisation and subsequent depolarisation period. Paroxysmal depolarisation shifts occurred during the transient hyperpolarisation period while epileptic field potentials (EFP) appeared in the late repolarisation or early depolarisation phase. EFP elicited by reduction of [K(+)](o) were neither affected by blockade of N-methyl-D-aspartate (NMDA) glutamate-subreceptor or gamma aminobutyric acid receptor, nor by application of the organic calcium channel blocker nifedipine or the anticonvulsant drugs carbamazepine and valproic acid. Upon application of non-NMDA glutamate-subreceptor blocker the EFP were abolished in all trials, while application of the organic calcium channel blocker verapamil only suppressed the EFP in some cases. The results point to a novel mechanism of epileptogenesis and may provide an in vitro model for the development of new drugs against difficult-to-treat epilepsy.

Spreading depression in human neocortical slices.

Cortical spreading depression (CSD) occurrence has been suggested to be associated with seizures, migraine aura, head injury and brain ischemia-infarction. Only few studies identified CSD in human neocortical slices and no comprehensive study so far evaluated this phenomenon in human. Using the neocortical tissue excised for treatment of intractable epilepsy, we aimed to investigate CSD in human. CSD was induced by KCl injection and by modulating T-type Ca(2+) currents in incubated human neocortical tissues in an interphase mode. The DC-fluctuations were recorded by inserting microelectrodes into different cortical layers. Local injection of KCl triggered single CSD that propagated at 3.1+/-0.1 mm/min. Repetitive CSD also occurred spontaneously during long lasting application (5 h) of the T-type Ca(2+) channel blockers amiloride (50 microM) or NiCl(2) (10 microM) which was concomitant with a reversible extracellular potassium increase up to 50 mM. CSD could be blocked by the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovaleric acid in all cases. The results demonstrate that modulation of the Ca(2+) dynamics conditioned human neocortical slices and increased their susceptibility to generate CSD. Furthermore, these data indicate that glutamatergic pathway plays a role in CSD phenomenon in human.

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.

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.