bluuebunny/crossref_metadata_2025_split huggingface dataset:
The transient depression of hippocampal CA1 LTP induced by chronic intermittent ethanol exposure is associated with an inhibition of the MAP kinase pathway
Authors: Roberto M. , Nelson T. E. , Ur C. L. , Brunelli M. , Sanna P. P. , Gruol D. L. 
Published: December 2004

AbstractUsing electrophysiological and biochemical approaches, we investigated the effects of chronic, intermittent ethanol (CIE) treatment on activation of the mitogen activated protein kinase (MAPK), also known as extracellular signal regulated protein kinase 1 and 2. In hippocampal slices taken from control rats, brief high‐frequency stimulation to Schaffer collateral fibers induced a large post‐tetanic potentiation (PTP) in the CA1 region that decayed to stable long‐term potentiation (LTP) of field extracellular postsynaptic potentials. Western blot analyses showed that phosphorylation of MAPK was increased during PTP and returned to baseline levels during LTP. In slices from the rats removed immediately from CIE treatment, PTP and MAPK activation during the PTP was significantly less than that observed in control slices and LTP was absent. In slices from rats subjected to 1 day withdrawal from CIE treatment, both the reduction in MAPK phosphorylation during PTP and the impairment of PTP and LTP were still evident. Recovery of PTP and partial recovery of LTP was observed in slices obtained from 5‐day withdrawn rats. However, MAPK activation during PTP was still attenuated significantly. Interestingly, MAPK activation was enhanced significantly during LTP in 5‐day withdrawn rats as well as the sensitivity to MAPK inhibitor PD 098059. In addition to these changes in HFS‐induced MAPK activation, we also observed a significant reduction in the basal phosphorylation of MAPK in slices removed from rats immediately after CIE treatment. These results implicate the MAPK signal transduction pathway as a potential cellular target of ethanol. Alterations in MAPKs could play an important role in the alcohol‐induced changes in synaptic plasticity associated with the effects of alcohol abuse on learning and memory processes.
Influence of auditory deprivation upon the tonopic organization in the inferior colliculus: a Fos immunocytochemical study in the rat
Authors: Wu Han‐Chiang , Lecain Eric , Chiappini Ilaria , Yang Ting‐Hua , Tran Ba Huy Patrice 
Published: December 2004

AbstractThe frequency organization in the inferior colliculus of neonatally‐deafened rats was investigated using electrical stimulation of the cochlea and immunoreactivity for Fos as a marker of neuronal activity. An electrode implanted either at the base or at the apex of the right cochlea delivered a unique 45‐min stimulation at two different level intensities and at two time points, i.e. either at 4 weeks or at 4 months. In 4‐week‐old rats stimulated at 5× threshold, a site‐for‐site organization was observed since basal or apical stimulation induced a strong labelling in the ventro‐medial or in the dorsolateral part of the left inferior colliculus, respectively. In 4‐month‐old rats, stimulation of the base induced an extremely weak Fos labelling without any specific location in the left inferior colliculus while stimulation of the apex induced a diffuse labelling with two discrete bands being distinguishable in the left inferior colliculus. In 4‐week‐old rats stimulated at 15× threshold, basal stimulation elicited a diffuse Fos‐like immunoreactivity in the left inferior colliculus while apical stimulation yielded a response restricted to the dorsal part of the left inferior colliculus. In 4‐month‐old rats, no response was detected in the left inferior colliculus after stimulation of the basal part of the cochlea. Stimulation of the apex could still induce a labelling in the dorsolateral left inferior colliculus. Thus, the inferior colliculus exhibits an adult‐like tonotopic organization early on independently of any acoustic stimulation. Prolonged absence of auditory input dramatically alters this organization in the inferior colliculus, especially for high frequencies. From a clinical standpoint, these results could argue for early implantation in deaf children.
Action of tachykinins in the rat hippocampus: modulation of inhibitory synaptic transmission
Authors: Ogier R. , Raggenbass M. 
Published: December 2004

AbstractSubstance P and other neuropeptides of the tachykinin family can powerfully excite CA1 hippocampal interneurons present in the CA1 region. In the present work we show that, by exciting hippocampal interneurons, tachykinins can indirectly inhibit pyramidal neurons. We found that tachykinins caused a decrease in the inhibitory synaptic current interval and an increase in the inhibitory synaptic current amplitude in almost all pyramidal neurons tested. This effect was tetrodotoxin sensitive. Tachykinins did not alter the frequency or amplitude of miniature inhibitory synaptic currents and were without effect on evoked inhibitory synaptic currents. Thus, these neuropeptides acted at the somatodendritic membrane of GABAergic interneurons, rather than at their axon terminals. The effect of substance P on spontaneous inhibitory synaptic currents could be mimicked by a selective agonist of NK1 receptors, but not by selective agonists of NK2 and NK3 receptors. It was suppressed by an NK1 receptor antagonist. In CA1 interneurons located in stratum radiatum, substance P generated a sustained tetrodotoxin‐insensitive inward current or induced membrane depolarization and action potential firing. This direct excitatory action was mediated by NK1 receptors. Current–voltage relationships indicate that the net tachykinin‐evoked current reversed in polarity at or near the K+ equilibrium potential, suggesting that a suppression of a resting K+ conductance was involved. By increasing the excitability of CA1 GABAergic interneurons, tachykinins can powerfully facilitate the inhibitory synaptic input to pyramidal neurons. This indirect inhibition could play a role in regulating short‐term and/or long‐term synaptic plasticity, promoting neuronal circuit synchronization or, in some physiopathological situations, influencing epileptogenesis.
Anticonvulsant pharmacology of voltage‐gated Na+ channels in hippocampal neurons of control and chronically epileptic rats
Authors: Remy Stefan , Urban Bernd W. , Elger Christian E. , Beck Heinz 
Published: December 2004

AbstractVoltage‐gated Na+ channels are a main target of many first‐line anticonvulsant drugs and their mechanism of action has been extensively investigated in cell lines and native neurons. Nevertheless, it is unknown whether the efficacy of these drugs might be altered following chronic epileptogenesis. We have, therefore, analysed the effects of phenytoin (100 µm), lamotrigine (100 µm) and valproate (600 µm) on Na+ currents in dissociated rat hippocampal granule neurons in the pilocarpine model of chronic epilepsy. In control animals, all three substances exhibited modest tonic blocking effects on Na+ channels in their resting state. These effects of phenytoin and lamotrigine were reduced (by 77 and 64%) in epileptic compared with control animals. Phenytoin and valproate caused a shift in the voltage dependence of fast inactivation in a hyperpolarizing direction, while all three substances shifted the voltage dependence of activation in a depolarizing direction. The anticonvulsant effects on Na+ channel voltage dependence proved to be similar in control and epileptic animals. The time course of fast recovery from inactivation was potently slowed by lamotrigine and phenytoin in control animals, while valproate had no effect. Interestingly, the effects of phenytoin on fast recovery from inactivation were significantly reduced in chronic epilepsy. Taken together, these results reveal that different anticonvulsant drugs may exert a distinct pattern of effects on native Na+ channels. Furthermore, the reduction of phenytoin and, to a less pronounced extent, lamotrigine effects in chronic epilepsy raises the possibility that reduced pharmacosensitivity of Na+ channels may contribute to the development of drug resistance.
Molecular cloning and expression regulation of PRG‐3, a new member of the plasticity‐related gene family
Authors: Savaskan Nicolai E. , Bräuer Anja U. , Nitsch Robert 
Published: December 2004

AbstractPhospholipid‐mediated signalling on neurons provokes diverse responses such as neurogenesis, pattern formation and neurite remodelling. We have recently uncovered a novel set of molecules in the mammalian brain, named plasticity‐related genes (PRGs), which mediate lipid phosphate phosphatase activity and provide evidence for their involvement in mechanisms of neuronal plasticity. Here, we report on a new member of the vertebrate‐specific PRG family, which we have named plasticity‐related gene‐3 (PRG‐3). PRG‐3 is heavily expressed in the brain and shows a specific expression pattern during brain development where PRG‐3 expression is found predominantly in neuronal cell layers and is already expressed at embryonic day 16. In the mature brain, strongest PRG‐3 expression occurs in the hippocampus and cerebellum. Overexcitation of neurons induced by kainic acid leads to a transient down‐regulation of PRG‐3. Furthermore, PRG‐3 is expressed on neurite extensions and promotes neurite growth and a spreading‐like cell body in neuronal cells and COS‐7 cells. In contrast to previously described members of the PRG family, PRG‐3 does not perform its function through enzymatic phospholipid degradation. In summary, our findings feature a new member of the PRG family which shows dynamic expression regulation during brain development and neuronal excitation.
Tissue plasminogen activator in primary afferents induces dorsal horn excitability and pain response after peripheral nerve injury
Authors: Yamanaka Hiroki , Obata Koichi , Fukuoka Tetsuo , Dai Yi , Kobayashi Kimiko , Tokunaga Atsushi , Noguchi Koichi 
Published: December 2004

AbstractThe extracellular protease cascade of plasminogen activators and plasminogen are known to regulate neuronal plasticity and extracellular matrix modification, and to be important factors involved in producing long‐term potentiation in the CNS. The purpose of this study is to examine the expression of plasminogen activators in primary afferents and its role in nociceptive pathways after peripheral nerve injury. We found the induction of mRNAs for tissue type plasminogen activator (tPA) and urokinase plasminogen activator (uPA) in the rat dorsal root ganglia following sciatic nerve transection. Immunoreactivity for tPA was increased in laminae I and II of the dorsal horn and, importantly, the increase in proteolytic activity mediated by tPA was observed in the same area. As neither immunoreactivity for uPA nor uPA‐mediated proteolysis was observed, we further examined the effects of tPA on dorsal horn excitability and neuropathic pain behaviour. Intrathecal injection of a specific inhibitor of tPA decreased electrical stimulation‐induced Fos expression in dorsal horn neurons following axotomy, and also prevented the development of thermal hyperalgesia following partial sciatic nerve ligation. These findings suggest that the increased tPA in the dorsal horn due to mRNA expression in the dorsal root ganglia increases the dorsal horn excitability and has an important role in pain behaviour after peripheral nerve injury. The tPA‐mediated hypersensitivity in dorsal horn neurons may be a novel molecular mechanism of neuropathic pain.
Richness dependence and climatic forcing as regulating processes of coastal fish‐species richness
Authors: Lekve Kyrre , Stenseth Nils Chr. , Johansen Rune , Lingjærde Ole Chr. , Gjøsæter Jakob 
Published: December 2004

AbstractThe maintenance of species diversity is influenced by processes originating both within and outside the ecological community of concern. Along the Norwegian Skagerrak coast, the number of fish species displays variability around a rather stable long‐time average. Using a mechanistically based first‐order autoregressive model with environmental forcing for the species number, we demonstrate for this system the presence of richness‐dependent regulation of species diversity. We explicitly model the niche space as a carrying capacity of species diversity and the intrinsic community feedback as a richness‐dependent regulation. Wind stress, temperature and the North Atlantic Oscillation (NAO) are used as environmental variables. This general and flexible model successfully captures the community dynamics of fish in the coastal areas of the Norwegian Skagerrak coast and thereby demonstrates the validity of developing general models of biodiversity patterns.
Selenium Deficiency Associated with Cardiomyopathy: A Complication of the Ketogenic Diet
Authors: Bergqvist A. G. Christina , Chee Claire M. , Lutchka Lisa , Rychik Jack , Stallings Virginia A. 
Published: December 2004

Summary:  Purpose: The ketogenic diet (KD) is an efficacious treatment for intractable epilepsy, associated with infrequent side effects. The KD is known to be deficient in most vitamins and minerals and may be deficient in trace minerals. We report biochemical selenium deficiency in nine patients on the KD, including one who developed cardiomyopathy.Methods: A whole‐blood selenium level was obtained on the symptomatic patient after noting the patient's poor appearance on physical examination. Children already treated and children beginning the KD were then evaluated prospectively for selenium status by measuring whole‐blood or serum selenium as part of routine laboratory evaluation every 3 months.Results: The index case had no detectable whole‐blood selenium. Cardiac physical examination and ECG were normal, but the echocardiogram revealed cardiomyopathy. Thirty‐nine additional children had the selenium status evaluated. Eight had selenium levels below the normal range (six initially, and two developed low selenium levels on serial testing). They were referred for cardiology evaluations, which were normal. Selenium supplementation improved levels in all children. Low levels were seen in some children after only a few months of treatment.Conclusions: The nutrient adequacy of the currently used KD has not been fully evaluated. The nutrient content of KD with usual supplements may not meet Recommended Dietary Allowances (RDA) for selenium and may not provide other trace minerals in adequate amounts. At our center, selenium deficiency was found in 20% of the patients evaluated. Screening for selenium deficiency is suggested if the patient KD regimen does not meet ≥75% of the RDA or if the child is symptomatic. Nutrient supplementation should provide adequate trace elements for children treated with the KD. The KD requires close monitoring of the overall nutritional status.
A Kindling Model of Pharmacoresistant Temporal Lobe Epilepsy in Sprague–Dawley Rats Induced by Coriaria Lactone and Its Possible Mechanism
Authors: Wang Ying , Zhou Dong , Wang Bing , Li Huaisu , Chai Huixia , Zhou Qiao , Zhang Shangfu , Stefan Hermann 
Published: December 2004

Summary:  Purpose: The aim of this study was to develop a new animal model of pharmacoresistant temporal lobe epilepsy (TLE) by repeated intramuscular injection of Coriaria lactone (CL) at subthreshold dosages and to explore the mechanisms that might be involved.Methods: Healthy male Sprague–Dawley rats (n = 160) were randomized into four groups during the kindling process: three groups (n = 50 for each group) received CL injection at subthreshold dosages (1.25, 1.5, and 1.75 mg/kg, respectively), and ten received normal saline (NS) injection as a control group. The maximal human adult dosage of carbamazepine (CBZ), valproate (VPA), and phenytoin (PHT) was administered as monotherapy to different groups of kindled rats for 1 month (n = 20 for each group). Changes in EEG recording, seizure number, intensity (expressed as grade 1–5 according to Racine stage), and duration, including spontaneous seizures during different interventions, were compared. The expression of P‐170, a multiple drug resistance gene (MDR1) encoding P‐glycoprotein, was measured in brain samples from different groups of experimental rats by using an image analysis and measurement system (ImagePro‐Plus 4.0).Results: A total of 70 (46.7%) rats were fully kindled with a median of 15 (seven to 20) CL injections. Electrocorticogram (ECoG) including hippocampal (EHG) monitoring revealed the temporal lobe origins of epileptiform potentials, which were consistent with the behavioral changes observed. Spontaneous seizures occurred with frequency and diurnal patterns similar to those of human TLE. The antiepileptic drugs (AEDs) tested lacked a satisfactory seizure control. The maximal P‐170 expression was in the kindled rats with AED treatment; the next highest was in the kindled rats without AED intervention. Nonkindled SD rats with CL injection also had increased P‐170 expression compared with control SD rats.Conclusions: The study provided a simple and stable animal TLE kindling model with pharmacoresistant properties. The pharmacoresistance observed in the kindled rats to CBZ, VPA, and PHT at maximal human adult dosages together with the increased P‐170 expression was a distinct feature of this model. This model might be used in further investigations of the mechanisms involved in pharmacoresistant TLE and for developing new AEDs.
Posttraumatic Epilepsy: Neuroradiologic and Neuropsychological Assessment of Long‐term Outcome
Authors: Mazzini Letizia , Cossa Federico Maria , Angelino Elisabetta , Campini Riccardo , Pastore Ilaria , Monaco Francesco 
Published: December 2004

Summary:   Purpose: We sought to detect the incidence and the risk factors of posttraumatic epilepsy (PTE) in rehabilitation patients; to define the influence of PTE for late clinical and functional outcome; and to assess the cognitive and behavioral features of the patients with PTE.Methods: Patients were examined with (a) cognitive and behavioral examinations, which included a clinical interview and psychometric tests performed by an expert clinical psychologist; (b) single‐photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI); and (c) functional evaluation including the Glasgow Outcome Scale (GOS) and the Functional Independence Measure (FIM).Results: Of the 143 patients examined in this study, in 27 (19%), seizures developed after a mean time from trauma of 11.9 ± 8.6 months. The occurrence of PTE was significantly correlated with the hypoperfusion in temporal lobes (p < 0.004), the degree of hydrocephalus (p < 0.04), the evidence of intracerebral hematoma (p < 0.01), and operative brain injury (p < 0.001). Patients with epilepsy showed a significantly higher incidence of personality disorders than did patients without epilepsy. The disinhibited behavior, irritability, and agitated and aggressive behavior were significantly more frequent and severe in PTE patients. The psychometric tests intended to explore memory, language, intelligence, attention, and spatial cognition did not show any significant difference between those with and without epilepsy. PTE also was significantly correlated with a worse functional outcome 1 year after the trauma.Conclusions: The degrees of hydrocephalus and of hypoperfusion in the temporal lobes are significant risk factors for late PTE. Another main finding of our study is the absence of influence of epilepsy on cognitive disorders; its influence on neurobehavioral disorders and functional outcome is discussed.
Neocortical Temporal FDG‐PET Hypometabolism Correlates with Temporal Lobe Atrophy in Hippocampal Sclerosis Associated with Microscopic Cortical Dysplasia
Authors: Diehl Beate , LaPresto Eric , Najm Imad , Raja Shanker , Rona Sabine , Babb Thomas , Ying Zhong , Bingaman William , Lüders Hans O. , Ruggieri Paul 
Published: December 2004

Summary:  Purpose: Medically intractable temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS), with or without cortical dysplasia (CD), is associated with atrophy of the hippocampal formation and regional fluorodeoxyglucose positron‐emission tomography (FDG‐PET) hypometabolism. The relation between areas of functional and structural abnormalities is not well understood. We investigate the relation between FDG‐PET metabolism and temporal lobe (TL) and hippocampal atrophy in patients with histologically proven isolated HS and HS associated with CD.Methods: Twenty‐three patients underwent en bloc resection of the mesial and anterolateral neocortical structures. Ten patients were diagnosed with isolated HS; 13 patients had associated microscopic CD. Temporal lobe volumes (TLVs) and hippocampal volumes were measured. Magnetic resonance imaging (MRI) and PET were co‐registered, and regions of interest (ROIs) determined as gray matter of the mesial, lateral, and anterior temporal lobe.Results: All patients (HS with or without CD) had significant ipsilateral PET hypometabolism in all three regions studied (p < 0.0001). In patients with isolated HS, the most prominent hypometabolism was in the anterior and mesial temporal lobe, whereas in dual pathology, it was in the lateral temporal lobe. TLVs and hippocampal volumes were significantly smaller on the epileptogenic side (p < 0.05). The PET asymmetries ipsilateral/contralateral to the epileptogenic zone and TLV asymmetries correlated significantly for the anterior and lateral temporal lobes (p < 0.05) in the HS+CD group, but not in the isolated HS group. Mesial temporal hypometabolism was not significantly different between the two groups.Conclusions: Temporal neocortical microscopic CD with concurrent HS is associated with more prominent lateral temporal metabolic dysfunction compared with isolated HS in TL atrophy. Further studies are needed to confirm these findings and correlate the PET hypometabolic patterns with outcome data in patients operated on for HS with or without CD.
Mapping of the Rat's Motor Area after Hemispherectomy: The Hemispheres as Potentially Independent Motor Brains
Authors: Machado André G. G. , Shoji Alexandre , Ballester Gerson , Marino Raul 
Published: December 2004

Summary:  Purpose: The remarkable motor recovery observed after hemispherectomy in patients and experimental animals has puzzled investigators, as it defies classic jacksonian neurology. Several mechanisms for this phenomenon have been considered, such as neuronal sprouting to subcortical structures, neurochemical changes, and cerebellar diaschisis. The spared hemisphere may, however, play a crucial part in this functional recovery.Methods: In this study, seven Wistar rats were submitted to right hemisphere motor area mapping. In the same anesthetic time, a left microsurgical hemispherectomy was performed, and the animal allowed to recover for 2 weeks. After then, the right hemisphere was again stimulated for its motor area.Results: Four rats had, after 2 weeks of observation, bilateral body movements with stimulation of only the right hemisphere. The same segments on both sides had symmetric and simultaneous movements.Conclusions: The results suggest that each motor area has the latent capacity to control motricity bilaterally, and that such capacity is brought into function after removal of the opposite hemisphere. The same neuronal population that gives afference to one segment contralaterally seems to give afference to the same segment ipsilaterally.