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1.
Purpose: To determine whether changes in gray matter volume (GMV) differ according to the affected side in mesial temporal lobe epilepsy/hippocampal sclerosis (MTLE/HS) syndrome, and moreover to test the hypothesis of more pronounced structural changes in right‐sided MTLE/HS. This hypothesis (especially that the contralateral thalamus is more affected in right‐sided MTLE/HS) arose from the results of our recent study, wherein more expressed structural and functional changes were observed in a small sample of patients with right‐sided MTLE/HS ( Brázdil et al., 2009 ). Methods: Twenty patients with left‐sided and 20 with right‐sided MTLE/HS and 40 sex‐ and age‐matched healthy controls were included in the study. Voxel‐based morphometry (VBM) with a modulation step was applied to magnetic resonance imaging (MRI) brain images. Statistical parametric maps were used to compare structural changes between patients and controls separately for the left‐ and right‐sided MTLE/HS subgroups. We also compared the local GMV of the brain structures (insula and thalamus) between the subgroups of patients. Results: In the subgroup with right‐sided MTLE/HS, a reduction of GMV was detected in the mesiotemporal structures and the ipsilateral thalamus (as in left‐sided MTLE/HS), but also notably in the ipsilateral insula and contralateral thalamus. A statistical analysis revealed a significantly more extensive reduction of GMV in the ipsilateral/contralateral insula and the contralateral thalamus in the subgroup with right‐sided compared to left‐sided MTLE/HS. Conclusion: We found asymmetrical morphologic changes in patients with left‐ and right‐sided MTLE/HS syndrome (more pronounced in right‐sided MTLE/HS). These differences could be theoretically explained by different neuronal networks and pathophysiologic changes in temporolimbic structures. 相似文献
2.
Mesial temporal lobe epilepsy with hippocampal sclerosis is infrequently associated with neuronal autoantibodies
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Adaucto W. Nóbrega‐Jr Christian P. Gregory Rachel Schlindwein‐Zanini Fabricio de Souza Neves Peter Wolf Roger Walz Mario Steindel Katia Lin 《Epilepsia》2018,59(9):e152-e156
Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE‐HS) is characterized by its well‐defined clinical profile. Limbic encephalitis is increasingly recognized as a possible etiology of adult‐onset MTLE‐HS, and neuronal autoantibodies have been detected in patients even without previous signs of encephalitis. The aim of this study is to analyze the frequency of specific autoantibodies in patients with MTLE‐HS. A case‐control study was carried out with 100 patients with MTLE‐HS and 50 healthy controls. Sera samples from subjects were tested by indirect immunofluorescence assay for detection of anti‐N‐methyl‐d ‐aspartate receptor (NMDA‐R), anti‐contactin‐associated protein‐like 2 (CASPR2), anti‐leucine‐rich glioma inactivated 1 (LGI1), anti‐gamma aminobutyric acid B receptor (GABA‐B‐R), anti‐alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid 1 and 2 receptors (AMPA‐1‐R and AMPA‐2‐R), and enzyme‐linked immunosorbent assay for detection of anti‐glutamic acid decarboxylase 65 (GAD65). Mean age of patients and controls was 41.2 vs 42 years, and 55% vs 56% were female. Mean duration of epilepsy was 27.2 years. No neuronal autoantibodies were found in either group, except for anti‐GAD65 in 3 patients and 2 controls. This study adds to the mounting evidence that, in Brazilian patients, MTLE‐HS without signs and symptoms of autoimmune encephalitis may be infrequently associated with these autoantibodies. Differences regarding accuracy of used methodologies for autoantibody detection and genetic and environmental characteristics are discussed. Further works with different methodologies tested simultaneously in different populations may help clarify the incongruent study results about autoantibodies in MTLE‐HS. 相似文献
3.
Activation of mTOR signaling pathway is secondary to neuronal excitability in a mouse model of mesio‐temporal lobe epilepsy
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Ayako Shima Naoki Nitta Fumio Suzuki Anne‐Marie Laharie Kazuhiko Nozaki Antoine Depaulis 《The European journal of neuroscience》2015,41(7):976-988
Recent studies in animal models have suggested that the mammalian target of rapamycin (mTOR) signaling pathway is involved in several features of mesio‐temporal lobe epilepsy (MTLE), and that its inhibition could have therapeutic interests. However, it remains controversial whether mTOR activation is the cause or the consequence of MTLE. We previously showed in a mouse model of MTLE associated with hippocampal sclerosis that increased neuronal excitability and brain‐derived neurotrophic factor (BDNF) overexpression contribute to the development of morphological features of this form of epilepsy. Here, we addressed whether mTOR activation promotes MTLE epileptogenesis via increasing neuronal excitability and/or BDNF expression or rather mediates neuroplasticity associated with hippocampal sclerosis. In mice injected intrahippocampally with kainate (1 nmol), we showed a biphasic increase of phospho‐S6 (p‐S6) ribosomal protein expression, the downstream product of the mTOR signaling pathway, in the dispersed granule cell layer (GCL) of the dentate gyrus with a second phase lasting up to 6 months. Chronic treatment with rapamycin suppressed p‐S6 expression, granule cell dispersion and mossy fiber sprouting, but did not reduce cell loss, BDNF overexpression, glutamic acid decarboxylase (GAD)67 expression or the development of hippocampal paroxysmal discharges. Neuronal inhibition by midazolam (2 × 10 mg/kg, i.p.) abolished the increased expression of p‐S6 in the dispersed GCL. Our data suggest that activation of the mTOR signaling pathway results from the increased neuronal excitation that develops in the GCL and may contribute to MTLE morphological changes. However, these data do not support the role of this pathway in the development of MTLE or its inhibition as a therapy for this form of epilepsy. 相似文献
4.
Michael L. Brines Sanjoy Sundaresan Dennis D. Spencer Nihal C. de Lanerolle 《The European journal of neuroscience》1997,9(10):2035-2044
Medically intractable temporal lobe epilepsy is a common disease typically associated with hippocampal damage (sclerosis) and synaptic remodelling. These changes could include increased glutamate receptor expression, enhancing excitability and the potential for neuronal injury. We directly assessed this hypothesis using quantitative in vitro receptor autoradiography to determine the densities of glutamate-, NMDA-, quisqualateh-amino-3-hydroxy-5-methyl-isoxazoleproprionic acid (AMPA)- and kainic acid-preferring binding sites in surgically removed hippocampi from patients with mesial temporal lobe epilepsy (sclerosis; MTLE) and patients with mass-associated temporal lobe epilepsy (no sclerosis: MaTLE), compared with autopsy material. Neuronal cell counts and in situ total protein densities were also obtained. In general, MaTLE and autopsy binding densities were indistinguishable. In contrast, some regions of MTLE hippocampi exhibited decreased receptor densities, with a corresponding loss of protein. In the hilus and CA1, however, ligand binding densities did not differ from the comparison groups in spite of markedly reduced protein content, consistent with increased glutamate receptor density. Kainate-preferring sites were distributed differently from the other glutamate subtypes and were uniformly decreased throughout the MTLE hippocampus, except for a unique expression within the outer dentate molecular layer. Along with increased NMDA and AMPA receptor densities in the hilus and CA1, this distinctive population of kainate receptors establishes that increased glutamate receptor expression is a feature of the remodelled MTLE hippocampus. These observations suggest that enhanced sensitivity to glutamate may be an important element in the pathophysiology of temporal lobe epilepsy. 相似文献
5.
h channel-dependent deficit of theta oscillation resonance and phase shift in temporal lobe epilepsy
Batrice Marcelin Laëtitia Chauvire Albert Becker Michele Migliore Monique Esclapez Christophe Bernard 《Neurobiology of disease》2009,33(3):436-447
Ih tunes hippocampal CA1 pyramidal cell dendrites to optimally respond to theta inputs (4–12 Hz), and provides a negative time delay to theta inputs. Decreased Ih activity, as seen in experimental temporal lobe epilepsy (TLE), could significantly alter the response of dendrites to theta inputs. Here we report a progressive erosion of theta resonance and phase lead in pyramidal cell dendrites during epileptogenesis in a rat model of TLE. These alterations were due to decreased Ih availability, via a decline in HCN1/HCN2 subunit expression resulting in decreased h currents, and altered kinetics of the residual channels. This acquired HCN channelopathy thus compromises temporal coding and tuning to theta inputs in pyramidal cell dendrites. Decreased theta resonance in vitro also correlated with a reduction in theta frequency and power in vivo. We suggest that the neuronal/circuitry changes associated with TLE, including altered Ih-dependent inductive mechanisms, can disrupt hippocampal theta function. 相似文献
6.
Susan Tomlinson FRACP David Burke MD DSc Mike Hanna MD FRCP Martin Koltzenburg MD FRCP Hugh Bostock PhD 《Muscle & nerve》2010,41(2):247-256
The “Trond” protocol of nerve excitability tests has been used widely to assess axonal function in peripheral nerve. In this study, the routine Trond protocol was expanded to refine assessment of cAMP‐dependent, hyperpolarization‐activated current (Ih) activity. Ih activity is generated by hyperpolarization‐activated, cyclic nucleotide–modulated (HCN) channels in response to hyperpolarization. It limits activity‐dependent hyperpolarization, contributes to neuronal automaticity, and is implicated in chronic pain states. Published data regarding Ih activity in motor nerve are scant. We used additional strong, prolonged hyperpolarizing conditioning stimuli in the threshold electrotonus component of the Trond protocol to demonstrate the time‐course of activation of Ih in motor axons. Fifteen healthy volunteers were tested on four occasions during 1 week. Ih action was revealed in the threshold electrotonus by the limiting and often reversal, after about 100 ms, of the threshold increase caused by strong hyperpolarizing currents. Statistical analysis by repeated‐measures analysis of variance enabled confidence limits to be established for variation between subjects and within subjects. The results demonstrate that, of all the excitability parameters, those dependent on Ih were the most characteristic of an individual, because variance between subjects was more than four times the variance within subjects. This study demonstrates a reliable method for in vivo assessment of Ih, and also serves to document the normal variability in nerve excitability properties within subjects. Muscle Nerve, 2010 相似文献
7.
Arne Battefeld Claudia Bierwirth Ying Chuan Li Lennart Barthel Tanja Velmans Ulf Strauss 《Journal of neuroscience research》2010,88(14):3067-3078
Hyperpolarization‐activated cyclic nucleotide‐gated ion channels (HCN) are key determinants of CNS functions. Here we describe an increase in hyperpolarization‐activated current (Ih) at the beginning of whole‐cell recordings in rat layer 5 cortical neurons. For a closer investigation of this Ih increase, we overexpressed the predominant layer 5 rat subunit HCN1 in HEK293 cells. We characterized the resulting Ih in the cell‐attached and whole‐cell configurations. Breaking into whole‐cell configuration led to about a 30% enhancement of rat HCN1‐mediated Ih accompanied by a depolarizing shift in voltage dependence and an accelerated time course of activation. This current enhancement is not species specific; for human HCN1, the current similarly increases in amount and kinetics. Although the changes were bound to cytosolic solution exchange, they were independent of cAMP, ATP, GTP, and the phosphate group donor phosphocreatine. Together, these data provide a characterization of heterologous expression of rat HCN1 and suggest that cytosolic contents suppress Ih. Such a mechanism might constitute a reserve in h‐channel function in vivo. © 2010 Wiley‐Liss, Inc. 相似文献
8.
Stephan Wierschke Thomas‐Nicolas Lehmann Christoph Dehnicke Peter Horn Robert Nitsch Rudolf A. Deisz 《Epilepsia》2010,51(3):404-414
Purpose: Hyperpolarization‐activated cation currents (IH) play a pivotal role in the control of neuronal excitability. In animal models of epilepsy both increases and decreases of IH have been reported. We, therefore, characterized properties of IH in human epileptogenic neocortex. Methods: Layer II/III neurons in slices from epilepsy surgery tissues and rat cortex were investigated with whole‐cell patch‐clamp recordings. Results: A total of 484 neurons from 96 temporal lobe epilepsy (TLE) tissues and 32 neurons from 8 frontal lobe epilepsy (FLE) tissues were recorded. Voltage‐clamp recordings revealed on hyperpolarizing command steps two time‐ and voltage‐dependent inward currents, namely a fast, Ba2+‐sensitive current (KIR) and a slowly activating current, namely consisting of two kinetically distinct components sensitive to the established IH blocker ZD7288. Only, the fast component (IH(fast)) of TLE neurons was on average smaller and activated more slowly (density 2.7 ± 1.6 pA/pF; tau 38.4 ± 34.0 ms) than in FLE neurons (4.7 ± 2.3 pA/pF; 16.6 ± 7.9 ms; p < 0.001 for both). Within the TLE tissues the IH(fast) density (averaged per patient) was smaller in cases with numerous annual grand mal seizures (GM; 2.2 ± 0.6 pA/pF) compared to those with few GM (2.8 ± 1.0 pA/pF; p = 0.0184). A similar difference was obtained in the case of complex partial seizures (CPS; many CPS 2.2 ± 0.6 pA/pF; few CPS 2.9 ± 1.0 pA/pF, p = 0.0037). Discussion: The biophysical properties of IH in cortices from TLE, FLE, and rat tissue suggest a deficit of HCN1 subunits in the human epileptogenic neocortex, which in turn may increase excitability and probability of seizure activity. 相似文献
9.
10.
Bina Santoro Janet Y. Lee Dario J. Englot Sandra Gildersleeve Rebecca A. Piskorowski Steven A. Siegelbaum Melodie R. Winawer Hal Blumenfeld 《Epilepsia》2010,51(8):1624-1627
Persistent down‐regulation in the expression of the hyperpolarization‐activated HCN1 cation channel, a key determinant of intrinsic neuronal excitability, has been observed in febrile seizure, temporal lobe epilepsy, and generalized epilepsy animal models, as well as in patients with epilepsy. However, the role and importance of HCN1 down‐regulation for seizure activity is unclear. To address this question we determined the susceptibility of mice with either a general or forebrain‐restricted deletion of HCN1 to limbic seizure induction by amygdala kindling or pilocarpine administration. Loss of HCN1 expression in both mouse lines is associated with higher seizure severity and higher seizure‐related mortality, independent of the seizure‐induction method used. Therefore, down‐regulation of HCN1 associated with human epilepsy and rodent models may be a contributing factor in seizure behavior. 相似文献
11.
Maria Thom 《Neuropathology and applied neurobiology》2014,40(5):520-543
Hippocampal sclerosis (HS) is a common pathology encountered in mesial temporal lobe epilepsy (MTLE) as well as other epilepsy syndromes and in both surgical and post‐mortem practice. The 2013 International League Against Epilepsy (ILAE) classification segregates HS into typical (type 1) and atypical (type 2 and 3) groups, based on the histological patterns of subfield neuronal loss and gliosis. In addition, granule cell reorganization and alterations of interneuronal populations, neuropeptide fibre networks and mossy fibre sprouting are distinctive features of HS associated with epilepsies; they can be useful diagnostic aids to discriminate from other causes of HS, as well as highlighting potential mechanisms of hippocampal epileptogenesis. The cause of HS remains elusive and may be multifactorial; the contribution of febrile seizures, genetic susceptibility, inflammatory and neurodevelopmental factors are discussed. Post‐mortem based research in HS, as an addition to studies on surgical samples, has the added advantage of enabling the study of the wider network changes associated with HS, the long‐term effects of epilepsy on the pathology and associated comorbidities. It is likely that HS is heterogeneous in aspects of its cause, epileptogenetic mechanisms, network alterations and response to medical and surgical treatments. Future neuropathological studies will contribute to better recognition and understanding of these clinical and patho‐aetiological subtypes of HS. 相似文献
12.
Among epilepsy‐associated non‐neoplastic lesions, mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE‐HS) and malformation of cortical development (MCD), including focal cortical dysplasia (FCD), are the two most frequent causes of drug‐resistant focal epilepsies, constituting about 50% of all surgical pathology of epilepsy. Several distinct histological patterns have been historically recognized in both HS and FCD, and several studies have tried to perform clinicopathological correlations. However, results have been controversial, particularly in terms of post‐surgical seizure outcome. Recently, the International League Against Epilepsy constituted a Task Forces of Neuropathology and FCD within the Commission on Diagnostic Methods, to establish an international consensus of histological classification of HS and FCD, respectively, based on agreement with the recognition of the importance of defining a histopathological classification system that reliably has some clinicopathological correlation. Such consensus classifications are likely to facilitate future clinicopathological studies. Meanwhile, we reviewed the neuropathology of 41 surgical cases of mTLE, and confirmed three type/patterns of HS along with no HS, based on the qualitative evaluation of the distribution and severity of neuronal loss and gliosis within hippocampal formation, that is, HS type 1 (61%) equivalent to “classical” Ammon's horn sclerosis, HS type 2 (2%) representing CA1 sclerosis, HS type 3 (17%) equivalent to end folium sclerosis, and no HS (19%). Furthermore, we performed a neuropathological comparative study on mTLE‐HS and dementia‐associated HS (d‐HS) in the elderly, and confirmed that neuropathological features differ between mTLE‐HS and d‐HS in the distribution of hippocampal neuronal loss and gliosis, morphology of reactive astrocytes and their protein expression, and presence of concomitant neurodegenerative changes, particularly Alzheimer type and TDP‐43 pathologies. These differences may account, at least in part, for the difference in pathogenesis and epileptogenicity of HS in mTLE and senile dementia. However, the etiology and pathogenesis of most epileptogenic lesions are yet to be elucidated. 相似文献
13.
Menzler K Thiel P Hermsen A Chen X Benes L Miller D Sure U Knake S Rosenow F 《Epilepsia》2011,52(4):707-711
Purpose: The recent “Report of the ILAE Commission on Classification and Terminology” recommends an epilepsy classification that gives more emphasis to the underlying structural or metabolic cause rather than to the localization of the epileptogenic zone. The aim of the present study was to investigate differences in clinical features, treatment response, and prognosis in patients with mesial temporal lobe epilepsy (MTLE) caused by hippocampal sclerosis (MTLE‐HS) or singular mesiotemporal cavernomas (MTLE‐C) in order to evaluate the impact of underlying pathology on the course of the disease while controlling for localization. Methods: Age at onset, age at surgery, seizure frequency and semiology, pharmacoresistance, psychiatric comorbidities, memory deficits, or initial precipitating insults (e.g., febrile seizures, traumatic brain injury, infection of the central nervous system, birth complications) as well as postoperative outcome were compared in eleven patients with MTLE‐C and 33 patients with MTLE‐HS using nonparametric statistical methods. Key Findings: The postoperative outcome was significantly better in patients with MTLE‐C, even after controlling for preoperative epilepsy duration. Patients with MTLE‐HS more frequently were drug resistant (88% vs. 36%) and more often presented with an initial precipitating insult (70% vs. 27%) and with automotor seizures (79% vs. 46%). Significance: The results suggest that patients with MTLE‐C show a more favorable postoperative outcome, supporting the commission’s suggestion to put more emphasis on the underlying cause in future epilepsy classifications. 相似文献
14.
Long‐term high‐intensity sound stimulation inhibits h current (Ih) in CA1 pyramidal neurons
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Alexandra Olimpio Siqueira Cunha Cesar Celis Ceballos Junia Lara de Deus Ricardo Maurício Leão 《The European journal of neuroscience》2018,47(11):1401-1413
Afferent neurotransmission to hippocampal pyramidal cells can lead to long‐term changes to their intrinsic membrane properties and affect many ion currents. One of the most plastic neuronal currents is the hyperpolarization‐activated cationic current (Ih), which changes in CA1 pyramidal cells in response to many types of physiological and pathological processes, including auditory stimulation. Recently, we demonstrated that long‐term potentiation (LTP) in rat hippocampal Schaffer‐CA1 synapses is depressed by high‐intensity sound stimulation. Here, we investigated whether a long‐term high‐intensity sound stimulation could affect intrinsic membrane properties of rat CA1 pyramidal neurons. Our results showed that Ih is depressed by long‐term high‐intensity sound exposure (1 min of 110 dB sound, applied two times per day for 10 days). This resulted in a decreased resting membrane potential, increased membrane input resistance and time constant, and decreased action potential threshold. In addition, CA1 pyramidal neurons from sound‐exposed animals fired more action potentials than neurons from control animals; however, this effect was not caused by a decreased Ih. On the other hand, a single episode (1 min) of 110 dB sound stimulation which also inhibits hippocampal LTP did not affect Ih and firing in pyramidal neurons, suggesting that effects on Ih are long‐term responses to high‐intensity sound exposure. Our results show that prolonged exposure to high‐intensity sound affects intrinsic membrane properties of hippocampal pyramidal neurons, mainly by decreasing the amplitude of Ih. 相似文献
15.
Fernando Cendes Americo C. Sakamoto Roberto Spreafico William Bingaman Albert J. Becker 《Acta neuropathologica》2014,128(1):21-37
Hippocampal sclerosis (HS) is considered the most frequent neuropathological finding in patients with mesial temporal lobe epilepsy (MTLE). Hippocampal specimens of pharmacoresistant MTLE patients that underwent epilepsy surgery for seizure control reveal the characteristic pattern of segmental neuronal cell loss and concomitant astrogliosis. However, classification issues of hippocampal lesion patterns have been a matter of intense debate. International consensus classification has only recently provided significant progress for comparisons of neurosurgical and clinic-pathological series between different centers. The respective four-tiered classification system of the International League Against Epilepsy subdivides HS into three types and includes a term of “gliosis only, no-HS”. Future studies will be necessary to investigate whether each of these subtypes of HS may be related to different etiological factors or with postoperative memory and seizure outcome. Molecular studies have provided potential deeper insights into the pathogenesis of HS and MTLE on the basis of epilepsy-surgical hippocampal specimens and corresponding animal models. These include channelopathies, activation of NMDA receptors, and other conditions related to Ca2+ influx into neurons, the imbalance of Ca2+—binding proteins, acquired channelopathies that increase neuronal excitability, paraneoplastic and non-paraneoplastic inflammatory events, and epigenetic regulation promoting or facilitating hippocampal epileptogenesis. Genetic predisposition for HS is clearly suggested by the high incidence of family history in patients with HS, and by familial MTLE with HS. So far, it is clear that HS is multifactorial and there is no individual pathogenic factor either necessary or sufficient to generate this intriguing histopathological condition. The obvious variety of pathogenetic combinations underlying HS may explain the multitude of clinical presentations, different responses to clinical and surgical treatment. We believe that the stratification of neuropathological patterns can help to characterize specific clinic-pathological entities and predict the postsurgical seizure control in an improved fashion. 相似文献
16.
Subcellular reorganization and altered phosphorylation of the astrocytic gap junction protein connexin43 in human and experimental temporal lobe epilepsy
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Tushar Deshpande Tingsong Li Michel K. Herde Albert Becker Hartmut Vatter Martin K. Schwarz Christian Henneberger Christian Steinhäuser Peter Bedner 《Glia》2017,65(11):1809-1820
17.
Purpose: Hypoxia‐inducible factor‐1α (HIF‐1α) is involved in critical aspects of cell survival in response to hypoxia and regulates vascular endothelial growth factor (VEGF) expression. Previous experimental and human studies in epilepsy show up‐regulation of VEGF following seizures, although expression of HIF‐1α as its potential regulator has not been explored. We used a postmortem (PM) series from patients with epilepsy and hippocampal sclerosis (HS) to investigate patterns of expression of HIF‐1α and VEGF and their potential contribution to neuroprotection. Method: In 33 PMs (17 cases with unilateral HS, 3 with bilateral HS, 3 with No‐HS, and 10 controls), we quantified neuronal immunolabeling for HIF‐1α and VEGF in hippocampal subfields. Key Findings: HIF‐1α‐ and VEGF‐immunopositive hippocampal neurones were observed in HS, No‐HS, and also in control cases; there was no significant difference in overall labeling between epilepsy cases and controls. In positive cases, HIF‐1α and VEGF neuronal labeling localized primarily in CA1, CA4, and CA3 subfields in all groups; significantly more positive neurons were seen in the entorhinal cortex in epilepsy cases (p < 0.05). Labeling lateralized to the side of sclerosis in unilateral HS cases, with significant differences between hemispheres (p < 0.05). There was a trend for high HIF‐1α labeling scores in patients with Dravet syndrome without HS and sudden unexpected death in epilepsy (SUDEP) cases, and lower scores with long seizure‐free periods prior to death. Hippocampal HIF‐1α and VEGF labeling showed a significant correlation. There was neuronal colocalization of HIF‐1α and VEGF. Significance: Regional expression patterns are in keeping with seizure‐related activation of HIF‐1α and VEGF. The prominent expression in non‐HS cases could support an overall neuroprotective effect. Correlation between HIF‐1α and VEGF neuronal immunolabeling supports HIF‐1α–mediated induction of VEGF in epilepsy. 相似文献
18.
Macrophages are critical cells in mediating the pathology of neurodegenerative disorders and enhancement of neuronal outward potassium (K+) current has implicated in neuronal apoptosis. To understand how activated macrophages induce neuronal dysfunction and injury, we studied the effects of lipopolysaccharide (LPS)‐stimulated human monocytes‐derived macrophage (MDM) on neuronal outward delayed rectifier K+ current (IK) and resultant change on neuronal viability in primary rat hippocampal neuronal culture. Bath application of LPS‐stimulated MDM‐conditioned media (MCM) enhanced neuronal IK in a concentration‐dependentmanner, whereas non‐stimulated MCM failed to alter neuronal IK. The enhancement of neuronal IK was repeated in a macrophage‐neuronal co‐culture system. The link of stimulated MCM (MCM(+))‐associated enhancement of IK to MCM(+)‐induced neuronal injury, as detected by PI/DAPI (propidium iodide/4′,6‐diamidino‐2‐phenylindol) staining and MTT assay, was demonstrated by experimental results showing that addition of IK blocker tetraethylammonium to the culture protected hippocampal neurons from MCM(+)‐associated challenge. Further investigation revealed elevated levels of Kv 1.3 and Kv 1.5 channel expression in hippocampal neurons after addition of MCM(+) to the culture. These results suggest that during brain inflammation macrophages, through their capacity of releasing bioactive molecules, induce neuronal injury by enhancing neuronal IK and that modulation of Kv channels is a new approach to neuroprotection. © 2009 Wiley‐Liss, Inc. 相似文献
19.
Catarino CB Kasperavičiūtė D Thom M Cavalleri GL Martinian L Heinzen EL Dorn T Grunwald T Chaila E Depondt C Krämer G Delanty N Goldstein DB Sisodiya SM 《Epilepsia》2011,52(8):1388-1392
Purpose: Several recent reports of genomic microdeletions in epilepsy will generate further research; discovery of more microdeletions and other important classes of variants may follow. Detection of such genetic abnormalities in patients being evaluated for surgical treatment might raise concern that a genetic defect, possibly widely expressed in the brain, will affect surgical outcome. Methods: A reevaluation was undertaken of clinical presurgical data, histopathology of surgical specimen, and postsurgical outcome in patients with mesial temporal lobe epilepsy (MTLE) who have had surgical treatment for their drug‐resistant seizures, and who have been found to have particular genomic microdeletions. Key Findings: Three thousand eight hundred twelve patients with epilepsy were genotyped and had a genome‐wide screen to identify copy number variation. Ten patients with MTLE, who had resective epilepsy surgery, were found to have 16p13.11 microdeletions or other microdeletions >1 Mb. On histopathology, eight had classical hippocampal sclerosis (HS), one had nonspecific findings, and one had a hamartoma. Median postsurgical follow‐up time was 48 months (range 10–156 months). All patients with HS were seizure‐free after surgery, International League Against Epilepsy (ILAE) outcome class 1, at last follow‐up; the patient with nonspecific pathology had recurrence of infrequent seizures after 7 years of seizure freedom. The patient with a hamartoma never became seizure‐free. Significance: Large microdeletions can be found in patients with “typical” MTLE. In this small series, patients with MTLE who meet criteria for resective surgery and harbor large microdeletions, at least those we have detected, can have a good postsurgical outcome. Our findings add to the spectrum of causal heterogeneity of MTLE + HS. 相似文献
20.
Striano P Gambardella A Coppola A Di Bonaventura C Bovo G Diani E Boaretto F Egeo G Ciampa C Labate A Testoni S Passarelli D Manna I Sferro C Aguglia U Caranci F Giallonardo AT Striano S Nobile C Michelucci R 《Journal of neurology》2008,255(1):16-23
Introduction
Familial
mesial temporal lobe epilepsy (FMTLE)
is characterized by prominent
psychic and autonomic seizures, often
without hippocampal sclerosis
(HS) or a previous history of
febrile seizures (FS), and good
prognosis. The genetics of this condition
is largely unknown.We present
the electroclinical and genetic
findings of 15 MTLE Italian families.
Patients and methods
FMTLE
was defined when two or more
first-degree relatives had epilepsy
suggesting a mesial temporal lobe
origin. The occurrence of seizures
with auditory auras was considered
an exclusion criterion. Patients underwent
video-EEG recordings, 1.5-Tesla MRI particularly focused on
hippocampal analysis, and neuropsychological
evaluation. Genetic
study included genotyping and
linkage analysis of candidate loci at
4q, 18q, 1q, and 12q as well as
screening for LGI1/Epitempin mutations.
Results
Most of the families
showed an autosomal dominant inheritance
pattern with incomplete
penetrance. Fifty-four (32 F) affected
individuals were investigated.
Twenty-one (38.8 %) individuals
experienced early FS.
Forty-eight individuals fulfilled the
criteria for MTLE. Epigastric/visceral
sensation (72.9 %) was the
most common type of aura, followed
by psychic symptoms
(35.4 %), and déjà vu (31.2 %). HS
occurred in 13.8% of individuals,
three of whom belonged to the
same family. Prognosis of epilepsy
was generally good. Genetic study
failed to show LGI1/Epitempin mutations
or significative linkage to
the investigated loci.
Discussion
FMTLE may be a more common
than expected condition, clinically
and genetically heterogeneous.
Some of the reported families,
grouped on the basis of a specific
aura, may represent an interesting
subgroup on whom to focus future
linkage studies. 相似文献