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1.
Exp Neurol ; 328: 113255, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32084451

RESUMO

We have demonstrated previously that activation of either the ETA or ETB receptor can induce acute electrographic seizures following the intrahippocampal infusion of endothelin-1 (ET-1) in immature (P12) rats. We also demonstrated that activation of the ETA receptor is associated with marked focal ischemia, while activation of the ETB receptor is not. Exploring the mechanisms underlying seizures induced by these two ET-1 receptor interactions can potentially provide insight into how focal ischemia in immature animals produces seizures and whether ischemiarelated seizures differ from seizures not associated with ischemia. To explore these seizure mechanisms we used microdialysis to determine biomarkers associated with seizures in P12 rats following the intrahippocampal infusion of two different agents: (1) ET-1, which activates both the ETA and ETB receptors and causes focal ischemia and (2) Ala-ET-1, which selectively activates only the ETB receptor and does not cause ischemia. Our results show that seizures associated with combined ETA and ETB receptor activation (and ischemia) have a different temporal distribution and microdialysis profile from seizures associated with ETB activation alone (and without ischemia). Seizures with combined activation peak within the first hour after infusion and the microdialysis profile is characterized by a significant increase in the ratio of glutamic acid to GABA. By contrast, seizures with activation of only the ETB receptor peak in the second hour after infusion and microdialysis shows a significant increase in the ratio of leukotriene B4 to prostaglandin E2. These findings suggest that ischemia-related seizures in immature animals involve an imbalance of excitation and inhibition, while non-ischemiarelated seizures involve an inflammatory process resulting from an excess of leukotrienes.


Assuntos
Endotelina-1/toxicidade , Hipocampo/efeitos dos fármacos , Receptor de Endotelina A/metabolismo , Receptor de Endotelina B/metabolismo , Convulsões/metabolismo , Animais , Isquemia Encefálica/induzido quimicamente , Isquemia Encefálica/metabolismo , Hipocampo/metabolismo , Masculino , Ratos , Ratos Wistar , Convulsões/induzido quimicamente
2.
Front Cell Neurosci ; 12: 266, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30210297

RESUMO

Status epilepticus (SE), especially in immature animals, is known to produce recurrent spontaneous seizures and behavioral comorbidities later in life. The cause of these adverse long-term outcomes is unknown, but it has been hypothesized that free radicals produced by SE may play a role. We tested this hypothesis by treating immature (P25) rats with the free radical scavenger N-tert-butyl-α-phenylnitrone (PBN) at the time of lithium chloride (LiCl)/pilocarpine (PILO)-induced SE. Later, long-term outcomes were assessed. Cognitive impairment (spatial memory) was tested in the Morris water maze (MWM). Emotional disturbances were assessed by the capture test (aggressiveness) and elevated plus maze's (EPM) test (anxiety). Next, the presence and severity of spontaneous seizures were assessed by continuous video/EEG monitoring for 5 days. Finally, immunochemistry, stereology and morphology were used to assess the effects of PBN on hippocampal neuropathology and neurogenesis. PBN treatment modified the long-term effects of SE in varying ways, some beneficial and some detrimental. Beneficially, PBN protected against severe anatomical damage in the hippocampus and associated spatial memory impairment. Detrimentally, PBN treated animals had more severe seizures later in life. PBN also made animals more aggressive and more anxious. Correlating with these detrimental long-term outcomes, PBN significantly modified post-natal neurogenesis. Treated animals had significantly increased numbers of mature granule cells (GCs) ectopically located in the dentate hilus (DH). These results raise the possibility that abnormal neurogenesis may significantly contribute to the development of post-SE epilepsy and behavioral comorbidities.

3.
J Thorac Cardiovasc Surg ; 151(4): 1137-42, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26707762

RESUMO

OBJECTIVES: Neonates with congenital heart disease are at risk for impaired neurodevelopment after cardiac surgery. We hypothesized that intraoperative EEG activity may provide insight into future neurodevelopmental outcomes. METHODS: Neonates requiring surgery had continuous intraoperative EEG and hemodynamic monitoring. The level of EEG suppression was classified as either: slow and continuous; moderate burst suppression; severe burst suppression; or isoelectric (no brain activity for >3 minutes). Follow-up neurodevelopmental outcomes were assessed using the Vineland Adaptive Behavior Scale II (Vineland-II). RESULTS: Twenty-one neonates requiring cardiac surgery developed a slow and continuous EEG pattern after general anesthesia. Ten neonates (48%) maintained continuous brain electrical activity with moderate burst suppression as the maximum level of EEG suppression. Eleven neonates (52%) developed severe burst suppression that progressed into an isoelectric state during the deep hypothermic period required for circulatory arrest. However, the duration of this state was significantly longer than circulatory arrest times (111.1 ± 50 vs 22.3 ± 17 minutes; P < .001). At a mean follow-up at 5.6 ± 1.0 years, compared with neonates with continuous brain electrical activity, neonates who developed an isoelectric state had lower Vineland-II scores in communication. There was an inverse relationship between composite Vineland-II scores and duration of isoelectric activity (R = -0.75, P = .01). Of neonates who experienced an isoelectric state, durations of >90 minutes were associated with the lowest Vineland-II scores (125.0 ± 2.6 vs 81.1 ± 12.7; P < .01). CONCLUSIONS: The duration of cortical isoelectric states seems related to neurodevelopmental outcomes. Strategies using continuous EEG monitoring to minimize isoelectric states may be useful during complex congenital heart surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Córtex Cerebral/crescimento & desenvolvimento , Desenvolvimento Infantil , Eletroencefalografia , Cardiopatias Congênitas/cirurgia , Monitorização Neurofisiológica Intraoperatória/métodos , Fatores Etários , Criança , Pré-Escolar , Feminino , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/fisiopatologia , Humanos , Comportamento do Lactente , Recém-Nascido , Masculino , Complicações Pós-Operatórias/fisiopatologia , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
4.
J Clin Neurophysiol ; 32(4): e23-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25839129

RESUMO

PURPOSE: To describe chronological electrographic features of the interictal EEG background observed in two patients with malignant migrating partial epilepsy in infancy from neonatal to early infantile period. METHODS: EEGs of two patients who fulfilled diagnostic criteria for malignant migrating partial epilepsy in infancy were acquired over the period of 6 months to monitor treatment efficacy and characterize seizures and other paroxysmal events. RESULTS: Both patients followed a similar sequential pattern. A distinctive evolution from a dysmature term neonatal EEG pattern to an asynchronous suppression burst pattern was observed before the interictal background becoming continuous. CONCLUSIONS: Physicians providing care to infants with intractable epilepsy and burst suppression EEG pattern should be alert to the possibility of malignant migrating partial epilepsy in infancy. An earlier diagnosis of malignant migrating partial epilepsy in infancy would help to guide diagnostic workup including genetic testing.


Assuntos
Ondas Encefálicas/fisiologia , Encéfalo/fisiopatologia , Eletroencefalografia , Epilepsias Parciais/fisiopatologia , Feminino , Seguimentos , Humanos , Lactente , Masculino
5.
Exp Neurol ; 265: 40-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25542981

RESUMO

The period around birth is a risky time for stroke in infants, which is associated with two major acute and subacute processes: anatomical damage and seizures. It is unclear as to what extent each of these processes independently contributes to poor outcome. Furthermore, it is unclear whether there is an interaction between the two processes - does seizure activity cause additional brain damage beyond that produced by ischemia and/or does brain damage foster seizures? The model of focal cerebral ischemia induced by the intrahippocampal infusion of endothelin-1 (ET-1) in 12-day-old rat was used to examine the role of the endothelin receptors in the development of focal ischemia, symptomatic acute seizures and neurodegeneration. ET-1 (40pmol/µl) was infused either alone or co-administered with selective antagonists of ETA (BQ123; 70nmol/µl) or ETB receptors (BQ788; 70nmol/1µl). Effects of activation of ETB receptors were studied using selective agonist 4-Ala-ET-1 (40pmol/1µl). Regional cerebral blood flow (rCBF) and tissue oxygenation (pO2) were measured in anesthetized animals with a Doppler-flowmeter and a pO2-sensor, respectively. Seizure development was assessed with video-EEG in freely moving rats. Controls received the corresponding volume of the appropriate vehicle (10mM PBS or 0.01% DMSO-PBS solution; pH7.4). The extent of hippocampal lesion was determined using FluoroJade B staining performed 24h after ET-1 infusion. Infusion of ET-1 or ET-1+ETB receptor antagonist reduced rCBF to ~25% and pO2 to ~10% for about 1.5h, whereas selective ETB agonist, ET-1+ETA antagonist and the PBS vehicle had only negligible effect on the rCBF and pO2 levels. Reduction of rCBF was associated with the development of lesion in the injected hippocampus. In all groups, except sham operated and PBS controls, epileptiform activity was observed after activation of the ETA or the ETB receptors. The data revealed a positive correlation between the severity of morphological damage and all the measured seizure parameters (seizure frequency, average and total seizure duration) in the ET-1 group. In addition, the severity of morphological damage positively correlated with the average seizure duration in animals after infusion of ET-1+ETA receptor antagonist or after infusion of ET-1+ETB receptor antagonist. Our results indicate that the activation of ETA receptors is crucial for ischemia development, however either ETA or ETB receptors mediate the development of seizures following the application of ET-1 in immature rats. The dissociation between the ischemic-producing and seizure-producing processes suggests that damage is not necessary to induce seizures, although it may exacerbate them.


Assuntos
Eletroencefalografia , Endotelina-1/administração & dosagem , Hipocampo/metabolismo , Receptor de Endotelina A/metabolismo , Receptor de Endotelina B/metabolismo , Convulsões/metabolismo , Animais , Eletroencefalografia/efeitos dos fármacos , Endotelina-1/toxicidade , Hipocampo/efeitos dos fármacos , Injeções Intraventriculares , Masculino , Ratos , Ratos Wistar , Receptor de Endotelina A/agonistas , Receptor de Endotelina B/agonistas , Convulsões/induzido quimicamente
6.
Pediatr Neurol ; 50(4): 313-7, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24507699

RESUMO

BACKGROUND: During the surgical repair of infants with congenital cardiac defects, there can be periods of decreased cerebral blood flow, particularly during deep hypothermic circulatory arrest. As a result, these infants are at increased risk for seizures and long-term neurodevelopmental difficulties. METHODS: Thirty-two infants with congenital heart disease had continuous video-electroencephalographic (EEG) monitoring pre-, intra-, and postoperatively for 48 hours after surgery. RESULTS: For patients requiring deep hypothermic circulatory arrest (n = 17) the EEG pattern for all patients became suppressed and eventually isoelectric below 25 °C. Two of the 32 infants had electrical seizures within the 48-hour monitoring period. Both required deep hypothermic circulatory arrest, and the burst pattern during recovery had rhythmic, sharp components that were high amplitude and often asynchronous between the hemispheres. The interval between the onset of seizure activity and initiation of the sharp burst pattern during surgery was 29 and 40 hours. This pattern was not observed during isoelectric recovery from infants who did not develop postoperative seizures. CONCLUSIONS: The EEG in infants during deep hypothermic circulatory arrest displayed predictable changes. We identified an electroencephalographic pattern following the isoelectric period that may predict seizure development in the subsequent 48 hours.


Assuntos
Eletroencefalografia/métodos , Cardiopatias Congênitas/cirurgia , Monitorização Neurofisiológica Intraoperatória/métodos , Convulsões/diagnóstico , Convulsões/etiologia , Temperatura Corporal , Encéfalo/fisiopatologia , Feminino , Humanos , Recém-Nascido , Masculino , Período Pós-Operatório , Prognóstico , Convulsões/fisiopatologia , Resultado do Tratamento , Gravação em Vídeo
7.
Ann Vasc Surg ; 16(1): 6-11, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11904797

RESUMO

To determine the reason for differing shunt rates based on electroencephalographic (EEG) and neurologic changes during general and regional anesthetic, respectively, we compared simultaneous EEG tracings and neurologic status in 135 patients undergoing carotid endarterectomy (CEA) under cervical block over a 30-month period. The decision to shunt in these patients was made on the basis of neurologic changes only irrespective of EEG findings. This group was then compared to the 288 patients undergoing CEA under general anesthetic with EEG monitoring over the same period. EEG changes occurred in 7.4% of awake patients and 15.3% of asleep patients (p < 0.03). The rates of ipsilateral hemispheric changes were similar, but no awake patient manifested global EEG changes with clamping while 3.5% of patients under general anesthesia did (p < 0.04). Global, but not hemispheric, changes were correlated with systolic blood pressure variability during clamping. This implies that global EEG changes in anesthetized patients may be the result of the anesthetic technique itself, and that cervical block may in fact be cerebroprotective.


Assuntos
Anestesia Geral/métodos , Eletroencefalografia , Endarterectomia das Carótidas/efeitos adversos , Endarterectomia das Carótidas/métodos , Monitorização Intraoperatória/métodos , Bloqueio Nervoso/métodos , Exame Neurológico , Idoso , Idoso de 80 Anos ou mais , Doenças das Artérias Carótidas/cirurgia , Transtornos da Comunicação/etiologia , Transtornos da Comunicação/cirurgia , Transtornos da Consciência/etiologia , Transtornos da Consciência/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paresia/etiologia , Paresia/cirurgia , Estudos Retrospectivos , Transtornos de Sensação/etiologia , Transtornos de Sensação/cirurgia , Resultado do Tratamento
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