Time course of acute neuroprotective effects of lidocaine evaluated by brain impedanciometry in the global ischemia model.

Voltage-activated sodium channels play a primary role during ischemic brain edema and thus are a pharmacological target for therapy. Lidocaine, a sodium channel blocker, was tested in male Sprague-Dawley rats anesthetized with thiobarbital (60 mg·kg(-1) i.p.) and perfused i.v. with Ringer's solution (n = 9) or lidocaine (0.75 mg·kg(-1), n = 9, or 1.5 mg·kg(-1), n = 6). Two tungsten microelectrodes were implanted in the cerebral cortex to register changes in tissue impedance in response to the voltage fall of a square wave electric pulse (100 µA, 10 ms), before and after infusion of lidocaine or Ringer's solution and during global cerebral ischemia due to a respiratory arrest induced by D-tubocurarine. Lidocaine infusion under normoxic conditions did not change voltage values (Mann-Whitney U = 51; p > 0.05). In animals infused with Ringer's solution, the voltage fall induced by global cerebral ischemia was fast for ∼8 min at -8.0 ± 2.3%·min(-1) followed by a slow decay at -0.96 ± 0.17%·min(-1). The time constant of voltage decay (λ) was 215.6 s (F = 547.4; p = 0.00000). Voltage values of lidocaine-infused animals were significantly higher than those of rats infused with Ringer's solution (U = 100; p = 0.000089). The decay rates were -4.97 ± 1.36%·min(-1) (fast phase) and -1.04 ± 0.3%·min(-1) (slow phase) with λ = 672.5 s (+211.9%; p = 0.000000). These results suggest that lidocaine significantly reduced cerebral impedance, hence exerting a strong early anti-edema effect probably by blocking voltage-activated sodium channels.

Time course of acute neuroprotective effects of lithium carbonate evaluated by brain impedanciometry in the global ischemia model.

It is well known that chronic treatment with lithium gives cytoprotection from ischemia and neurodegeneration. Despite the clinical relevance, the potential effects of acute lithium treatment just before and during early stages of ischemia are not well known. Brain impedance was measured in an experimental global ischemia model, to determine these potential effects and their time course,as measured in minutes. Thiobarbital anesthetized (60 mg·kg(-1), intraperitoneal injection) male Sprague-Dawley rats were infused intravenously (i.v.) with isovolumetric amounts of ringer (n = 10 rats) or lithium (Li(2)CO(3); 10; 30; 100 mg·kg(-1); n = 6 rats per dose tested). Cortico-subcortical impedance was recorded before (20 min) and after (20 min) the infusion, and during global cerebral ischemia (20 min) induced by cardiopulmonary arrest due to the administration of D-tubocurarine. Lithium did not change tissue impedance in normoxid animals. In the ringer-infused group, global cerebral ischemia first (9 min) shows a fast voltage decay rate (-7.08%·min(-1)), followed by a slow one (-0.94%·min(-1)) for the last 11 min of the recording. Lithium, at any dose tested, induced a strong reduction in voltage decay for both fast (-3.7%·min(-1)) and slow (-5.2%·min(-1)) phases, although the reduction was more intense in the first phase (>58%, Mann-Whitney Z = 2.02; P < 0.043). The reduction was more effective at 10 mg (Li2CO3)·kg(-1) than at 30 or 100 mg·kg(-1). The time course of brain edema was defined by curve fitting for ringer- (time constant λ = 512.9 s) or lithium-infused animals (λ = 302.0 s). These results suggest that acute lithium infusion 20 min prior to global ischemia, strongly reduces cerebral impedance by reducing the decay rate and the duration of the fast decay phase, and increasing time constant decay during ischemia.

Cambios en la perfusión cerebral inducidos por etomidato en pacientes con epilepsia del lóbulo temporal / Changes in cerebral perfusión induced by etomidate in patients with temporal lobe epilepsy

Resumen. Introducción. La epilepsia es uno de los mayores trastornos neurológicos. Afecta a alrededor del 0,5-2% de la población mundial, y entre el 20-25% de los pacientes son resistentes a la medicación. Objetivo. Analizar la respuesta de la perfusión cerebral –valorada mediante tomografía simple por emisión de fotón único (SPECT)– y la actividad bioeléctrica –en scalp y región temporal mesial– a la aplicación de etomidato. Pacientes y métodos. Se estudiaron 10 pacientes evaluados prequirúrgicamente y estudiados mediante videoelectroencefalograma (video-EEG) con electrodos de foramen oval (EFO) y SPECT. Se administró etomidato (0,1 mg/kg de peso), seguido por 99mTc-HmPAO, durante el estudio en el video-EEG + EFO. Resultados. Los efectos secundarios consistieron en mioclonías (n = 7) y dolor moderado (n = 2). No se han observado efectos cardiovasculares o respiratorios significativos. La actividad bioeléctrica en scalp consistió en una actividad rápida inicial breve, seguida por un patrón delta generalizado e hipervoltado durante varios minutos. En la región irritativa, se observó un marcado incremento de la actividad interictal. La perfusión cerebral aumentó, en general en todas las áreas estudiadas, especialmente en la región temporal (lateral y mesial) y en las áreas talámicas. En la cola del hipocampo no epileptógeno, se ha observado el segundo mayor incremento en la perfusión cerebral, y es la única región que se diferencia de la contralateral. Conclusiones. La activación mediante etomidato da lugar a una respuesta específica y repetible sobre la actividad bioeléctrica. Además, la perfusión cerebral local muestra cambios relacionados directamente con la región epileptógena, y puede servir, por tanto, como herramienta diagnóstica en un futuro inmediato (AU)

Summary. Introduction. Epilepsy is one of the major neurological disorders, affecting roughly 0.5-2% of the world’s population and approximately 20-25% of patients are resistant to medication. Aim. To analyze the response of cerebral perfusion (assessed by SPECT) and bioelectrical activity (measured in scalp and mesial temporal region) to etomidate. Patients and methods. We studied 10 patients presurgically evaluated and studied by video-EEG with foramen ovale electrodes (EFO) and SPECT. Etomidate was administered (0.1 mg/kg), followed by 99mTc-HmPAO during the study in the video-EEG + EFO. Results. The side-effects consisted of myoclonus (n = 7) and moderate pain (n = 2). There had been no significant respiratory or cardiovascular effects. The bioelectrical activity in the scalp consisted in a brief initial rapid activity, followed by a generalized and hypervoltaged delta pattern for several minutes. In the epileptogenic zone, there was a marked increase of interictal activity. Increased cerebral perfusion was observed in all areas studied, especially in temporal region (mesial and lateral) areas and thalamus. In the tail of the non-epileptic hippocampus, we observed the second largest increase in cerebral perfusion, the only region that is different from contralateral area. Conclusions. Activation by etomidate induces a specific and repetitive response in the bioelectrical activity. In addition, cerebral perfusion changes directly related to the epileptogenic region may serve therefore as a diagnostic tool in the near future (AU)

[Changes in cerebral perfusion induced by etomidate in patients with temporal lobe epilepsy]. / Cambios en la perfusión cerebral inducidos por etomidato en pacientes con epilepsia del lóbulo temporal.

INTRODUCTION: Epilepsy is one of the major neurological disorders, affecting roughly 0.5-2% of the world's population and approximately 20-25% of patients are resistant to medication. AIM: To analyze the response of cerebral perfusion (assessed by SPECT) and bioelectrical activity (measured in scalp and mesial temporal region) to etomidate. PATIENTS AND METHODS: We studied 10 patients presurgically evaluated and studied by video-EEG with foramen ovale electrodes (EFO) and SPECT. Etomidate was administered (0.1 mg/kg), followed by (99)mTc-HmPAO during the study in the video-EEG + EFO. RESULTS: The side-effects consisted of myoclonus (n = 7) and moderate pain (n = 2). There had been no significant respiratory or cardiovascular effects. The bioelectrical activity in the scalp consisted in a brief initial rapid activity, followed by a generalized and hypervoltaged delta pattern for several minutes. In the epileptogenic zone, there was a marked increase of interictal activity. Increased cerebral perfusion was observed in all areas studied, especially in temporal region (mesial and lateral) areas and thalamus. In the tail of the non-epileptic hippocampus, we observed the second largest increase in cerebral perfusion, the only region that is different from contralateral area. CONCLUSIONS: Activation by etomidate induces a specific and repetitive response in the bioelectrical activity. In addition, cerebral perfusion changes directly related to the epileptogenic region may serve therefore as a diagnostic tool in the near future.

[Role of astrocytes activated by albumin in epileptogenesis]. / Participación de los astrocitos activados mediante albúmina en la epileptogénesis.

INTRODUCTION: Epilepsy is one of the major neurological disorders characterized by spontaneous and recurrent seizures. Despite progress in the understanding of epilepsy, the exact network underlying the seizures is unclear. DEVELOPMENT: Actually the role of astrocytes in modulation of neuronal activity and the synaptic transmission is clear, making astrocytes as important players in processing of information in the central nervous system. These characteristics make us think that astrocytes have an important role in the epileptogenesis. Disruption of blood brain-barrier let the pass of albumin, and it could uptake into astrocytes. Numerous authors suggest that this can contribute to epileptogenesis. CONCLUSION: In view the data obtained from these factors (astrocytes and albumin), future studies will undoubted further to know its relation with epileptogenesis in humans and as therapeutics aims.

Participación de los astrocitos activados mediante albúmina en la epileptogénesis / Role of astrocytes activated by albumin in epileptogenesis

Introducción. La epilepsia es uno de los mayores trastornos neurológicos, afectando a cerca del 0,5-2% de la población mundial. Se caracteriza por la aparición de crisis espontáneas de forma recurrente. A pesar de los avances en el entendimiento de la epilepsia, las bases celulares exactas por las que ocurre la epilepsia humana no están claras. Desarrollo. Actualmente, el papel de los astrocitos en la modulación de la actividad neuronal y la transmisión sináptica está consolidado,ya que estas células se han convertido en unos actores importantes en el manejo de la información en el sistema nervioso. Estas características pueden hacen pensar en los astrocitos como elementos que poseen un papel importante, cuanto menos, en la epileptogénesis. Numerosos autores relacionan la rotura de la barrera hematoencefálica con la epilepsia, lo que origina laentrada masiva de albúmina al cerebro, donde ésta sería captada por los astrocitos, convirtiéndose en un factor importante en la alteración de su actividad y desencadenando cambios en ellos que conducirían a la epileptogénesis. Conclusión. A la vista de los datos observados para estos dos factores (astrocitos y albúmina), sin duda debería plantearse la realización de estudios para conocer en profundidad su implicación en la epileptogénesis y su posible uso como dianas terapéuticas

Introduction. Epilepsy is one of the major neurological disorders characterized by spontaneous and recurrentseizures. Despite progress in the understanding of epilepsy, the exact network underlying the seizures is unclear. Development. Actually the role of astrocytes in modulation of neuronal activity and the synaptic transmission is clear, making astrocytes asimportant players in processing of information in the central nervous system. These characteristics make us think that astrocytes have an important role in the epileptogenesis. Disruption of blood brain-barrier let the pass of albumin, and it could uptake into astrocytes. Numerous authors suggest that this can contribute to epileptogenesis. Conclusion. In view thedata obtained from these factors (astrocytes and albumin), future studies will undoubted further to know its relation with epileptogenesis in humans and as therapeutics aims

[The effectiveness and tolerance of piribedil as adjunct therapy to levodopa in patients with Parkinson's disease: a nine month follow up]. / Eficacia y tolerancia del piribedil como terapia adjunta a la levodopa en pacientes con enfermedad de Parkinson: seguimiento de nueve meses.

INTRODUCTION: Piribedil is a D2 D3 dopamine agonist, which has been shown to be well tolerated and to improve Parkinsonian symptoms, particularly tremor. However, few studies have been published about this Dopamine Agonist as an adjunct to levodopa therapy in patients with Parkinson's disease (PD). This placebo controlled, parallel group study was undertaken to investigate the effects of piribedil in PD patients insufficiently controlled with levodopa in a nine months follow up. PATIENTS AND METHODS: We included 62 PD patients insufficiently controlled with levodopa and needed an increase in dopamine stimulation. Patients were randomized in two similar groups, one of them taking Piribedil and levodopa and the other group taking a placebo and levodopa. The primary efficacy measures were the items II and III of the UPDRS. The patients were evaluated prior to the start of therapy, and 3, 6 and 9 months after the start of the study. RESULTS: Patients taking Piribedil showed an average of improvement of 37,8% (p < 0.01) in the part II and 63,2% (p < 0.01) in the part III of the UPDRS at the end of the study. At 9 month evaluation, tremor at rest showed an average improvement of 68,6%, rigidity, fingers taps and legs agility improved substantially in their respective items of the UPDRS at the end of the study. CONCLUSIONS: We concluded that PD patients with functional worsening while on stable levodopa doses exhibit a steady improvement of the UPDRS part II and III with the adjunction of Piribedil 150 mg mean daily dose for 9 months.

Eficacia y tolerancia del piribedil como terapia adjunta a la levodopa en pacientes con enfermedad de Parkinson: seguimiento de nueve meses / The effectiveness and tolerance of piribedil as adjunct therapy to levodopa in patients with Parkinson's disease: a nine-month follow-up

Introducción. El piribedil es un agonista dopaminérgico (AD) D2-D3, eficaz en el control de síntomas parkinsonianos, particularmente el temblor. Sin embargo, hay pocos estudios publicados con seguimientos mayores de tres meses sobre este AD como terapia adjunta a la levodopa en pacientes con la enfermedad de Parkinson (EP). Este estudio se diseñó para investigar los efectos del piribedil en pacientes con EP, tratados con levodopa y con deterioro funcional (DF) en un seguimiento de nueve meses. Pacientes y métodos. Incluimos 62 pacientes con EP sin complicaciones atribuibles a la levodopa y con DF y motor. Los pacientes se distribuyeron de una manera aleatoria en dos grupos similares, levodopa más piribedil o levodopa más placebo. La eficacia se valoró con las partes II y III de la escala unificada para la valoración de la EP (UPDRS) y la tolerancia se valoró con un cuestionario para detectar efectos adversos. Se hizo una valoración basal y a los 3, 6 y 9 meses posteriores al inicio de la terapia. Resultados. Los pacientes que tomaron piribedil mostraron un porcentaje diferencial de mejoría de 37,8 por ciento (p < 0,01) en la parte II del UPDRS y 63,2 por ciento (p < 0,01) en la parte III del UPDRS. Mostraron una mejoría del 68,6 por ciento en el ítem `temblor de reposo' al final del protocolo; también hubo una mejoría notable en el resto de los síntomas cardinales parkinsonianos. Conclusión. Los pacientes de este estudio, con EP y DF, mostraron una mejoría progresiva y sostenible en las partes II y III de la UPDRS durante nueve meses al agregarse 150 mg/día de piribedil, como terapia adjunta a la levodopa. Los efectos adversos fueron similares a los comunicados por otros AD (AU)

Introduction. Piribedil is a D2-D3 dopamine agonist, which has been shown to be well tolerated and to improve Parkinsonian symptoms, particularly tremor. However, few studies have been published about this dopamine agonist as an adjunct to levodopa therapy in patients with Parkinson’s disease (PD). This placebo controlled, parallel group study was undertaken to investigate the effects of piribedil in PD patients insufficiently controlled with levodopa in a nine months follow up. Patients and methods. We included 62 PD patients insufficiently controlled with levodopa and needed an increase in dopamine stimulation. Patients were randomized in two similar groups, one of them taking piribedil and levodopa and the other group taking a placebo and levodopa. The primary efficacy measures were the items II and III of the UPDRS. The patients were evaluated prior to the start of therapy, and 3, 6 and 9 months after the start of the study. Results. Patients taking piribedil showed an average of improvement of 37,8% (p < 0.01) in the part II and 63,2% (p < 0.01) in the part III of the UPDRS at the end of the study. At 9-month evaluation, tremor at rest showed an average improvement of 68,6%, rigidity, fingers taps and legs agility improved substantially in their respective items of the UPDRS at the end of the study. Conclusions. We concluded that PD patients with functional worsening while on stable levodopa doses exhibit a steady improvement of the UPDRS part II and III with the adjunction of piribedil 150 mg mean daily dose for 9 months (AU)