Glutathione depletion: Starting point of brain metabolic stress, neuroinflammation and cognitive impairment in rats.

Glutathione provides protection from oxidative stress-induced damage through the reduction of reactive oxygen species for the maintenance of oxidant homeostasis. Our purpose was to test the effects of depleting tissue GSH by buthionine sulfoximine on brain oxidative metabolism and cognitive performance in rats. Glutathione depletion induced a compensatory response on antioxidant enzymes and increase of cell damage indicators in all the examined cerebral areas at 24h. The effect of GSH depletion on spatial memory recorded at 24h post-surgery showed significant differences between experimental groups for the escape latency to the platform and percentage of total swim distance spending in the target quadrant. The acquisition of a new spatial condition 24h after GSH depletion revealed differences between experimental groups for latencies, swim distance, swim distance in the target quadrant and percentage of total swim distance spending in the target quadrant. The ability of BSO treated group to maintain a restraining behavior was significantly smaller compared with control group. We founded significant correlation among variables of the behavioral studies and oxidative stress indicators. In conclusion, our model shows how increased ROS production by transitory glutathione depletion constitutes the primary cause to neuronal metabolic stress with alterations in synaptic signaling and cognitive deficits.

Modelo experimettal de hipoperfusión cerebral poduce déficit de la memoria y aaprendizaje y modificaciones en la expresión de genes / Experimental Model of Cerebral Hypoperfusion Produced Memory-learning Deficits, and Modifications in Gene Expression

A escala mundial, la isquemia cerebral constituye una de las principales causas de muerte, por lo que los modelos animales de isquemia cerebral son extensamente usados tanto en el estudio de la pato-fisiología del fenómeno isquémico; como en la evaluación de agentes terapéuticos con posible efecto protector o regenerador. Los objetivos de este estudio fueron examinar la presencia de daño neuronal en diferentes áreas cerebrales como consecuencia del evento isquémico; así como evaluar consecuencias de este proceder sobre los procesos de memoria-aprendizaje. Los grupos de estudios incluyeron un grupo experimental de animales isquémicos, 30 ratas a las que se les ocluyó ambas arterias carótidas comunes, y un grupo control. Fue evaluada la expresión de genes isquémicos e inflamatorios por técnicas de qPCR 24 horas post lesión, la morfología del tejido cerebral en áreas de corteza, estriado e hipocampo, siete días post lesión y los procesos de memoria y aprendizaje, 12 días post lesión. Los estudios morfológicos evidenciaron que el proceder induce la muerte de poblaciones celulares en corteza, estriado e hipocampo; la isquemia modificó la expresión los genes gfap, ho-1, il-6, il-17 e ifn-γ, lo cual puede ser utilizado como un marcador de proceso isquémico temprano. Adicionalmente, el daño isquémico causó un deterioro en la memoria espacial. Esta caracterización nos permite contar con un modelo experimental donde desarrollar futuros estudios sobre la patofisiología de los eventos isquémicos y la evaluación de estrategias terapéuticas.

Cerebral ischemia is a major cause of death, for this reason animal models of cerebral ischemia are widely used to study both the pathophysiology of ischemic phenomenon and the evaluation of possible therapeutic agents with protective or regenerative properties. The objectives of this study were to examine the presence of neuronal damage in different brain areas following the ischemic event, and assess consequences of such activities on the processes of memory and learning. The study group included an experimental group ischemic animals (30 rats with permanent bilateral occlusion of the carotids), and a control group. Was evaluated gene expression and inflammatory ischemic by qPCR techniques 24h post injury, brain tissue morphology in areas of cortex, striatum and hippocampus seven days post injury and processes of memory and learning, 12 days post injury. The morphological studies showed that the procedure induces death of cell populations in cortex, striatum and hippocampus, ischemia modified gfap gene expression and ho, il-6, il-17 and ifn-γ, which can be used as a marker of early ischemic process. Additionally, the ischemic injury caused spatial memory decline. This characterization gives us an experimental model to develop future studies on the pathophysiology of ischemic events and assessing therapeutic strategies.

Hippocampal neurotrophins after stimulation of the basolateral amygdala, and memory improvement in lesioned rats.

PURPOSE: To investigate a possible role of neurotrophins in the memory improving effect of stimulating the basolateral amygdala. METHODS: The BDNF and NGF levels were measured in the hippocampus of fimbria-fornix lesioned male rats after four days of training in the water maze and stimulation of the basolateral amygdala. RESULTS: The behavioral results confirm that daily post-training stimulation of the amygdala improves the learning abilities of the lesioned animals. BDNF increased in lesioned and trained animals, but stimulating the basolateral amygdala induces a significantly greater increase. NGF showed a slight (but significant) increase in fimbria-fornix lesioned and trained animals, but stimulating the amygdala does not produce a further increase. In separate groups of animals we measured the levels of both neurotrophins in acute experiments, after 2 and 24 hours of stimulating the amygdala. BDNF was significantly increased at both times, while NGF showed again only slight increases (significant at 24 h). CONCLUSIONS: These results suggest that the BDNF response to amygdala stimulation might be of functional importance in the observed learning improvement. The changes in NGF are most likely due to the accumulation of this protein after removal of the septal axons.

Evolución de la memoria episódica en pacientes epilépticos sometidos a lobectomía temporal / Evolution of episodic memory in epileptic patients submitted to temporal lobectomy

Introducción: La memoria episódica resulta vulnerable a la lobectomía temporal. Nuestro objetivo es describir los cambios que aparecen en este subsistema de memoria, en pacientes sometidos a lobectomía temporal realizada como estrategia para control de crisis. Pacientes y Métodos: La muestra está compuesta por 11 pacientes, los cuales fueron evaluados antes de realizar la lobectomía temporal y al año de ésta, utilizando una batería de pruebas neuropsicológicas. Resultados: Observamos disminución en el rendimiento mnésico, en la modalidad ipsilateral al hemisferio donde se realiza la lobectomía y aumento en la modalidad relacionada con el hemisferio contralateral a la intervención. Sin embargo estas diferencias en elrendimiento entre los dos momentos evaluativos no se manifiestan en igual magnitud en todas las variables evaluadas ni alcanzan valor estadístico significativo. Conclusiones: Asociado a la lobectomía temporal el perfil neuropsicológico de la memoria episódica muestra disminución del rendimiento en la modalidad ipsilateral a la cirugía y mejoría en la modalidad contralateral, evolución esta que refuerza el supuesto de lateralización funcional.

Introduction: Episodic memory is vulnerable to temporal lobectomy. Our objective is to describe the changes that appear in this memory sub-system in patients submitted to temporal lobectomy, as a strategy to crisis control. Patients and methods: The simple is composed of 11 patients who were evaluated before performing the temporal lobectomy and a year after, using neuropsychologic tests.Results: We observed a diminishing in the mnesic rendering, in the ipsilateral modality to the hemisphere where the lobectomy is performed and an increase in the modality related with the contralateral hemisphere to that of the intervention. But nevertheless, these differences as to the rendering of the evaluative moments that neither manifest themselves in thesame magnitude in all evaluated variables nor reach significant statistical value. Conclusions: The neuropsychologic profile of episodic memory associated to temporal lobectomy shows a diminishing in therendering of ipsilateral modality to surgery, but an improvement in the contralateral modality an evolution that reinforces the supposing of a functional lateralization.

A neurofunctional evaluation strategy for presurgical selection of temporal lobe epilepsy patients.

Introduction Temporal lobe epilepsy (TLE) is the prototype of a surgically correctable syndrome. Successful surgical outcomes depend on a thorough presurgical evaluation aimed primarily at identifying the epileptogenic zone. Objective Describe the noninvasive presurgical selection and evaluation strategy for TLE patients introduced at the International Neurological Restoration Center (CIREN) in Havana, Cuba, and evaluated between 2001 and 2006 for its accuracy in identifying candidates for non-lesional resection surgery. Methods Ictal onset electrographic patterns of 1,679 seizures in 72 patients with drug-resistant partial epilepsy, obtained through longterm scalp Video EEG (V-EEG) monitoring, were evaluated. The correlation between the V-EEG-defined epileptogenic zone and the dysfunction shown by single photon emission computed tomography (ictal and interictal brain SPECT) and nuclear magnetic resonance spectroscopy (MRS) was established. Results V-EEG monitoring determined that 44.4% of evaluated patients had complex partial temporal lobe seizures. Identification of patients with medial temporal epilepsy (MTE) increased as a result of lateralization and localization of the dominant mean ictal pattern frequency (5.56 ± 1.31 Hz) during the period of maximum spectral power VARETA localization of an ictal epileptiform activity source coincided with the epileptogenic zone in all TLE patients who subsequently underwent a successful temporal lobectomy. Semiquantitative analysis of ictal and interictal brain SPECT images, as well as metabolic ratios measured by MRS, combined with V-EEG findings, enabled localization/lateralization of the epileptogenic zone in TLE patients whose MRIs were normal or showed bilateral structural abnormalities. Conclusions Confirmation of correct localization/lateralization of the epileptogenic zone following successful surgical outcomes in selected TLE patients led CIREN to develop a surgical treatment strategy for patients in Cuba with drug-resistant temporal lobe epilepsy. This strategy offers an appropriate, cost-effective treatment alternative for developing countries like Cuba, with the benefit of significantly improving TLE patients' quality of life.

Oxidative stress markers in surgically treated patients with refractory epilepsy.

OBJECTIVES: This study examines the redox status of drug-resistant epileptic patients and how it is modified after surgical treatment. DESIGN AND METHODS: The activity of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase), and markers of damage to biomolecules (malondialdehyde and advanced oxidation protein products) were determined by spectrophotometric methods in the serum of 9 drug-resistant epileptic patients, before and at different times after surgery, and in 32 control subjects. RESULTS: Pre-surgery, epileptic patients presented increases in markers of oxidative damage and alterations in the activities of antioxidant enzymes. Additionally, patients showed a correlation between advanced oxidation protein products and the evolution time of the illness. After surgery, patients showed a trend to normalization in all the measured variables, except for the superoxide dismutase activity. CONCLUSIONS: Drug-resistant temporal lobe epilepsy is associated with an oxidative stress condition that is favourably modified by the surgical resection of the epileptic foci.