Effect of central microinjection of carbenoxolone in an experimental model of focal cerebral ischemia

Previous experimental studies have shown the protective effects of CBX on brain ischemic injures in global and in vitro models of ischemia. However, effects of CBX in temporary model of focal cerebral ischemia are not clear. Hence, the aim of this study was to investigate the effects of central micro injection of CBX on post-ischemic reperfusion injuries in a temporary model of focal cerebral ischemia. Transient focal cerebral ischemia was induced in rats by 60 min middle cerebral artery occlusion [MCAO], followed by 23 h reperfusion. CBX was administered into the right ventricle at doses of 1, 12, 25, 50 and/or 100 micro g/kg at the beginning of MCAO. Cortical and striatal infarct volumes and motor dysfunctions were assessed 24 h after MCAO. Administration of CBX at doses of 1, 12, 25 and/or 50 micro g/kg significantly reduced cortical infarct volumes by 35%, 49%, 41% and 43%, respectively [P<0.001]. In addition, CBX only at dose of 25 micro g/kg significantly reduced striatal infract volume and improved neurological dysfunctions [P<0.01]. Our findings indicated that central microinjection of CBX has protective effect on against ischemic reperfusion injuries in a transient model of focal cerebral ischemia

Memory deficits after recovery of transient forebrain ischemia in rats: a preliminary report

Transient forebrain ischemia causes delayed cell death of vulnerable neuronal populations, in rodents, primates and man, mainly in the pyramidal CA1 sector of the hippocampus. Lesions involving hippocampal formation are of great interest due to its recognized importance in information processing. In a series of experiments, we investigated the performance of rats after recovery of an ischemic episode, in two avoidance tasks and in one appetitive task with a spatial component. Wistar rats were subjected to transient forebrain ischemia (ISC) through electrocauterization of vertebral arteries and 20 min occlusion of common carotids. One group was tested 21 to 28 days after ISC, and another 7 months after the episode, along with agematched controls. Ischemic animals tested in the early phase of recovery showed impairment of both inhibitory and active avoidance tasks, as well as the water-finding task. However, ischemic rats tested after long-term recovery exhibited avoidance deficits in the active, but not in the inhibitory task, and presented higher latencies of water-finding. Considering that the pattern of cognitive impairment after short and long recovery periods is different, we suggest that neuronal circuitry involved in the tasks studied may be influenced by the probable reorganization of hippocampal synapses after recovery from an ischemic episode.

Antagonistas del receptor NMDA en isquemia cerebral focal: modelo experimental / Antagonist of NMDA receptors on focal cerebral ischemia:experimental model

En el daño neuronal isquémico, uno de los mecanismos finales de la lesión celular es la entrada abrupta de calcio al interior de la célula mediada por canales depredientes de voltaje o por activación de receptores NMDA (N-metil D-aspartato), que origina destrucción de las membranas y el citoesqueleto. Se probó la utilidad terapeútica de un bloqueador no competitivo del receptor NMDA (MK-801, 2mg/kg intraperitoneal), para reducir la extensión del daño neuronal en un modelo de oclusión de la arteria cerebral media en rata. El MK-801 se administró 10 minutos antes (grupo 3) y una hora después de la oclusión (grupo 4), y los resultados se compararon con un grupo de oclusión sin medicamento (grupo 2) y un grupo control (grupo 1). Se encontró que la administración de MK-801 redujo significativamente el área de infarto en relación al grupo de oclusión sin medicamento (p < 0.05), con mayor efectividad cuando se administró de forma profiláctica (10 minutos antes de la oclusión) (grupo 3). Estos resultados sugieren que el MK-801 puede ser efectivo en la prevención de daño neurológico post-isquémico. Sin embargo, antes de recomendar su aplicación clínica, deberán definirse sus posibles efectos colaterales