Postconditioning and Anticonditioning: Possibilities to Interfere to Evoked Apoptosis

Abstract

The aim of this study was to validate the ability of postconditioning, used 2 days after kainate intoxication, to protect selectively vulnerable hippocampal CA1 neurons against delayed neuronal death. Kainic acid (8 mg/kg, i.p.) was used to induce neurodegeneration of pyramidal CA1 neurons in rat hippocampus. Fluoro Jade B, the specific marker of neurodegeneration, and NeuN, a specific neuronal marker were used for visualization of changes 7 days after intoxication without and with delayed postconditioning (norepinephrine, 3.1 mumol/kg i.p., 2 days after kainate administration) and anticonditioning (Extract of Ginkgo biloba, 40 mg/kg p.o used simultaneously with kainate). Morris water maze was used on 6th and 7th day after kainate to test learning and memory capabilities of animals. Our results confirm that postconditioning if used at right time and with optimal intensity is able to prevent delayed neuronal death initiated not only by ischemia but kainate intoxication, too. The protective effect of repeated stress-postconditioning was suppressed if extract of Ginkgo biloba (EGb 761, 40 mg/kg p.o.) has been administered together with kainic acid. It seems that combination of lethal stress and antioxidant treatment blocks the activation of endogenous protecting mechanism known as ischemic tolerance, aggravates neurodegeneration and, after repeated stress is able to cause cumulative damage. This observation could be very valuable in situation when the aim of treatment is elimination of unwanted cell population from the organism.

Neuroprotective Effects of IGF-I Following Kainic Acid-Induced Hippocampal Degeneration in the Rat

“…Furthermore, it has been proposed that this strongly basic molecule expressed by the degenerating neurons, to which the FluoroJade B stain binds, is involved in the degeneration process itself (Schmued et al 1997). In agreement with our results, Burda et al (2009) have shown FluoroJade B-positive cells in areas of the degenerating hippocampus devoid of neurons. When IGF-I was administered together with KA, the number of degenerating neurons, as detected by FluoroJade B staining was significantly decreased.…”

Oxygen Glucose Deprivation in Rat Hippocampal Slice Cultures Results in Alterations in Carnitine Homeostasis and Mitochondrial Dysfunction

“…Although our data do not allow us to delineate the mechanism by which this pre-conditioning is occurring, it may be mediated by an LCAR-dependent increase in anti-oxidant enzyme capacity. Studies have demonstrated that mild ischemia can upregulate SOD1, SOD2 and catalase in hippocampal tissue [29], [30]. Blocking this effect with an antisense to SOD1 significantly decreases the neuroprotective effect [31], [32], [33].…”

The End Effector of Ischemic Tolerance Present in Blood Plasma from Double Conditioned Donors Ameliorates Trimethyltin Provoked Damage in Brain

“…The therapeutic window differs for different kinds of tissues or cells and depends on the type of stress, its intensity, and the length of exposure as well as the temperature of the affected tissue. The delayed neuronal death occurring after global cerebral ischemia as well as some apoptosis-inducing intoxications offer two-day wide therapeutic window and enables to effectively use delayed postconditioning even 48 h after pathology [1,7,8]. These studies indicated that for the acquisition of full tolerance, a combination of two stresses is necessary.…”