Extract EGb 761 Pretreatment Limits Ubiquitin Positive Aggregates in Rabbit Spinal Cord Neurons after Ischemia-Reperfusion

Abstract

1. Ubiquitin immunohistochemistry was used for investigation of time dependent changes of ubiquitin in the nerve cells reacting to ischemic/reperfusion damage. In the rabbit spinal cord ischemia model a period of 30 min ischemia followed by 24 and 72 h of reperfusion caused neuronal degeneration selectively in the ventral horn motor neurons as well as interneurons of the intermediate zone. 2. Ubiquitin aggregates were accumulated in the neurons of lamina IX and the neurons of intermediate zone destined to die 72 h after 30 min of the spinal cord ischemia. 3. The activation of ubiquitin hydrolytic system is related to a defective homeostasis and could trigger different degenerative processes. Having in mind this, we used EGb 761 to rescue the motor neurons and interneurons against ischemia/reperfusion damage. Our results show that after 30 min of ischemia and 24 or 72 h of reperfusion with EGb 761 pre-treatment for 7 days the vulnerable neurons in the intermediate zone and lamina IX exhibit marked elevation of ubiquitin-positive granules in the cytoplasm, dendrites and nuclei. Abnormal protein aggregates have not been observed in these cells. 4. The rabbits were completely paraplegic after 30 min of ischemia and 24 or 72 h of reperfusion. However, after 7 days EGb 761 pre-treatment, 30 min of ischemia and 24 or 72 h of reperfusion the animals did not show paraplegia. 5. Evaluated ubiquitin-positive neurons of the L(5)-L(6) segments showed significant decrease in number and significant increase of density after 30 min of ischemia followed by 24 h and mainly 72 h of reperfusion. Ubiquitin immunohistochemistry confirmed the protective effect of EGb 761 against ischemia/reperfusion damage in the rabbit spinal cord.

Effect of Noradrenalin and EGb 761 Pretreatment on the Ischemia-Reperfusion Injured Spinal Cord Neurons in Rabbits

“…In our previous study, we have demonstrated localization of protein ubiquitin, by ubiquitin immunohistochemistry, in the spinal cord neurons of rabbits pretreated with EGb 761 before 30 min of ischemia followed by 48 or 72 h of reperfusion (Mechírová et al 2006). In this present study, we completed ubiquitin distribution in the spinal cord neurons after noradrenalin preconditioning.…”

“…Ubiquitin aggregates have never been visible. Ubiquitin aggregates are the signs of damaged, degenerated cells that have lost the ability of intracellular hydrolytic degradation of altered proteins (Mechírová et al 2006). In this study, we extended our previous results with the ubiquitin immunohistochemistry in the groups of animals with noradrenalin preconditioning, and also decided to use Fluoro Jade B fluorescent method for quantitative analysis of degenerated neurons in all our experimental groups.…”

“…Neurons, unable to synthesize new ubiquitin, appear to be those that succumb to the degenerative process induced by ischemia. In our previous study, we reported that a period of 30 min ischemia followed by 24 and 72 h of reperfusion caused neuronal degeneration selectively in the spinal cord ventral horn motor neurons as well as interneurons of the intermediate zone in rabbits (Mechírová et al 2006). Ubiquitin aggregates were accumulated in the cytoplasm of neurons in laminae VIII and IX destined to die 72 h after 30 min of spinal cord ischemia.…”

Effects of Ginkgo biloba Extract on Spinal Cord Ischemia–Reperfusion Injury in Rats

“…2 The dosage and administration intervals of EGb in our study were similar to previous studies in the literature. In a study by Mechirova et al, 21 30 min of infrarenal aortic ischemia resulted in paraplegia in all test animals and 40 mg/kg of EGb for 7 days resulted in significant recovery from paraplegia. The study showed that the EGb had a protective effect against IR injury in the spinal cord.…”

Effect of Antioxidant Treatment in Global Ischemia and Ischemic Postconditioning in the Rat Hippocampus

“…Bilobalide component of EGb 761 increases the respiratory control ratio of mitochondria and protects against the uncoupling of oxidative phosphorylation, by this way increases ATP levels (DeFeudis 2002), influences cognitive deficits that follow stress or traumatic brain injury (DeFeudis and Drieu 2000). Positive effects of EGb 761 pretreatment on neurons after ischemia/reperfusion were confirmed by studies of global ischemia in the rats (Hrehorovska et al 2004;Domorakova et al 2006) or in the gerbils (Chandrasekaran et al 2002) and in the rabbit spinal cord ischemia (Mechirova and Domorakova 2002;Mechirova et al 2006). Less data were found about ischemia/reperfusion and EGb 761 posttreatment.…”