Brain Poster Session: Neuroprotection

Abstract

Objectives: In the central nervous system, recombinant human erythropoietin (rhEPO) attenuates ischemic injury in vitro and in vivo. However, megadose of rhEPO is required to attain the protective effect, and that is afraid of accumulating thrombus and aggravating brain damage by upregulating the red blood cell count and hyperactive platelet. The nonerythropoietic asialoerythropoietin (asia-loEPO),which is generated by total enzymatic desialylation of rhEPO, has extremely short plasma half life and has possibility of neuroprotective effect to the brain ischemia. In this study, we showed that asialoEPO protects neurons against delayed neuronal death in the hippocampal pyramidal cells after transient forebrain ischemia. Methods: 23 adult gerbils received 3 mins bilateral common carotid artery occlusion. The drug (asialoEPO 10 U/g, rhEPO 10 U/g) or vehicle was injected intraperitoneally three times, 3 h before, just after, and 24 h after the insult. Animals were allowed to survive for 7 days. Learning ability test and retention test were carried out at day 6 and 7 respectively. Results: In the training session, the vehicle injected group was received 7.5±2.56 footshocks in the learning trial. rhEPO (5.5 ± 1.93 footshocks) and asialoEPO (4.86 ± 1.07 footshocks) treated group were less than vehicle group statistically. The latency of the vehicle treated animals to enter the dark compartment (37 ± 54.3 secs) was significantly shorter than rhEPO (230±72.5 secs) and asialoEPO (264 ± 71.9 secs) treated group. AsialoEPO didn't affect bone marrow and didn't increase hemoglobin level. The viable cells in CA1 field were counted by Nissl staining, the rhEPO treated group (103.57 ± 78.91 cells/ mm) and asialoEPO treated group (144.99 ± 92.26 cells/ mm) were significantly suppressed the neuronal cell death than vehicle treated group (19.53±10.72 cells/mm). TUNEL (terminal deoxynucleotidyltransferasemediated 2 0-deoxyuridine 5 0-triphosphate-biotin nick end labeling) staining showed that rhEPO (33.40 ± 23.0 cells/mm) and asialoEPO (25.61 ± 41.96 cells/mm) injection caused a significant reduction than vehicle treatment (76.67 ± 23.02 cells/mm) in the number of CA1 neurons 7 days after ischemia. Conclusion: Multiple dosing of asialoEPO protects hippocampal CA1 neurons from ischemic damage by preventing from falling into apoptosis, and it does not affect erythropoiesis in the bone marrow.

To Use or Not to Use Metformin in Cerebral Ischemia: A Review of the Application of Metformin in Stroke Rodents

“…The different results for the cellular pathways studied in cerebral ischemia indicate that this molecule produces intrinsic neuroprotective factors because it affects the expression of neuroprotective genes, such as vascular endothelial growth factor (VEGF) [72]; affects oxidative stress by activating antioxidant enzymes, such as glutathione peroxidase [57, 84]; induces endogenous transcription factors through the aPKC-CBP pathway [70]; favors the M2 microglial phenotype associated with tissue repair [77]; inhibits cytochrome c release from the mitochondria; and induces neurogenesis in the hippocampus and subventricular zone [25, 72]. …”