Transplantation of neural stem cells in the mouse model of ischemic brain stroke and expression of genes involved in programmed cell death

Abstract

Aim: To analyze how neural stem cells (NSC) transplantation in the stroke-affected mouse brain influences the expression of genes involved in apoptosis-inducing factor (AIF)-mediated cell death - apoptosis inducing factor mitochondria associated 1 (Aifm1), ring finger protein 146 (Rnf146, Iduna), and cyclophilin A (CypA); necroptosis-receptor interaction protein kinase 1 (Ripk1), Ripk3, and mixed-lineage kinase domain-like protein (Mlkl); and apop-tosis - Caspase 3 (Casp3) and Casp8. Methods: Four groups of animals were used to obtain mRNA for quantitative reverse transcription polymerase chain reaction analysis: healthy animals (n = 3), animals with stroke (n = 4), animals with stroke treated by stem cell transplantation (n = 7), and animals with stroke treated by proliferation-supporting medium (n = 5). Ischemic brain injury was induced by transient left middle cerebral artery occlusion. Statistical analysis was performed using oneway analysis of variance with post-hoc Tukey test. Results: NSC transplantation in the stroke-affected mouse brain significantly increased the expression of Iduna (P < 0.05), a gene-encoding protein with well-known protective effects on hypoxic damage, and significantly down-regulated the expression of damage-supportive genes, Casp3 (P < .01) and Aifm1 (P < 0.001). We were able to distinguish between the effect produced by stem cell transplantation (Iduna, Aifm1, Ripk3, Mlkl) and the effect produced by supporting the tissue with proliferation-supporting medium (Ripk1, Casp8). Conclusion: Beside revealing some clearly positive effects of stem cells transplantation on the stroke-affected brain, our results suggest that the tissue response triggered by stem cells points toward the desired, regeneration-supporting levels of expression of a certain gene at a certain time point.