engleski

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

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 apoptosis – 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 downregulated 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.

MCAO stroke model ; Stem cell transplantation ; programmed cell death

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