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

Abstract

AimTo 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.MethodsFour 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 one-way analysis of variance with post-hoc Tukey test.ResultsNSC 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).ConclusionBeside 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.

Necroptosis is one of the modalities of cell death accompanying ischemic brain stroke: from pathogenesis to therapeutic possibilities

“…Interestingly, we found that neural stem cell transplantation, but also enriched medium, significantly down-regulated Ripk 1. At the same time, neural stem cells did not influence Ripk3 and Mlkl levels, which remains to be explained (24).…”

A call for unification: how to defragment the human brain, medical professions, and national strategies?

“…We wanted to fill the existing gaps by organizing sessions with experts dealing with a particular group of brain diseases or strategies from various angles. For example, amyotrophic lateral sclerosis or stroke can be addressed from the point of view of neuropathology, diagnostics, or neuroinflammation; from the point view of various types of cell death; but also from the point of view of assisted ventilation in the last weeks of patient’s life (3). Every disease can and should be seen from a united point of view: a preclinical scientist is expert in molecular mechanisms and tools to control them, but does not know in what form and when clinical practitioners would require such data.…”