Neuritin-overexpressing transgenic mice demonstrate enhanced neuroregeneration capacity and improved spatial learning and memory recovery after ischemia-reperfusion injury

Abstract

Acute ischemia-reperfusion (IR)-induced brain injury is further exacerbated by a series of slower secondary pathogenic events, including delayed apoptosis due to neurotrophic factor deficiency. Neuritin, a neurotrophic factor regulating nervous system development and plasticity, is a potential therapeutic target for treatment of IR injury. In this study, Neuritin-overexpressing transgenic (Tg) mice were produced by pronuclear injection and offspring with high overexpression used to generate a line with stable inheritance for testing the neuroprotective capacity of Neuritin against transient global ischemia (TGI). Compared to wild-type mice, transgenic mice demonstrated reduced degradation of the DNA repair factor poly [ADP-ribose] polymerase 1 (PARP 1) in the hippocampus, indicating decreased hippocampal apoptosis rate, and a greater number of surviving hippocampal neurons during the first week post-TGI. In addition, Tg mice showed increased expression of the regeneration markers NF-200, synaptophysin, and GAP-43, and improved recovery of spatial learning and memory. Our findings exhibited that the window of opportunity of neural recovery in Neuritin transgenic mice group had a tendency to move ahead after TGI, which indicated that Neuritin can be used as a potential new therapeutic strategy for improving the outcome of cerebral ischemia injury.

Neuronal Differentiation and Outgrowth Effect of Thymol in Trachyspermum ammi Seed Extract via BDNF/TrkB Signaling Pathway in Prenatal Maternal Supplementation and Primary Hippocampal Culture

“…com/article/10.3390/ijms24108565/s1. References [55][56][57][58][59][60][61] are cited in the Supplementary Materials. Informed Consent Statement: Not applicable.…”

Wirelessly Powered‐Electrically Conductive Polymer System for Stem Cell Enhanced Stroke Recovery

“…Results suggest that the cells were viable after electrical stimulation (Figure 4b); which corroborates with prior study results utilizing identical parameters delivered via a wired system. [8,12] Evaluation of gene expression changes after stimulation via quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed that certain genes implicated in stroke recovery, vascular endothelial growth factor B (VEGFB) and neuritin-1 (NRN1), which are crucial for blood vessel formation and neural regeneration, [22,23] respectively, were upregulated in comparison to unstimulated control cells (Figure 4c). This data supports findings from prior work, [8,11] where a similar effect is demonstrated with the tethered stem cell scaffold system, indicating that this novel wireless powered system can confer analogous results.…”

Therapeutic Potential of Remote Ischemic Conditioning in Vascular Cognitive Impairment

“…Numerous mechanisms underly the protective effect of RIC on neurons, and the suppression of apoptosis might be one of them. Neuronal apoptosis is a crucial pathological change in cognitive function associated with acute or chronic cerebral hypoperfusion ( Poh et al, 2020 ; Wan et al, 2020 ), which is characterized by downregulation of anti-apoptotic Bcl-2, upregulation of pro-apoptotic Bax, and activation of caspases ( Wang X. X. et al, 2020 ). Thereby, anti-apoptosis is considered a target for VCI.…”