HIF‐1α promotes bone marrow stromal cell migration to the injury site and enhances functional recovery after spinal cord injury in rats

Abstract

Background Spinal cord injury (SCI) is a severe health problem worldwide, and efficacious strategies to properly repair SCI have not yet been developed. Recently, gene and cell therapies as alternative treatments for SCI have been proposed to comprise safe and promising strategies. Methods The present study investigated the therapeutic effects and underlying mechanisms of hypoxia‐inducible factor‐1α carried in recombinant adenovirus (Adv‐HIF‐1α), as administered immediately after SCI in adult rats. Results Adv‐HIF‐1α‐treated animals showed better functional recovery and smaller cavity volume than those in the vehicle‐treated control group. Both the numbers of green fluorescent protein‐labeled bone marrow stromal cells (GFP‐BMSCs) and cells double‐positive for GFP and a cell lineage marker (NeuN) in the injured spinal cord were larger in the Adv‐HIF‐1α‐treated group. The expression levels of neurotrophins such as neurotrophin‐3 and brain‐derived neurotrophic factor were also higher in the Adv‐HIF‐1α‐treated group. Conclusions Adv‐HIF‐1α improves functional recovery in rats with SCI, and the underlying mechanism may be related to the mobilization of BMSCs to the injured area and higher expression levels of neurotrophin‐3 and brain‐derived neurotrophic factor.

PGK1 Is Involved in the HIF-1 Signaling Pathway as a Hub Gene for Ferroptosis After Traumatic Brain Injury

“…The HIF-1 signaling pathway is involved in the cellular response to hypoxia; high expression of HIF-1 facilitates neurological recovery in mice [33,34]. The effect of HIF-1 on ferroptosis is achieved through the induction of transcription of fatty acid binding protein 3 and fatty acid binding protein 7 [26].…”

Identification of Ferroptotic Genes in Spinal Cord Injury at Different Time Points: Bioinformatics and Experimental Validation

“…Hypoxia inducible factor-1 (HIF-1) signaling pathway is involved in the cellular response to hypoxia. Elevation expression of HIF-1 bene ts neurological recovery in SCI rats [32,33]. And the negative effect of HIF-1 on ferroptosis was implemented via inducing transcription of fatty acid binding protein 3 and fatty acid binding protein 7 [34].…”