# Adipose-derived stem cell-conditioned medium mitigates ischemia-induced neuronal injury via the JAK1/STAT3 signaling pathway

## TL;DR

This study shows that a substance from fat cells protects brain cells from stroke damage by activating a specific signaling pathway.

## Contribution

The study identifies the JAK1/STAT3 pathway as the key mechanism behind the neuroprotective effects of ADSC-conditioned medium.

## Key findings

- ADSC-CM improved neurological function and reduced brain damage in stroke rats.
- ADSC-CM activated the JAK1/STAT3 pathway in both in vivo and in vitro models.
- Blocking JAK1/STAT3 eliminated the protective effects of ADSC-CM.

## Abstract

Adipose-derived stem cells (ADSCs) demonstrate therapeutic potential for ischemic stroke, primarily through paracrine actions. However, the specific intracellular signaling pathways underlying these benefits remain unclear. This study investigates the critical role of JAK1/STAT3 signaling in neuroprotection mediated by ADSC-conditioned medium (ADSC-CM).

We employed a dual-model approach. In vivo, rats subjected to transient middle cerebral artery occlusion (tMCAO) received intravenous ADSC-CM or vehicle at 2, 24, and 48 h post-ischemia, with or without the JAK1 inhibitor GLPG0634. Neurological function was evaluated over a period of 7 days. Subsequently, infarct volume, brain edema, neuronal survival, neurovascular regeneration, synaptic ultrastructure, mitochondrial function, and energy metabolism were analyzed. In vitro, primary cortical neurons subjected to oxygen–glucose deprivation (OGD) were treated with ADSC-CM with or without GLPG0634 to assess neurite outgrowth. Activation of the JAK1/STAT3 pathway was confirmed by Western blot in both models.

In vivo, ADSC-CM significantly improved neurological function, reduced infarct volume and brain edema, and enhanced neuronal survival, nerve fiber regeneration, angiogenesis, synaptic plasticity, and mitochondrial function in tMCAO rats. In vitro, ADSC-CM promoted neurite outgrowth in OGD-injured neurons. Crucially, all these multifaceted neuroprotective effects were completely abolished by co-treatment with GLPG0634. Mechanistically, ADSC-CM robustly activated JAK1 and STAT3 phosphorylation in both models, an effect effectively inhibited by GLPG0634.

The neuroprotective effects of ADSC-CM are mechanistically linked to the activation of the JAK1/STAT3 pathway, which mitigates ischemic damage by promoting neuronal salvage, neurovascular regeneration, synaptic plasticity, and metabolic recovery, thereby enhancing neurological functional recovery after stroke.