# Multimodal Neuroprotection in Ischemic Stroke: Emerging Non-Pharmacological Interventions from Bench to Bedside

## TL;DR

This paper reviews non-drug treatments like cooling and oxygen therapy that protect the brain after stroke and could improve recovery.

## Contribution

The paper highlights recent non-pharmacological neuroprotective interventions with clinical potential for ischemic stroke.

## Key findings

- Non-pharmacological interventions like hypothermia and hyperoxia show high safety and tolerability.
- These methods can be used alongside revascularization therapies to improve stroke outcomes.
- Clinical trials support their potential to enhance neurological recovery in stroke patients.

## Abstract

Currently, the effective therapeutic strategies for acute ischemic stroke (AIS) remain revascularization therapies, including intravenous thrombolysis and endovascular thrombectomy. However, the narrow time window and reperfusion injury associated with reperfusion therapy limit favorable outcomes in some patients. As adjuncts to revascularization, certain neuroprotective agents have demonstrated robust preclinical results, but only a few have achieved successful clinical translation due to challenges in dosing and safety concerns. In recent years, convenient and relatively safe non-pharmacological neuroprotective interventions—such as hypothermia, remote ischemic conditioning (RIC), and normobaric hyperoxia (NBO)—have gained increasing research attention. These approaches offer advantages including high safety profiles, excellent tolerability, low cost, and the potential to synergize with reperfusion therapy, underscoring their broad clinical applicability. Numerous clinical trials have validated their potential to improve neurological functional outcomes, and this review explores the mechanisms and clinical applications of non-pharmacological neuroprotective therapies in ischemic stroke.