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Updated: Jan 28, 2026
An In Vivo Assessment of Blood-Brain Barrier Disruption in a Rat Model of Ischemic Stroke
Published on: March 11, 2018
Ischemic stroke neuroprotection revisited: translational barriers and a phase-resolved, biomarker-anchored framework
Sam Seok Cho1,2, Eun Jin Shin1,2,3, Yun Gyeong Kim1,2,3
1Department of Biomedical Science, College of Natural Science, Chosun University, Gwangju, 61452, Republic of Korea.
Abstract:
Despite extensive research defining the molecular cascades of ischemic stroke, including excitotoxicity, oxidative stress, inflammation, blood-brain barrier disruption, and regulated cell death, translation of neuroprotective strategies into effective clinical therapies has remained largely unsuccessful. Growing evidence suggests that this gap reflects recurring limitations in translational design rather than insufficient mechanistic insight, including phase-inappropriate intervention, narrow therapeutic windows, inadequate brain exposure, and lack of target engagement in heterogeneous patient populations. In this review, we critically examine why biologically plausible targets have failed to produce clinical benefit by synthesizing lessons from preclinical and clinical studies. We identify common patterns of translational failure and propose a phase-resolved, biomarker-anchored framework that prioritizes therapeutic actionability according to disease stage and neurovascular context. By repositioning biomarkers as tools for patient stratification, risk prediction, and confirmation of target engagement, this framework supports rational sequencing from hyperacute reperfusion support to stage-matched neurovascular and immune modulation and subsequent neurorestorative strategies. This decision-oriented perspective aims to guide more effective trial design and improve translational success in ischemic stroke.
Insights
Translating neuroprotective drugs for ischemic stroke (IS) into clinical success is challenging. This review proposes a new framework using biomarkers to guide treatment timing and patient selection for better trial outcomes.
Area of Science:
- Neuroscience
- Translational Medicine
- Stroke Research
Background:
- Extensive research details ischemic stroke (IS) molecular pathways like excitotoxicity and inflammation.
- Despite mechanistic insights, neuroprotective therapies have largely failed in clinical translation.
- Key translational gaps include inappropriate timing, narrow therapeutic windows, and poor target engagement.
Purpose of the Study:
- To critically analyze reasons for the failure of biologically plausible targets in IS clinical trials.
- To propose a novel framework for improving the design and success rate of IS clinical trials.
- To reframe the role of biomarkers in guiding therapeutic strategies for IS.
Main Methods:
- Synthesis of lessons learned from preclinical and clinical studies in IS research.
- Identification of common patterns contributing to translational failures.
- Development of a phase-resolved, biomarker-anchored framework for therapeutic actionability.
Main Results:
- Recurring limitations in translational design hinder clinical success for IS neuroprotection.
- A proposed framework prioritizes therapeutic interventions based on disease stage and neurovascular context.
- Biomarkers can be leveraged for patient stratification, risk prediction, and target engagement confirmation.
Conclusions:
- Rethinking translational strategies is crucial for advancing IS neuroprotection.
- A biomarker-guided, stage-specific approach can optimize clinical trial design.
- This framework aims to improve the success rate of neuroprotective therapies in ischemic stroke.
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