Biomolecules· 2026Q1
Beyond Recanalization: Neurovascular Unit Protection and Precision Adjunctive Therapy for Ischemic Stroke in the Reperfusion Era
- 0citations
- Q1SCImago
- 2026year
Short summary
Adjunctive therapies for ischemic stroke should target the neurovascular unit (NVU) to bridge the gap between macrovascular recanalization and functional recovery, rather than focusing solely on neuronal survival.
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Key points
- Macrovascular reopening in ischemic stroke does not guarantee tissue reperfusion or functional recovery due to microvascular no-reflow and neurovascular unit (NVU) injury.
- Classical neuroprotection failed due to model mismatches, timing issues, and oversimplification of ischemic injury.
- Effective cerebroprotection in the reperfusion era must target the NVU across different stages: pre-recanalization, during thrombectomy, and post-reperfusion.
- A precision framework is proposed, integrating tissue/target windows, reperfusion status, and measurable treatment response for adjunctive therapies.
AI-generated from the title and abstract; the full text is not read.
Abstract
Intravenous thrombolysis and endovascular thrombectomy (EVT) have increased large-vessel recanalization in acute ischemic stroke, yet macrovascular reopening does not ensure tissue reperfusion or functional recovery. Microvascular no-reflow, blood–brain barrier failure, oxidative injury, thromboinflammation, edema, and hemorrhagic transformation sustain a recanalization-to-recovery gap. Classical neuroprotection failed because of mismatches in models, timing, brain exposure, patient selection, and endpoints, and because ischemic injury was reduced to a single neuronal pathway. Cerebroprotection in the reperfusion era should target the neurovascular unit: delaying penumbral collapse before recanalization, limiting oxidative and vascular injury during thrombectomy, and restoring microcirculatory and barrier function afterwards. Recent trials show a differentiated landscape. ESCAPE-NEXT and RODIN were neutral; TASTE-2 suggested a borderline overall effect and imaging-defined heterogeneity for edaravone dexborneol; BAST supported potential benefit from butylphthalide; and the positive EMPHASIS trial contrasted with neutral EVT-specific MIST-A findings for minocycline. We organize mechanisms and interventions along the macrovascular recanalization–tissue reperfusion–neurovascular-unit preservation–functional recovery continuum, stratify evidence across pharmacological, physiological, delivery, natural-product, and cell/extracellular-vesicle strategies, and propose a precision framework integrating tissue and target windows, reperfusion status, and measurable treatment response. Next-generation trials should combine target engagement, imaging enrichment, prespecified biomarker interactions, and adaptive designs. Current evidence supports redesigning cerebroprotection, not adopting any candidate as a universal adjunct to reperfusion.
The authors' abstract, as published at the source. Biomolecules, 2026 · DOI ↗
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Field: Neurology (Neuroscience)
NeurologyNeuroscience