Resveratrol for Intracranial Aneurysm Rupture Prevention

• Mouse models of cerebral aneurysm:
  • In hypertensive mice with induced aneurysms, resveratrol significantly reduced both the number and size of aneurysms.
  • Histological findings: reduced macrophage infiltration and healthier arterial wall thickness.
  • Proposed mechanism: inhibition of the NF‑κB pathway and downregulation of MMP‑2 and MMP‑9.

• Subarachnoid hemorrhage (SAH) models:
  • In rodent SAH models, resveratrol reduced early brain injury, blood–brain barrier disruption, and cerebral edema.

• As of now, no clinical trials have evaluated resveratrol for preventing intracranial aneurysm rupture in humans.
• Existing human studies on resveratrol focus on other diseases (e.g., cardiovascular, metabolic) with mixed or limited efficacy.

• Resveratrol shows promise in animal models but is not currently supported as a preventive treatment for aneurysm rupture in humans.
• Oral resveratrol has low bioavailability (~0.5%) and is rapidly metabolized.
• Potential side effects at high doses include nausea and diarrhea.

• Although preclinical data are encouraging, resveratrol cannot yet be recommended for intracranial aneurysm prevention.
• Patients should continue to follow established medical advice:
  • Control hypertension
  • Avoid tobacco
  • Monitor known aneurysms regularly
  • Discuss aspirin or statin use with a physician

• Stay informed about emerging research and possible clinical trials.
• Consider resveratrol only as a research compound—not a clinical solution—for aneurysm prevention.

Type of study:: In vivo animal study (murine intracranial aneurysm model) First author:: Dang et al. Author affiliations::

• Hamamatsu University School of Medicine, Hamamatsu

1. Dept. of Neurosurgery
2. Dept. of Anesthesia and ICU
3. Dept. of Medical Education
4. Dept. of Pharmacology

• Asahikawa University School of Medicine, Asahikawa

1. Dept. of Anesthesia and ICU

• Hamamatsu Medical Center, Hamamatsu

1. Dept. of Neurosurgery

Journal:: Journal of Neuroscience Research Purpose:: To evaluate whether dietary resveratrol prevents formation or rupture of intracranial aneurysms via anti‑inflammatory mechanisms. Conclusions::

• No significant reduction in aneurysm formation incidence
• Marked reduction in rupture rate (88 % → 40 %, p=0.026)
• Modulation of inflammatory markers: ↑Sirt1, ↓Nfkb1, ↓Tnf

Citation:: ¹⁾

1. Model limitations The elastase + DOCA‑salt murine model poorly reflects human aneurysm pathophysiology, lacking hemodynamic fidelity. No histological validation of aneurysm similarity or wall integrity is presented.

2. Statistical fragility Sample size is small (N not disclosed), likely underpowered. The significant reduction in rupture risk may result from chance due to low event counts. No power analysis provided.

3. Incomplete inflammatory profiling Only mRNA (not protein) levels of Sirt1, Nfkb1, and Tnf were analyzed. No IHC, ELISA, or time-course experiments to demonstrate functional effects or causality.

4. Intervention timing Resveratrol was administered preventively—3 weeks before aneurysm induction. This limits translational relevance as human patients typically present after aneurysm formation.

5. Lacking pharmacokinetics/pharmacodynamics No measurement of serum/tissue levels of resveratrol. Effective concentrations in cerebral vasculature remain speculative.

6. Uncontrolled confounders No report of blood pressure differences between groups, despite using a DOCA‑salt model of induced hypertension.

7. Limited novelty Anti-inflammatory vascular effects of resveratrol are well-documented. This work offers incremental rather than groundbreaking insight.

Flawed design and lack of translational rigor render the study hypothesis-generating at best. The purported protective role of resveratrol lacks mechanistic depth and clinical relevance.

Resveratrol may reduce rupture risk in an artificial murine model, but this does not justify clinical application. Future research must explore post-formation interventions, robust models, and PK/PD validation.

Encouraging data in mice—yet insufficient to warrant human trials.

3/10 – Preliminary and biologically plausible, but weak in methodology and translational relevance.