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Multicenter Stroke Preclinical Assessment Network Analysis of Cardiovascular Risk Factor Subgroups Treated With the

Raymond C Koehler1, Karni Bedirian2, Mu-Hsun Chen2

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|September 25, 2025
PubMed
Summary

Poly(ADP-ribose) polymerase (PARP) inhibitor veliparib showed no benefit in young, obese mice, or rats after stroke. However, veliparib improved functional recovery in aging mice, suggesting potential for aged stroke models.

Keywords:
agingmiddle cerebral artery occlusionobesitypoly(ADP‐ribose) polymerasepreclinical trialspontaneously hypertensive ratveliparib

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Stroke Research

Background:

  • The Stroke Preclinical Assessment Network (SPAN) evaluated six interventions for focal ischemic stroke.
  • This trial utilized a randomized, controlled design across six sites with concealed treatment and blinded assessments.
  • The PARP inhibitor veliparib was initially deemed futile across pooled animal models.

Purpose of the Study:

  • To conduct a secondary analysis of veliparib's efficacy in individual animal models of ischemic stroke.
  • To evaluate veliparib's impact on primary and secondary neurobehavioral outcomes in specific preclinical stroke subgroups.

Main Methods:

  • Secondary analysis of a randomized, controlled trial involving young mice, aging mice, obese mice, and spontaneously hypertensive rats.
  • Veliparib administered intravenously at reperfusion; primary outcome was corner test turning preference at 1 month.
  • Neurobehavioral assessments included the corner test and grid walk test.

Main Results:

  • Veliparib did not improve corner test performance in young mice, obese mice, or rats.
  • Aging mice (15-18 months) showed significant improvements in corner test performance and reduced foot-faults on the grid walk test with veliparib.
  • No significant effects of veliparib on lesion volume or survival were observed across models, though mortality was high in aging mice.

Conclusions:

  • Veliparib demonstrated significant functional benefits in aging mice following ischemic stroke.
  • Given stroke's prevalence in the aging population, further investigation of PARP inhibitors in aged stroke models is warranted.
  • These findings highlight the potential of targeted therapies for stroke in older individuals.