Abstract Body: The first Stroke Preclinical Assessment Network (SPAN 1) tested 6 therapeutic interventions initiated at the time of reperfusion in models of focal ischemic stroke, including models of cardiovascular risk factors. To improve preclinical testing rigor and reproducibility, the testing was conducted as a large, randomized controlled trial across 6 sites with a coordinating center that concealed treatments and blinded neurobehavior video assessments. The trial had an adaptive design with preset levels of efficacy and futility interrogated after each of 4 stages relative to placebo (P). The primary outcome was turning preference on the corner test at 30 days. Secondary outcomes included corner test turns at 7 days, foot-faults on a grid walk test at 7 and 30 days, and MRI lesion volume at 2 and atrophy at 30 days. Based on the primary outcome data pooled from young mice, aging mice, high-fat diet obese mice and spontaneously hypertensive rats (SHRs), the poly(ADP-ribose) polymerase (PARP) inhibitor, veliparib (V), was considered futile after the second stage (V=271; P=171). Here, we performed a secondary analysis of the veliparib data on individual subgroup models, secondary outcomes, and effects of sex. Veliparib (10 mg/kg) injected IV at reperfusion failed to show a benefit on the corner test or grid walk test at 7 or 30 days of recovery or a reduction in lesion volume in young mice (V=114; P=56), obese mice (V=38; P=34), or SHRs (V=39; P=41). However, in aging mice (17-18-months-old; V=39; P=40), veliparib significantly improved performance on the corner test (P = 0.009) and grid walk test (P = 0.002) at 7 days; the benefit was independent of sex. However, mortality in the aging mice was greater than in the other subgroup models at all sites, and significance in the corner test was lost at 30 days (P = 0.10) associated with the decreased sample size. Aging mice were especially susceptible to respiratory arrest during anesthesia while conducting MRI scans. Lesion volume at 2 days was small in the veliparib (2-3% of hemisphere) and placebo (4%) groups, suggesting that the benefit of veliparib on neurobehavior might be due to its known anti-inflammatory effects rather than by decreasing infarct volume. Because ischemic stroke predominantly occurs in the aging population, further research into the neurobehavior benefit of PARP inhibitors in aged animal models of stroke is warranted in protocols that omit post-ischemic anesthesia so as to improve survival.