Treatment of intracerebral hemorrhage in animal models: meta-analysis

Abstract

Objective: Interventions that improve functional outcome after acute intracerebral hemorrhage (ICH) in animals might benefit humans. Therefore, we systematically reviewed the literature to find studies of nonsurgical treatments tested in animal models of ICH.

Methods: In July 2009 we searched Ovid Medline (from 1950), Embase (from 1980), and ISI Web of Knowledge (from 1969) for controlled animal studies of nonsurgical interventions given after the induction of ICH that reported neurobehavioral outcome. We assessed study quality and performed meta-analysis using a weighted mean difference random effects model.

Results: Of 13,343 publications, 88 controlled studies described the effects of 64 different medical interventions (given a median of 2 hours after ICH induction) on 38 different neurobehavioral scales in 2,616 treated or control animals (median 14 rodents per study). Twenty-seven (31%) studies randomized treatment allocation, and 7 (8%) reported allocation concealment; these studies had significantly smaller effect sizes than those without these attributes (p < 0.001). Of 64 interventions stem cells, calcium channel blockers, anti-inflammatory drugs, iron chelators, and estrogens improved both structural outcomes and neurobehavioral scores in >1 study. Meta-regression revealed that together, structural outcome and the intervention used accounted for 65% of the observed heterogeneity in neurobehavioral score (p < 0.001, adjusted r(2) = 0.65).

Interpretation: Further animal studies of the interventions that we found to improve both functional and structural outcomes in animals, using better experimental designs, could target efforts to translate effective treatments for ICH in animals into randomized controlled trials in humans.