Translational Intracerebral Hemorrhage: a Need for Transparent Descriptions of Fresh Tissue Sampling and Preclinical Model Quality

Abstract

For years, strategies have been proposed to improve translational success in stroke research by improving the quality of animal studies. However, articles that report preclinical intracerebral hemorrhage (ICH) studies continue to lack adequate qualitative and quantitative descriptions of fresh brain tissue collection. They also tend to lack transparency about animal model quality. We conducted a systematic review of 82 ICH research articles to determine the level of detail reported for brain tissue collection. We found that only 24 (29%) reported the volume, weight, or thickness of tissue collected and a specific description of the anatomical location. Thus, up to 71% of preclinical ICH research articles did not properly define how fresh specimens were collected for biochemical measurements. Such omissions may impede reproducibility of results between laboratories. Although existing criteria have improved the quality of preclinical stroke studies, ICH researchers need to identify specific guidelines and strategies to avoid pitfalls, minimize bias, and increase reproducibility in this field.

Alternative activation-skewed microglia/macrophages promote hematoma resolution in experimental intracerebral hemorrhage

“…Fresh 1-mm brain slices were prepared based on established standard procedure (Chang et al, 2015). Images of the brain slices were digitalized by scanner (600 dpi; Epson Perfection V750 PRO) and analyzed with Image J software (NIH, Bethesda, MD).…”

“…Brains were removed, and 4-mm fresh coronal perihematomal tissue sections were collected and processed in ice-cold PBS according to our established method (Chang et al, 2015). CD11b-positive cells were isolated and purified according to published protocol (Bedi et al, 2013; Garcia et al, 2014; Taetzsch et al, 2015), and cell sorting was carried out with cells pooled from three mice per experiment.…”

Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage

“…Fresh 1-mm coronal slices across the whole brain were prepared based on our standard procedure (90). For the histological assessment of hematoma volume, images of the brain slices were digitalized by a scanner (600 dpi) and analyzed with ImageJ software (NIH).…”

“…Alternatively, hemoglobin content in the hemorrhagic brains quantified hematoma volume (91,92). Briefly, 4-mm coronal brain slices across the hemorrhagic territory were collected (90) and homogenized in 300 μl of distilled water. To generate a standard curve, whole blood was obtained by cardiac puncture of anaesthetized intact mice.…”

Building Robustness into Translational Research

“…Therefore, the idea of enhancing robustness of nonclinical studies is not new and has been advocated for more than 20 years (Hsu 1993; Stroke Therapy Academic Industry Roundtable (STAIR) 1999). Nonetheless, poor technical quality and reporting issues remain abundant (Chang et al 2015;Kilkenny et al 2009), and clinical development programs continue to fail due to lack of efficacy despite promising findings in animals. Generalizability shows how applicable the results from one model are for others.…”