Is the ferret a suitable species for studying perinatal brain injury?

Abstract

Complications of prematurity often disrupt normal brain development and/or cause direct damage to the developing brain, resulting in poor neurodevelopmental outcomes. Physiologically relevant animal models of perinatal brain injury can advance our understanding of these influences and thereby provide opportunities to develop therapies and improve long-term outcomes. While there are advantages to currently available small animal models, there are also significant drawbacks that have limited translation of research findings to humans. Large animal models such as newborn pig, sheep and nonhuman primates have complex brain development more similar to humans, but these animals are expensive, and developmental testing of sheep and piglets is limited. Ferrets (Mustela putorius furo) are born lissencephalic and undergo postnatal cortical folding to form complex gyrencephalic brains. This review examines whether ferrets might provide a novel intermediate animal model of neonatal brain disease that has the benefit of a gyrified, altricial brain in a small animal. It summarizes attributes of ferret brain growth and development that make it an appealing animal in which to model perinatal brain injury. We postulate that because of their innate characteristics, ferrets have great potential in neonatal neurodevelopmental studies.

Keywords: Animal model; Ferrets; Neurodevelopment; Neurogenesis; Perinatal brain injury.

Fig. 1

Comparison of ferret and human cortical maturation timelines for several critical events in corticogenesis. Abbreviations: E-embryonic day; P-postnatal day; GW-gestational week.

Fig. 2

Comparison of rat, ferret and Macaque nemestrina brains at term equivalence, demonstrating the presence of gyri in ferrets and nonhuman primates, as well as an increase in white to gray matter ratios in ferrets and primates compared to rodent brain. The horizontal line below each brain shows a 1 cm marker for scale. GM denotes gray matter, WM denotes white matter, and hip indicates the location of the hippocampus in each coronal brain section.