Brain development in rodents and humans: Identifying benchmarks of maturation and vulnerability to injury across species

Abstract

Hypoxic-ischemic and traumatic brain injuries are leading causes of long-term mortality and disability in infants and children. Although several preclinical models using rodents of different ages have been developed, species differences in the timing of key brain maturation events can render comparisons of vulnerability and regenerative capacities difficult to interpret. Traditional models of developmental brain injury have utilized rodents at postnatal day 7–10 as being roughly equivalent to a term human infant, based historically on the measurement of post-mortem brain weights during the 1970s. Here we will examine fundamental brain development processes that occur in both rodents and humans, to delineate a comparable time course of postnatal brain development across species. We consider the timing of neurogenesis, synaptogenesis, gliogenesis, oligodendrocyte maturation and age-dependent behaviors that coincide with developmentally regulated molecular and biochemical changes. In general, while the time scale is considerably different, the sequence of key events in brain maturation is largely consistent between humans and rodents. Further, there are distinct parallels in regional vulnerability as well as functional consequences in response to brain injuries. With a focus on developmental hypoxicischemic encephalopathy and traumatic brain injury, this review offers guidelines for researchers when considering the most appropriate rodent age for the developmental stage or process of interest to approximate human brain development.

Zika virus infection disrupts neurovascular development and results in postnatal microcephaly with brain damage

“…However, current approaches to model ZIKV infection in rodents results in lethality during pregnancy, although human babies survive and display microcephaly. In addition, a newly born mouse brain is relatively immature, akin to the developmental stage of the human brain at midgestation (Semple et al, 2013), and mouse brain development includes a major postnatal component. Thus, it has been suggested that examination of neurodevelopmental defects of ZIKV in mice requires postnatal analysis (Miner et al, 2016).…”

Prolonged human neural stem cell maturation supports recovery in injured rodent CNS

“…The human gestational period is 280 days; rat gestation is 21 days (11). At birth, the human brain roughly corresponds to a postnatal day 7 rat brain based on body/brain weight ratios, and a 2-to 3-year-old human brain corresponds to a post natal day-20 rat brain (11).…”

“…At birth, the human brain roughly corresponds to a postnatal day 7 rat brain based on body/brain weight ratios, and a 2-to 3-year-old human brain corresponds to a post natal day-20 rat brain (11). Yet most NSC grafting studies have been performed over relatively short survival times of weeks to a few months in vivo (3,5,9,12).…”

Animal Models of Zika Virus Infection, Pathogenesis, and Immunity

“…ZIKV infection has been studied in WT neonatal mice (14,28,46,47). Neonatal mice may be useful models as key brain developmental processes in rodents occur postnatally, in contrast to the case for humans, where they occur during the third trimester of fetal development (48). Infection of 7-to 8-day-old WT C57BL/6 mice with ZIKV Dakar 41519 or ZIKV H/PF/2013 by subcutaneous or intraperitoneal injection resulted in central nervous system pathology and partial lethality (14,28).…”