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

Prog Neurobiol. 2013 Jul-Aug:106-107:1-16. doi: 10.1016/j.pneurobio.2013.04.001. Epub 2013 Apr 11.


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 hypoxic-ischemic 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.

Keywords: 5-HT; 5-hydroxytryptamine; Agamma-Aminobutyric acid; Brain development; CNS; Central nervous system; GAB; GCL; Gd; HI; HIE; Human; Hypoxia-ischemia; IL; Immature; MRI; N-methyl-D-aspartate; NMDA; OL; Rodent; SGZ; SVZ; TBI; Traumatic brain injury; gestation day; granule cell layer; hypoxia-ischemia/hypoxic-ischemic; hypoxic-ischemic encephalopathy; interleukin; magnetic resonance imaging; oligodendrocyte; pnd; postnatal day; pre-OL; pre-oligodendrocyte; subgranular zone; subventricular zone; traumatic brain injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain / growth & development*
  • Brain / physiopathology*
  • Brain Injuries / physiopathology*
  • Humans
  • Hypoxia-Ischemia, Brain / physiopathology
  • Neurogenesis / physiology*
  • Oligodendroglia / physiology
  • Rodentia