Neurologic impairment following closed head injury predicts post-traumatic neurogenesis

Abstract

In the mammalian hippocampus, neurogenesis persists into adulthood, and increased generation of newborn neurons could be of clinical benefit following concussive head injuries. Post-traumatic neurogenesis has been well documented using “open” traumatic brain injury (TBI) models in rodents; however, human TBI most commonly involves closed head injury. Here we used a closed head injury (CHI) model to examine post-traumatic hippocampal neurogenesis in mice. All mice were subjected to the same CHI protocol, and a gross-motor based injury severity score was used to characterize neurologic impairment one hour after the injury. When analyzed 2 weeks later, post-traumatic neurogenesis was significantly increased only in mice with a high degree of transient neurologic impairment immediately after injury. This increase was associated with an early increase in c-fos activity, and subsequent reactive astrocytosis and microglial activation in the dentate gyrus. Our results demonstrate that the initial degree of neurologic impairment after closed head injury predicts the induction of secondary physiologic and pathophysiologic processes, and that animals with severe neurologic impairment early after injury manifest an increase in post-traumatic neurogenesis in the absence of gross anatomic pathology.

Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer’s disease

“…The age-related decline in neurogenesis is also accompanied by an age-related decline in cognitive function (Bolognin et al, 2014). Alterations in hippocampal neurogenesis have also been reported in a number of neurodegenerative diseases (AD and Huntington's disease) (Choi et al, 2014a;Moon et al, 2014;Perry et al, 2012), neurological diseases (epilepsy, ischaemia and traumatic brain injury) (D'Alessio et al, 2015;Matsuda et al, 2015;Villasana et al, 2014) and neuropsychiatric conditions (stress and depression) (Boldrini et al, 2012;Lucassen et al, 2015;Miller and Hen, 2015). Deficits in cognitive function have also been reported in some of these conditions.…”

Endogenous neurogenic cell response in the mature mammalian brain following traumatic injury

“…Studies from our lab and others have shown that TBI significantly increases cell proliferation in both the SVZ and DG in adult mice and rats in varying TBI models including fluid percussive injury (FPI) (Chirumamilla et al, 2002; Rice et al, 2003), controlled cortical impact injury (CCI) (Dash et al, 2001; Gao et al, 2009), closed head weight drop injury (Villasana et al, 2014) and acceleration-impact injury (Bye et al, 2011). Common to all reported TBI models, the most prominent endogenous cell response in both the DG and SVZ following TBI is an increase in cell proliferation.…”

“…As for the degree of neuronal differentiation, different results have been reported. In diffuse injury models such as the closed head weight drop model and the fluid percussion model, an increased total number of new neurons in the subgranule zone and granule cell layer of the DG were observed following injury (Sun et al, 2007; Villasana et al, 2014). Whereas in a focal injury model such as CCI, the number of new neurons generated following TBI was not significantly increased as compared to sham control despite enhanced cell proliferation (Gao and Chen, 2013).…”

“…For example, in the CCI model, TBI induces significant death of immature neurons in the DG at an early time post-injury before injury-enhanced cell proliferation is observed (Rola et al, 2006; Gao et al, 2008). However, in a closed head diffuse injury model, increased hippocampal neurogenesis in both cell proliferation and generation of new neurons is only observed in the more severely injured animals (Villasana et al, 2014). Despite these differences, it is clear that TBI stimulates activation of endogenous neural stem cells in the neurogenic regions in the mature rodent brain.…”

Altered hippocampal neurogenesis during the first 7 days after a fluid percussion traumatic brain injury

“…12,[24][25][26] Notably, the severity and/or type of injury was found to impact differential changes in hippocampal neurogenesis, 12 and altered neurogenesis was found to be associated with cognitive impairment. [27][28][29] Interestingly, Robinson et al 11 used the same model as in the current study and found no significant differences in the DCX-labeled cells in the dentate gyrus at 30 d after an FPI. 11 There are several possible explanations for this discrepancy.…”