Elderly individuals are particularly vulnerable to the damaging effects of traumatic brain injury (TBI).  From age 65, TBI incidence rates double for every additional 10 years of age. Increasing literature reports clinically worse outcomes in elderly TBI patients, and long-term functional recovery is poorer in elderly TBI survivors when compared to younger survivors.  However, research on the underlying mechanisms responsible for poorer outcomes in elderly TBI patients is severely limited.

Experimental studies have demonstrated that compared to young adult animals, TBI in aged animals results in greater impairments in bioenergetic function, diminished HIF1α signaling, increased oxidative stress, and increased blood brain barrier permeability.  Notably, post-traumatic neuroinflammation is also significantly impacted by aging, and aged TBI animals have a more pronounced and prolonged glial cell activation in the hippocampus when compared to young TBI animals.  Our recent work has demonstrated that aging increases microglial sensitivity to TBI by altering cell proliferation potential, oxidative stress responses, phagocytic behavior, and cytokine profile.  These age-related impairments in neuroimmune function were accompanied by deficits in muscle strength, locomotor activity, endurance level, and motor coordination (see Ritzel et al., Neurobiology of Aging, 77:194–206, 2019 for details).  

We previously demonstrated that TBI causes increased neurodegeneration and microglial activation in the cortex, hippocampus and thalamus of aged animals, when compared to young TBI animals (see Kumar et al., Neurobiology of Aging, 34:1397-411, 2013 for details).  Future research will investigate the underlying molecular mechanisms that contribute to increased microglial activation and associated neurotoxicity in the aged brain following TBI. It is proposed that increased NADPH oxidase activity during aging alters the activation status of microglia from favoring an anti-inflammatory state in young, to a pro-inflammatory state in elderly.  This shift towards a pro-inflammatory state will result in increased neurodegeneration and worse neurological outcomes in the elderly.  Genetic and pharmacological intervention studies in young and aged TBI mice are currently being performed to rigorously test this hypothesis.