Repeated Mild Traumatic Brain Injury

Cell Transplantation

Traumatic Brain Injury

Brooke Fehily¹  Melinda Fitzgerald² 

[1] Experimental and Regenerative Neurosciences, School of Biological sciences, The University of Western Australia, Perth, Western Australia, Australia;Experimental and Regenerative Neurosciences, School of Biological sciences, The University of Western Australia, Perth, Western Australia, Australia;Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia;Perron Institute for Neurological and Translational Science, Sarich Neuroscience Research Institute, Nedlands, Western Australia, Australia;

关键词: repeated mild traumatic brain injury;    pathology;    functional deficits;    reactive gliosis;    oxidative stress;    myelin abnormalities;   

DOI  :  10.1177/0963689717714092

 received in 2016-07-04, accepted in 2016-08-01,  发布年份 2017

来源: Sage Journals

【 摘 要 】

Mild traumatic brain injury (mTBI) represents a significant public healthcare concern, accounting for the majority of all head injuries. While symptoms are generally transient, some patients go on to experience long-term cognitive impairments and additional mild impacts can result in exacerbated and persisting negative outcomes. To date, studies using a range of experimental models have reported chronic behavioral deficits in the presence of axonal injury and inflammation following repeated mTBI; assessments of oxidative stress and myelin pathology have thus far been limited. However, some models employed induced acute focal damage more suggestive of moderate–severe brain injury and are therefore not relevant to repeated mTBI. Given that the nature of mechanical loading in TBI is implicated in downstream pathophysiological changes, the mechanisms of damage and chronic consequences of single and repeated closed-head mTBI remain to be fully elucidated. This review covers literature on potential mechanisms of damage following repeated mTBI, integrating known mechanisms of pathology underlying moderate–severe TBIs, with recent studies on adult rodent models relevant to direct impact injuries rather than blast-induced damage. Pathology associated with excitotoxicity and cerebral blood flow-metabolism uncoupling, oxidative stress, cell death, blood-brain barrier dysfunction, astrocyte reactivity, microglial activation, diffuse axonal injury, and dysmyelination is discussed, followed by a summary of functional deficits and preclinical assessments of therapeutic strategies. Comprehensive characterization of the pathology underlying delayed and persisting deficits following repeated mTBI is likely to facilitate further development of therapeutic strategies to limit long-term sequelae.

【 授权许可】

CC BY-NC   
© The Author(s) 2017

【 图 表 】

Figure 10