The pathologic outcomes and efficacy of epothilone treatment following traumatic brain injury is determined by age
Zhu, Z and Chuckowree, JA and Musgrove, R and Dickson, TC and Blizzard, CA, The pathologic outcomes and efficacy of epothilone treatment following traumatic brain injury is determined by age, Neurobiology of Aging, 93 pp. 85-96. ISSN 0197-4580 (2020) [Refereed Article]
Traumatic brain injury (TBI) can affect individuals at any age, with the potential of causing lasting neurologic consequences. The lack of effective therapeutic solutions and recommendations for patients that acquire a TBI can be attributed, at least in part, to an inability to confidently predict long-term outcomes following TBI, and how the response of the brain differs across the life span. The purpose of this study was to determine how age specifically affects TBI outcomes in a preclinical model. Male Thy1-YFPH mice, that express yellow fluorescent protein in the cytosol of a subset of Layer V pyramidal neurons in the neocortex, were subjected to a lateral fluid percussion injury over the right parietal cortex at distinct time points throughout the life span (1.5, 3, and 12 months of age). We found that the degree of neuronal injury, astrogliosis, and microglial activation differed depending on the age of the animal when the injury occurred. Furthermore, age affected the initial injury response and how it resolved over time. Using the microtubule stabilizing agent Epothilone D, to potentially protect against these pathologic outcomes, we found that the neuronal response was different depending on age. This study clearly shows that age must be taken into account in neurologic studies and preclinical trials involving TBI, and that future therapeutic interventions must be tailored to age.
age at injury, axonal degeneration, cytoskeleton, epothilones, glia, traumatic brain injury