Date of Award


Degree Type


Degree Name

Doctor of Philosophy (PhD)




Traumatic brain injury (TBI) is a major source of disability in modern societies. However, there are no good pharmacological strategies for treating long-term TBI complications because we do not fully understand the injury processes that occur afterward. Moreover, a significant percent of patients entering the emergency room with TBI have a blood alcohol level above the legal limit. Alcohol use and intoxication is a widespread issue in our society. Binge drinking is the most common way in which alcohol is consumed, and alarmingly, Americans of all age groups binge drink on a frequent basis. Despite the prevalence of alcohol intoxication seen together with TBI, how it affects the brain injury and recovery process is not well understood. Our laboratory has previously found that a repeated dose of binge alcohol prior to TBI impairs functional sensorimotor recovery. One means by which the brain responds to injury is the mobilization of neural precursor cells produced by neurogenesis. However, the effect of pre-injury binge alcohol exposure on the reactive neurogenesis that occurs after TBI is not known. Adult neurogenesis is an alternative form of plasticity, which involves the production of new neurons and may contribute to functional recovery after TBI. The subventricular zone (SVZ) is one of the brain’s main neurogenic niches. The experiments in this dissertation therefore sought to determine the short and long term effects of pre-TBI binge alcohol on the neural stem cell responses in the SVZ following brain injury. We assessed the SVZ neural stem cell response after binge alcohol and TBI by utilizing the proliferation marker 5-bromo-2’-deoxyuridine (BrdU) along with other markers for neurogenesis such as Doublecortin. We found that binge alcohol did not affect short and long term lesion size (as measured at 24 hours, 7 days and 6 weeks post TBI). As expected, TBI alone significantly increased SVZ proliferation bilaterally 24 hours post injury. Surprisingly, binge alcohol alone also significantly increased proliferation bilaterally in the SVZ at the 24 hour time point. A combined binge alcohol and TBI regimen resulted in decreased SVZ proliferation bilaterally at 24 hours and 7 days post-TBI. Furthermore, when assessed at 6 weeks after TBI, binge alcohol significantly decreased SVZ neuronal differentiation. While we observed that TBI alone increased migration toward the rostral migratory stream (RMS), binge alcohol did not affect either RMS or perilesional migration post-TBI. Taken together, the results from this dissertation suggest that pre-TBI binge alcohol negatively impacts functional recovery by decreasing short-term neural stem cell proliferative responses as well as long-term neuronal differentiation of these proliferative cells in the SVZ.

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Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.