It is widely held that injured neurons in the central nervous system do not have the capacity to undergo axonal regeneration. Recently, however, there is mounting evidence that serotonin fibers are an exception to this rule. Serotonin fibers undergo long-distance regeneration in the neocortex after amphetamine lesion. They can also traverse the rift created by a penetrating injury in the neocortex. These new fibers are indistinguishable in morphology from spared axons and have been shown to be competent to release serotonin. While experimentally useful, these models do not mimic the most typical clinical injuries. Traumatic brain injury (TBI) is prevalent and can lead to pathologies such as depression that are a result of serotoninergic dysfunction. So whether serotonin fibers can regrow after TBI is an important question. To address this, we used a controlled cortical impact (CCI) model to evoke injury in adult mouse neocortex and assessed serotonin fiber innervation one week, one month, and three months after injury with immunohistochemistry. In the neocortex serotonin fibers traverse in an anterior to posterior direction. CCI, as well as an open skull injury without impact, resulted in decreases in serotonin fiber innervation posterior to the injury site one week after surgery. At one month and three months after surgery there was a significant regrowth of serotonin fibers posterior to the injury. We also quantified reactive astrocytes following TBI using GFAP immunohistochemistry. There was profound reactive astrogliosis one week after surgery that decreased close to control levels by three months. Interestingly, the amount of reactive gliosis was not correlated to the amount of serotonin fiber loss in either regions anterior or posterior to the injury. Microglial density was not affected by TBI. In addition, we investigated whether a repetitive mild TBI model leads to serotonin fiber loss in mouse neocortex. We did not detect serotonin fiber loss across a range of injury severities despite the presence of reactive gliosis in the optic fiber tract accompanying these injuries. These findings indicate that serotonin fibers can be damaged in certain clinically relevant TBI models and are capable of regrowth following injury
