Brain-Derived Neurotrophic Factor (BDNF) and Traumatic Brain Injury (Head and Spinal)

摘要

The long term objective of this study was to improve functional outcomes following traumatic brain injury (TBI) by investigating potential mechanisms of neuroprotection. Brain-derived neurotrophic factor (BDNF) has a well-established role in promoting cell survival during development. Using a well characterized animal model of TBI, the lateral fluid percussion (FP) brain injury model, we first characterized acute alterations in gene expression of BDNF and its receptor, trkB in response to injury. This study demonstrated that regions of the brain that are resistant to cell damage have increased gene expression for BDNF and its high affinity receptor, tyrosine kinase B (trkB) during the acute periods after injury. Study 2 examined whether the alterations in mRNA levels following FP injury resulted in subsequent alterations in protein levels of BDNF and trkB and activation of the ERK/MAP kinase signal transduction pathway. In contrast to the robust changes in BDNF mRNA levels, smaller and more transient alterations were observed in BDNF protein levels, and these protein alterations did not alter levels of activated ERK. Study 3 investigated whether administration of BDNF attenuated the neuropatholoical and behavioral deficits that are associated with FP injury. BDNF attenuated the size of the cortical lesion by approximately 30% after a FP injury of moderate severity, but did not attenuate cognitive deficits. These studies support a role for BDNF in providing partial neuroprotection following FP injury.