C6: The impact of traumatic brain injury (TBI) and acute psychological stress (AS) on neuronal integrity and nerve regeneration
PI: B. Knöll
Data derived from the current CRC project showed a role of the transcription factors SRF and ATF3 in traumatic brain injury (TBI) and peripheral nerve injury including modulation of gene expression, neuronal regeneration and behavioral recovery. In the next funding period we extend on this by analysing the role of these gene regulators in mice exposed to a combination of physical and psychological trauma. For this, we combine the weight-drop TBI model with an established acute stress (AS) model in mice (so-called immobilization stress). With these two models at hand, consequences of a previous AS exposure on subsequent physical brain trauma will be investigated. By reversing the sequence, we analyse the impact of an initial TBI event on subsequent acute stress responsiveness (e.g. locomotor activity, corticosterone release). So far, the connection of AS and TBI has been poorly studied. Thus, we provide first detailed insight on this psychological and physical trauma interplay. SRF and ATF3 have previously been connected to AS and brain injury responses. We employ Srf and Atf3 mutagenesis in mice to identify these factors as potential molecular determinants modulating the acute stress-brain trauma connection. In the second project part we include a translational approach aiming at enhancing the regeneration potential of neurons after injury. Here, we use self-assembling peptides (SAPs) whose polymerization results in nanofibre networks. In completed work we identified single nanofibres enhancing adhesion and nerve fibre growth of mouse primary neurons. These SAPs also stimulated peripheral nerve regeneration in mice. In the new project, we analyse the regeneration stimulating potential of a “second nanofibre generation”. This new biomaterial was functionalized with active growth factor domains (of e.g. GDNF) or adhesion molecules (laminin). We employ primary neurons and the established mouse TBI model to test their regeneration promoting potential. Thus, with this translational approach we hope to identify new biomaterials alleviating the impact of brain injury.