Two different pathways that lead to brain cell death are depicted in Figure 6, showing how calpain and caspase proteases may break down salmonid brain cellular proteins during both acute necrosis and delayed apoptosis phases of salmon head injury, respectively. Therefore, aII-spectrin was degraded by these two proteases, producing SBDPs as possible spillway force-mediated salmon brain injury biomarkers. Based on this study, there appears to be basal levels of SBDPs expressed in salmon brain tissues,PCI-27483 which may indicate a normal turnover of neuronal cells experienced during juvenile growth. Indeed, Zupanc reviews the capability of teleost brain tissues to display continuous neurogenesis postembryonically and into adulthood. Soutschek and Zupanc describe the neuronal turnover process as apoptotic regulation, but increased apoptosis is also seen in response to injury and removal of injured or affected cells. Although the difference in hydraulic force is orders of magnitude lower than passage through the spillway structures, it is possible that the bypassed fish used as a field control experienced some mild injury, and may account for the presence of SBDPs. However the presence of SBDPs in the control fish lends support to the neurogenesis hypothesis. The increase in SBDP120 appears to correlate with observations of head injury and could be used as a potential biomarker for subacute brain damage induced by migration passage. These results have increased significance following the recent Biological Opinion for the Federal Columbia River Power System for cooperating agencies to develop configuration and operations plans that detail overall survival improvements for in-river migrating fish. Although currently there is no threshold head injury biomarker expression level known that would indicate an outcome such as recovery, impaired health, or delayed mortality, the results can be compared among passage types to determine optimal passage trajectories, and are an improvement over current assessments that involve visible injury assessment for hundreds of fish per passage type. Non-lethal sampling is a preferred alternative to sampling brain tissue, and cerebral spinal fluid is the biofluid used for human biomarker analysis. However, CSF is not a viable alternative for juvenile fish that range in total size from 80– 140 mm. Blood samples may be a preferable biofluid for salmon brain injury biomarker monitoring. We are working to get salmon specific antibodies to enable the detection of the biomarker in blood. In addition,Tenapanor future work to assess degree of injury in relation to specific outcomes are underway and will include temporal studies under defined, laboratory simulations to determine more specific biomarker metrics for longer-term prognosis of fish outcome. Postnatal vessel formation, known as angiogenesis, was attributed to the migration and proliferation of preexisting mature endothelial cells. Recent studies demonstrated that circulating bone marrow-derived endothelial progenitor cells contribute to adult blood vessel formation, a process characterized as vasculogenesis. Endothelial progenitor cells play a major role in repair processes after myocardial infarction and wound healing. However, in vivo and in vitro studies revealed that endothelial progenitor cells from patients with type 1 and type 2 diabetes were impaired in number and function.