Project Grant R01NS138333

This federal Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program provides $591,304 to the University of Louisville to investigate the role of the integrated stress response (ISR) kinase HRI in mediating secondary injury and neuroinflammation after traumatic spinal cord injury (SCI).

The key objectives are to: 1) Test the cell-autonomous contributions of HRI to oligodendrocyte death after SCI, 2) Define the role of HRI in regulating SCI-associated neuroinflammation, and 3) Examine whether pharmacological inhibition of HRI can improve SCI outcomes. The research will use mouse models with cell-specific HRI deletions and a CNS-permeable HRI inhibitor to understand the mechanistic links between HRI activation, oligodendrocyte death, and cytotoxic neuroinflammation following contusive SCI. The goal is to identify HRI as a potential therapeutic target for promoting neuroprotection and reducing secondary injury after traumatic CNS damage.