Federal Project Grant Award Summary

The National Institute of Neurological Disorders and Stroke (NINDS) awarded the University of Texas Medical Branch at Galveston a $161,500 Project Grant, effective June 8, 2026, through May 31, 2028, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853). The award supports the development of an inducible mouse model to investigate the role of Z-DNA binding protein 1 (ZBP1) in neuroinflammation associated with traumatic brain injury (TBI). The primary deliverable is a genetically engineered mouse model in which expression of a ZBP1 variant lacking nucleic acid-binding domains can be controlled, enabling direct testing of the proposed neuronal mitochondrial DNA-ZBP1 axis as a mechanism sustaining microglial activation across acute and chronic phases of TBI.

This research addresses a significant gap in understanding how microglial activation persists in TBI, particularly in mild cases where limited cell death or damage-associated molecular pattern (DAMP) release occurs. The project builds on preliminary findings suggesting that neuronal mitochondrial DNA (mtDNA), released via extracellular vesicles following TBI, activates microglia through ZBP1 binding and establishes a positive feedback loop perpetuating neuroinflammation. The mouse model will serve as a critical tool for validating this mechanism and potentially informing therapeutic strategies targeting the mtDNA-ZBP1 pathway to mitigate secondary neuronal injury in TBI patients.