Treatment with MG53 ameliorates traumatic brain injury-associated acute kidney injury.

Journal: The Journal Of Trauma And Acute Care Surgery
Published:
Abstract

Background: Multiorgan dysfunction (MOD) after traumatic brain injury (TBI) results in increased morbidity and mortality. There is emerging evidence demonstrating TBI-induced inflammatory responses; however, the mechanisms driving TBI-induced organ injury remains unknown and understudied. MG53, a cell membrane repair protein, has been shown to reduce brain lesion size following TBI. In this study, we aimed to establish a large animal model of post-TBI MOD, determine MG53's role in renal protection following TBI, and explore a mechanistic link between endothelial cell dysfunction and post-TBI MOD.

Methods: Female Yorkshire swine (n = 5/group) were subjected to controlled cortical impact TBI and randomized to receive (1) MG53 protein therapy or (2) normal saline (control). Biomarkers of acute kidney injury were compared between the groups. Kidneys were analyzed for histologic evidence of acute injury. Top-down proteomics were performed on swine plasma at various times post-TBI.

Results: Control animals had a significant increase in creatinine from baseline by 6 hours post-TBI (p = 0.007), which was attenuated in the MG53-treated animals (p = 0.089). Control animals had a significant increase in plasma NGAL from baseline starting at 4 hours from baseline (p = 0.014). Animals treated with MG53 had no change in serum NGAL from baseline (p = 0.163). Histologic analysis showed protection of proximal tubular epithelial cell damage in animals treated with MG53. Proteoform data showed differential expression of apolipoprotein 1, fibrinogen β, and osteocalcin.

Conclusions: Traumatic brain injury can induce distant organ damage, possibly through endothelial cell dysfunction, and treatment with a cell membrane repair protein (MG53) can protect against this injury.

Authors
Marjorie Liggett, Bowen Wang, Zaiba Dawood, Mengxue Zhang, Guang Jin, Jessie Ho, Meredith Taylor, Vincent White, Indira Pla, Aniel Sanchez, Michael Caldwell, Neil Kelleher, Baoling Liu, Daniel Couchenour, Aleezeh Shaikh, Yonggang Yao, Ki Park, Jianjie Ma, Hasan Alam