Traumatic brain injury (TBI) affects over 3 million individuals every year in the U.S. There is growing appreciation that TBI can produce systemic modifications, which are in part propagated through blood–brain barrier (BBB) dysfunction and blood–brain cell interactions. As such, platelets and leukocytes contribute to mechanisms of thromboinflammation after TBI. While these mechanisms have been investigated in experimental models of contusion brain injury, less is known regarding acute alterations following mild closed head injury. To investigate the role of platelet dynamics and bioenergetics after TBI, we employed two distinct, well-established models of TBI in mice: the controlled cortical impact (CCI) model of contusion brain injury and the closed head injury (CHI) model of mild diffuse brain injury. Hematology parameters, platelet-neutrophil aggregation, and platelet respirometry were assessed acutely after injury. CCI resulted in an early drop in blood leukocyte counts, while CHI increased blood leukocyte counts early after injury. Platelet-neutrophil aggregation was altered acutely after CCI compared to sham. Furthermore, platelet bioenergetic coupling efficiency was transiently reduced at 6 h and increased at 24 h post-CCI. After CHI, oxidative phosphorylation in intact platelets was reduced at 6 h and increased at 24 h compared to sham. Taken together, these data demonstrate that brain trauma initiates alterations in platelet-leukocyte dynamics and platelet metabolism, which may be time- and injury-dependent, providing evidence that platelets carry a peripheral signature of brain injury. The unique trend of platelet bioenergetics after two distinct types of TBI suggests the potential for utilization in prognosis.
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This research was funded by a VA Merit Award 1I01BX003405-01A1 (to P.G.S.), a VA Merit Award (to S.W.W.), and a Career Development Award, Number IK2 BX004618-01A1 (to W.B.H) from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Program. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. The work was also supported by NIH R01 NS112693-01A1 (to P.G.S.), NIH R21 NS114771-01A1 (to K.E.S.), NIH grants HL56652, HL138179, and HL150818 (to S.W.W.), the Kentucky Spinal Cord and Head Injury Research Trust (KSCHIRT) Grant 14-13A and 15-14A, and the American Heart Association grant AHA16GRNT31310020 (to Q.J.W.).
The data presented in this study are available on request from the corresponding author.
Hubbard, William Brad; Banerjee, Meenakshi; Vekaria, Hemendra J.; Prakhya, Kanakanagavalli Shravani; Joshi, Smita; Wang, Qingjun; Saatman, Kathryn E.; Whiteheart, Sidney W.; and Sullivan, Patrick G., "Differential Leukocyte and Platelet Profiles in Distinct Models of Traumatic Brain Injury" (2021). Spinal Cord and Brain Injury Research Center Faculty Publications. 37.