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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.

Background: Platelet-neutrophil aggregates (PNAs) are fundamental mechanisms linking hemostasis and inflammatory processes. Elevated level of PNAs have been reported in inflammatory diseases and coronary artery diseases. However, studies on the correlation between PNAs formation and deep venous thrombosis (DVT) are not available. Methods: A total of 92 participants were involved in this study, including 32 cases with DVT and 60 cases without DVT. Blood samples coagulated by K2-EDTA or sodium citrate were prepared for blood cell count and blood smears. PNAs and platelet activation were measured using flow cytometry. The correlation between platelet activation level and PNAs level was analyzed by linear regression. Receiver operating characteristic (ROC) analysis was performed, assessing the prognostic performance of PNAs to predict potential risk of DVT occurrence. Results: PNAs was found in the blood smears of patients with DVT. Significant increased level of PNAs was identified in DVT group (medium 8.43%, interquartile range [IQR] 4.11%–15.69%), compared with that in control group (5.16%, IQR 2.40–9.60, p<0.01). The DVT group also showed a dramatic elevated level of total platelet activation (medium 16.06%, IQR 6.04–22.05) vs. control group (11.26%, IQR 5.54–19.99, p<0.05). The PNAs level was correlated with total platelet activation (r2=0.58, p<0.0001). A significantly high odds ratio (OR) of DVT occurrence was identified when the level of PNAs was higher than 7.4% (OR 3.60, 95% confidence interval [CI] 1.463–8.838, p<0.01). Conclusions: An elevated level of PNAs was associated with risk of DVT occurrence, which might be a suitable marker predicting DVT development. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]