Formation of Microparticles in the Injured Brain of Patients with Severe Isolated Traumatic Brain Injury

Abstract

The potential pathophysiological role of circulating microparticles (MPs) has been recognized in various conditions, such as cardiovascular and thrombotic diseases. Traumatic brain injury (TBI) has a complex pathophysiology that involves coagulopathy and inflammation. We investigated endothelial-, platelet-, and leukocyte-derived microparticles (EMPs, PMPs, and LMPs, respectively) in 16 patients with severe isolated TBI. Arterial and cerebrovenous samples were taken repeatedly, during 1-72 h after injury. Subpopulations of MPs, exposing tissue factor (TF) and P-selection, were also studied. MP counts in cerebrovenous samples, irrespective of cellular origin, were higher in TBI cases, compared to healthy controls (peak levels of EMPs were approximately 7 times higher, PMPs 1.4 times higher, and LMPs 2 times higher, respectively; p<0.001 for all). MP counts declined sharply from high levels shortly after the trauma toward slightly elevated levels 72 h later. EMPs and PMPs exposing TF, as well as PMPs exposing P-selection, showed a transcranial gradient with higher concentration in cerebrovenous, compared to arterial, samples. In contrast, LMPs exposing TF were higher in arterial samples, suggesting accumulation of LMPs in the brain. We conclude that the pattern of circulating MPs is altered after TBI. PMPs exposing P-selection and EMPs exposing TF seem to be generated in the injured brain, whereas LMPs exposing TF are accumulated. The pathophysiological significance of these changes in MP pattern in TBI should be further investigated. Including MPs exposing brain-specific antigens in the assessment of brain injury would give further information of origin and likely give additional information of the size of the injury, given that the MP phenotypes investigated in the present study are not brain-specific markers.

Dynamics of fibrinogen in acute phases of trauma

“…In animal models of brain trauma, brain-derived microparticles that expressed neuronal or glial cell markers were detected in the systemic circulation [31,32]. These microparticles were confirmed to express not only pro-coagulant phosphatidylserine but also tissue factor on their membranes [29,31,32].…”

“…2) [14][15][16][17]. These circulating pro-coagulants are known as damage-associated molecular patterns (DAMPs) [18][19][20][21][22][23][24][25][26] and microparticles [27][28][29][30][31][32] released from injured organs/tissues. Extracellular DNA and DNA-binding proteins are the principal DAMPs that comprise the pro-coagulants detected in severe trauma patients.…”

“…Various cell-derived microparticles have been detected during the acute phase of severe trauma [27][28][29][30][31][32]. Plateletderived microparticles are well-known pro-coagulants in the acute phase of trauma [27][28][29].…”

“…Plateletderived microparticles are well-known pro-coagulants in the acute phase of trauma [27][28][29]. Furthermore, leukocyte-, erythrocyte-, and endothelial cell-derived microparticles are also released into the systemic circulation in the acute phase of trauma (29,30).…”

“…Plateletderived microparticles are well-known pro-coagulants in the acute phase of trauma [27][28][29]. Furthermore, leukocyte-, erythrocyte-, and endothelial cell-derived microparticles are also released into the systemic circulation in the acute phase of trauma (29,30). In animal models of brain trauma, brain-derived microparticles that expressed neuronal or glial cell markers were detected in the systemic circulation [31,32].…”