Contribution of systemic factors in the pathophysiology of repeated blast-induced neurotrauma.
Blast-induced traumatic brain injury is complex and involves multiple factors including systemic pathophysiological factors in addition to direct brain injuries. We hypothesize that systemic activation of platelets/leukocytes plays a major role in the development and exacerbation of brain injury after blast exposure. A mouse model of repeated blast exposure that results in significant neuropathology, neurobehavioral changes and regional specific alterations in various biomolecules in the brain was used for the proposed study. Activation of platelets was evaluated by flow cytometry and serotonin content was analyzed by ELISA. Expression of myeloperoxidase was analyzed by Western blotting. Histopathology of the brain was used to assess blast-induced cerebral vasoconstriction. The data showed an increase in the activation of platelets at 4h after repeated blast exposures, indicating changes in platelet phenotype in blast neurotrauma. Platelet serotonin concentration showed a significant decrease at 4h after blast with a concurrent increase in the plasma serotonin levels, confirming the early onset of platelet activation after repeated blast exposures. Blood, plasma and brain myeloperoxidase enzyme activity and expression was increased in repeated blast exposed mice at multiple time points. Histopathological analysis of the brains of blast exposed mice showed constriction of blood vessels compared to the respective controls, a phenomenon similar to the reported cerebral vasoconstriction in blast affected victims. These results suggest that repeated blast exposure leads to acute activation of platelets/leukocytes which can augment the pathological effects of brain injury. Platelet/leukocyte targeted therapies can be evaluated as potential acute treatment strategies to mitigate blast-induced neurotrauma.
Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. m.valiyaveettil@us.army.mil
Manojkumar
M
Valiyaveettil
Yonas
Y
Alamneh
Ying
Y
Wang
Peethambaran
P
Arun
Samuel
S
Oguntayo
Yanling
Y
Wei
Joseph B
JB
Long
Madhusoodana P
MP
Nambiar
D000818:Animals; D001753:Blast Injuries / Q000378:metabolism* / Q000503:physiopathology; D001792:Blood Platelets / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D014661:Vasoconstriction
D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D012701:Serotonin; D009195:Peroxidase