In vivo leukocyte-mediated brain microcirculatory inflammation: a comparison of osmotherapies and progesterone in severe traumatic brain injury

Abstract Background Mannitol, hypertonic saline, and progesterone may blunt leukocyte recruitment after traumatic brain injury (TBI). We hypothesized that progesterone reduces pericontusional recruitment of leukocytes to a greater extent than either osmotherapy a day after TBI. Methods CD1 mice unde...

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Bibliographic Details
Published in:The American journal of surgery 2014-12, Vol.208 (6), p.961-968
Main Authors: Kumasaka, Kenichiro, M.D, Marks, Joshua A., M.D, Eisenstadt, Rachel, B.A, Murcy, Mohammad A., M.D, Samadi, Davoud, M.D, Li, Shengjie, M.D, Johnson, Victoria, M.D, Browne, Kevin D., B.A, Smith, Douglas H., M.D, Schwab, C. William, M.D, Pascual, Jose L., M.D., Ph.D
Format: Article
Language:English
Subjects:
Animals
Brain damage
Brain Edema - drug therapy
Brain Edema - pathology
Brain Injuries - drug therapy
Brain Injuries - pathology
Cytotoxicity
Disease Models, Animal
Immunohistochemistry
Intravital microscopy
Leukocytes
Leukocytes - drug effects
Male
Mannitol - pharmacology
Mice
Microcirculation - drug effects
Mortality
Neuroinflammation
Osmotherapy
Patients
Permeability
Polymorphonuclear neutrophil
Progesterone
Progesterone - pharmacology
Rodents
Saline Solution, Hypertonic - pharmacology
Surgery
Traumatic brain injury
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Summary:Abstract Background Mannitol, hypertonic saline, and progesterone may blunt leukocyte recruitment after traumatic brain injury (TBI). We hypothesized that progesterone reduces pericontusional recruitment of leukocytes to a greater extent than either osmotherapy a day after TBI. Methods CD1 mice underwent controlled cortical impact and were treated with osmotherapy (mannitol and hypertonic saline) or progesterone. Thirty-two hours after TBI, live pial microscopy was used to evaluate leukocyte–endothelial interactions and immunohistochemistry was used for the detection of pericontusional tissue polymorphonuclear neutrophils. Neurologic recovery was assessed before sacrifice. Results Mannitol resulted in the lowest in vivo leukocyte recruitment compared with progesterone (795 ± 282 vs 1,636 ± 434 LEU/100 μm/minutes, P < .05). Mannitol also displayed lower tissue accumulation of leukocytes as compared with progesterone (5.7 ± 1.7 vs 15.2 ± .1 LEU/mm2 , P = .03). However, progesterone resulted in better neurologic recovery than either osmotherapy. Conclusions Leukocyte recruitment to injured brain is lowest with mannitol administration. How different agents alter progression of secondary brain injury will require further evaluation in humans.
ISSN:0002-9610
1879-1883
DOI:10.1016/j.amjsurg.2014.08.004