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Am J Surg. 2014 Dec;208(6):961-8; discussion 967-8. doi: 10.1016/j.amjsurg.2014.08.004. Epub 2014 Sep 22.

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

Author information

1
Department of Surgery, Division of Traumatology, Surgical Critical Care and Emergency Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
2
Department of Neurosurgery, Center for Brain Injury and Repair, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
3
Department of Surgery, Division of Traumatology, Surgical Critical Care and Emergency Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: jose.pascual@uphs.upenn.edu.

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/mm(2), 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.

KEYWORDS:

Intravital microscopy; Neuroinflammation; Osmotherapy; Polymorphonuclear neutrophil; Progesterone; Traumatic brain injury

PMID:
25305798
PMCID:
PMC5448132
DOI:
10.1016/j.amjsurg.2014.08.004
[Indexed for MEDLINE]
Free PMC Article

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