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

American journal of surgery (2014-10-13)
Kenichiro Kumasaka, Joshua A Marks, Rachel Eisenstadt, Mohammad A Murcy, Davoud Samadi, Shengjie Li, Victoria Johnson, Kevin D Browne, Douglas H Smith, C William Schwab, Jose L Pascual
ABSTRACT

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. 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. 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. 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
D-Mannitol, ≥98%
Sigma-Aldrich
Progesterone, ≥99%
Supelco
Mannitol, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Progesterone, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
D-Mannitol, ACS reagent
Sigma-Aldrich
D-Mannitol, meets EP, FCC, USP testing specifications
Sigma-Aldrich
D-Mannitol, BioXtra, ≥98% (HPLC)
Sigma-Aldrich
D-Mannitol, suitable for plant cell culture
Mannitol, European Pharmacopoeia (EP) Reference Standard
Supelco
Progesterone, Pharmaceutical Secondary Standard; Certified Reference Material
Millipore
D-Mannitol, ACS reagent, suitable for microbiology, ≥99.0%
USP
Mannitol, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
D-Mannitol, BioUltra, ≥99.0% (sum of enantiomers, HPLC)
Supelco
Progesterone solution, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
Progesterone, γ-irradiated, BioXtra, suitable for cell culture
Sigma-Aldrich
Progesterone, meets USP testing specifications
Sigma-Aldrich
D-Mannitol, tested according to Ph. Eur.
USP
Progesterone, United States Pharmacopeia (USP) Reference Standard
Supelco
D-Mannitol, ≥99.9999% (metals basis), for boron determination
Supelco
Progesterone, VETRANAL®, analytical standard
Progesterone, European Pharmacopoeia (EP) Reference Standard