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 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 &#xb1; 282 vs 1,636 &#xb1; 434 LEU/100 &#x3bc;m/minutes, P < .05). Mannitol also displayed lower tissue accumulation of leukocytes as compared with progesterone (5.7 &#xb1; 1.7 vs 15.2 &#xb1; .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.