Kenichiro Kumasaka1, Joshua A Marks1, Rachel Eisenstadt1, Mohammad A Murcy1, Davoud Samadi1, Shengjie Li1, Victoria Johnson2, Kevin D Browne2, Douglas H Smith2, C William Schwab1, Jose L Pascual3. 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.
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:CD1mice 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.
Authors: José L Pascual; Lorenzo E Ferri; Andrew J E Seely; Giuseppina Campisi; Prosanto Chaudhury; Betty Giannias; David C Evans; Tarek Razek; René P Michel; Nicolas V Christou Journal: Ann Surg Date: 2002-11 Impact factor: 12.969
Authors: Shengjie Li; Rachel Eisenstadt; Kenichiro Kumasaka; Victoria E Johnson; Joshua Marks; Katsuhiro Nagata; Kevin D Browne; Douglas H Smith; Jose L Pascual Journal: J Trauma Acute Care Surg Date: 2016-03 Impact factor: 3.313
Authors: Katsuhiro Nagata; Kevin D Browne; Yujin Suto; Kenichiro Kumasaka; John Cognetti; Victoria E Johnson; Joshua Marks; Douglas H Smith; Jose L Pascual Journal: J Trauma Acute Care Surg Date: 2017-09 Impact factor: 3.697
Authors: Yujin Suto; Katsuhiro Nagata; Syed M Ahmed; Christina Jacovides; Kevin D Browne; John Cognetti; Maura T Weber; Victoria E Johnson; Ryan Leone; Lewis J Kaplan; Douglas H Smith; Jose L Pascual Journal: J Trauma Acute Care Surg Date: 2018-08 Impact factor: 3.697
Authors: Katsuhiro Nagata; Yujin Suto; John Cognetti; Kevin D Browne; Kenichiro Kumasaka; Victoria E Johnson; Lewis Kaplan; Joshua Marks; Douglas H Smith; Jose L Pascual Journal: J Trauma Acute Care Surg Date: 2018-05 Impact factor: 3.697