BACKGROUND: In vivo models of traumatic brain injury (TBI) demonstrate increased cerebral perfusion, decreased cerebral hypoxia, reduced cerebral edema, and improved neurologic recovery with propranolol administration. The purpose of this study was to determine the effect of different propranolol doses and timing on cerebral perfusion in a murine TBI model. METHODS: Fifteen minutes after TBI, three groups of mice (four mice per group) were randomized to receive intravenous injections of placebo, 4 mg/kg propranolol, or 1 mg/kg propranolol. Two delayed treatment groups were randomized to receive placebo or 4 mg/kg propranolol 60 minutes after TBI. Cerebral perfusion was then imaged by micropositron emission tomography. RESULTS: With placebo injection 15 minutes after TBI, the standard uptake value (SUV) mean was 0.395 +/- 0.01; with 4 mg/kg propranolol, the SUV mean was 0.515 +/- 0.04; and with 1 mg/kg propranolol, the SUV mean was 0.46 +/- 0.01. Animals receiving 4 mg/kg propranolol demonstrated significant improvement (p < 0.01) in cerebral perfusion compared with placebo and compared with 1 mg/kg propranolol. With placebo injection at 60 minutes after TBI, the SUV mean was 0.26 +/- 0.03; and with 4 mg/kg propranolol, the SUV mean was 0.43 +/- 0.02. After 60 minutes, animals receiving 4 mg/kg propranolol demonstrated significant improvement (p < 0.01) in cerebral perfusion compared with placebo. CONCLUSION: In a murine model of TBI, higher doses of propranolol were preferable to lower doses and both early and late propranolol administration improved cerebral perfusion. Potential mechanisms and therapeutic potential require further research.
BACKGROUND: In vivo models of traumatic brain injury (TBI) demonstrate increased cerebral perfusion, decreased cerebral hypoxia, reduced cerebral edema, and improved neurologic recovery with propranolol administration. The purpose of this study was to determine the effect of different propranolol doses and timing on cerebral perfusion in a murine TBI model. METHODS: Fifteen minutes after TBI, three groups of mice (four mice per group) were randomized to receive intravenous injections of placebo, 4 mg/kg propranolol, or 1 mg/kg propranolol. Two delayed treatment groups were randomized to receive placebo or 4 mg/kg propranolol 60 minutes after TBI. Cerebral perfusion was then imaged by micropositron emission tomography. RESULTS: With placebo injection 15 minutes after TBI, the standard uptake value (SUV) mean was 0.395 +/- 0.01; with 4 mg/kg propranolol, the SUV mean was 0.515 +/- 0.04; and with 1 mg/kg propranolol, the SUV mean was 0.46 +/- 0.01. Animals receiving 4 mg/kg propranolol demonstrated significant improvement (p < 0.01) in cerebral perfusion compared with placebo and compared with 1 mg/kg propranolol. With placebo injection at 60 minutes after TBI, the SUV mean was 0.26 +/- 0.03; and with 4 mg/kg propranolol, the SUV mean was 0.43 +/- 0.02. After 60 minutes, animals receiving 4 mg/kg propranolol demonstrated significant improvement (p < 0.01) in cerebral perfusion compared with placebo. CONCLUSION: In a murine model of TBI, higher doses of propranolol were preferable to lower doses and both early and late propranolol administration improved cerebral perfusion. Potential mechanisms and therapeutic potential require further research.
Authors: Aziz S Alali; Kaushik Mukherjee; Victoria A McCredie; Eyal Golan; Prakesh S Shah; James M Bardes; Susan E Hamblin; Elliott R Haut; James C Jackson; Kosar Khwaja; Nimitt J Patel; Satish R Raj; Laura D Wilson; Avery B Nathens; Mayur B Patel Journal: Ann Surg Date: 2017-12 Impact factor: 12.969
Authors: Daniel J Kota; Karthik S Prabhakara; Alexandra J van Brummen; Supinder Bedi; Hasen Xue; Bryan DiCarlo; Charles S Cox; Scott D Olson Journal: Stem Cells Transl Med Date: 2015-11-19 Impact factor: 6.940
Authors: Mayur B Patel; John W McKenna; JoAnn M Alvarez; Ayaka Sugiura; Judith M Jenkins; Oscar D Guillamondegui; Pratik P Pandharipande Journal: Trials Date: 2012-09-26 Impact factor: 2.279
Authors: Alfonso J Lopez; Mohamed ElSaadani; Christina L Jacovides; Anastasia Georges; Matthew C Culkin; Syed Ahmed; Monisha A Kumar; Lewis J Kaplan; Douglas H Smith; Jose L Pascual Journal: J Trauma Acute Care Surg Date: 2022-01-18 Impact factor: 3.697