BACKGROUND: Recent epidemiologic evidence has identified beta-blockade as independently associated with improved survival in patients with isolated traumatic brain injury (TBI). Reduced sympathetic discharge and catecholamine release may improve circulation in the injured areas and influence delayed demise. The purpose of this study was to investigate the cerebral effect of beta-blockade in a murine TBI model using immunohistochemical and microPET analysis. METHODS: Balb/c mice underwent TBI as in a previously described model and were randomized to receive treatment with propranolol or placebo in a blinded fashion. Immunofluorescent images were obtained for vessel density (CD31), vessel perfusion (Ricinus communis agglutinin [RCA]-lectin), and cerebral hypoxia (hypoxyprobe-1) and compared by digital quantification. Perfusion measurements were acquired using positron emission tomography microPET scans with [64Cu]-pyruvaldehyde bis(N4-methylthiosemicarbazone) ([64Cu]-PTSM) and converted into standardized uptake values (SUV) for analysis. RESULTS: On immunohistochemical analysis, the normal mouse cerebral perfusion was a quantitated mean of 325 +/- 20, the cerebral perfusion after TBI and treatment with placebo was 113 +/- 25, and the cerebral perfusion after TBI treated with propranolol was 172 +/- 23. Immunohistochemical analysis demonstrated treatment with propranolol improved cerebral perfusion by 152% (p value <0.01) and reduced cerebral hypoxia by 24.2% (p value <0.01) compared with treatment with placebo. MicroPET imaging of the normal mouse brain after injection with placebo measured a SUV of 0.7075 +/- 0.02; the normal mouse brain after treatment with propranolol measured a SUV of 0.400 +/- 0.02. After TBI and treatment with placebo, the SUV reduced to 0.395 +/- 0.01; after treatment with propranolol the SUV measured 0.515 +/- 0.04. MicroPET imaging demonstrated propranolol improved cerebral perfusion after TBI to 130% of placebo (p value <0.01). CONCLUSION: Propranolol in vivo increased cerebral perfusion and decreased cerebral hypoxia. This research demonstrates beta-blockade may prevent additional brain damage after traumatic insult and should be the focus of future clinical trials.
BACKGROUND: Recent epidemiologic evidence has identified beta-blockade as independently associated with improved survival in patients with isolated traumatic brain injury (TBI). Reduced sympathetic discharge and catecholamine release may improve circulation in the injured areas and influence delayed demise. The purpose of this study was to investigate the cerebral effect of beta-blockade in a murine TBI model using immunohistochemical and microPET analysis. METHODS: Balb/c mice underwent TBI as in a previously described model and were randomized to receive treatment with propranolol or placebo in a blinded fashion. Immunofluorescent images were obtained for vessel density (CD31), vessel perfusion (Ricinus communis agglutinin [RCA]-lectin), and cerebral hypoxia (hypoxyprobe-1) and compared by digital quantification. Perfusion measurements were acquired using positron emission tomography microPET scans with [64Cu]-pyruvaldehyde bis(N4-methylthiosemicarbazone) ([64Cu]-PTSM) and converted into standardized uptake values (SUV) for analysis. RESULTS: On immunohistochemical analysis, the normal mouse cerebral perfusion was a quantitated mean of 325 +/- 20, the cerebral perfusion after TBI and treatment with placebo was 113 +/- 25, and the cerebral perfusion after TBI treated with propranolol was 172 +/- 23. Immunohistochemical analysis demonstrated treatment with propranolol improved cerebral perfusion by 152% (p value <0.01) and reduced cerebral hypoxia by 24.2% (p value <0.01) compared with treatment with placebo. MicroPET imaging of the normal mouse brain after injection with placebo measured a SUV of 0.7075 +/- 0.02; the normal mouse brain after treatment with propranolol measured a SUV of 0.400 +/- 0.02. After TBI and treatment with placebo, the SUV reduced to 0.395 +/- 0.01; after treatment with propranolol the SUV measured 0.515 +/- 0.04. MicroPET imaging demonstrated propranolol improved cerebral perfusion after TBI to 130% of placebo (p value <0.01). CONCLUSION:Propranolol in vivo increased cerebral perfusion and decreased cerebral hypoxia. This research demonstrates beta-blockade may prevent additional brain damage after traumatic insult and should be the focus of future clinical trials.
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: Neale S Mason; Brian J Lopresti; James Ruszkiewicz; Xinxin Dong; Sonali Joyce; George Leef; Malabika Sen; Abdus S Wahed; Chester A Mathis; Jennifer R Grandis; Sufi M Thomas Journal: Am J Nucl Med Mol Imaging Date: 2013-01-05
Authors: Yi Ping Zhang; Jun Cai; Lisa B E Shields; Naikui Liu; Xiao-Ming Xu; Christopher B Shields Journal: Transl Stroke Res Date: 2014-02-05 Impact factor: 6.829
Authors: Douglas Z Liou; Ara Ko; Oksana Volod; Galinos Barmparas; Megan Y Harada; Matthew J Martin; Ali Salim; Navpreet Dhillon; Gretchen M Thomsen; Eric J Ley Journal: Neurocrit Care Date: 2016-08 Impact factor: 3.210