Synergistic benefits of erythropoietin and simvastatin after traumatic brain injury.
Simvastatin and recombinant human erythropoietin (rhEpo) are implicated as potential therapeutic candidates for traumatic brain injury (TBI). Prominent effects of simvastatin include its anti-inflammatory, neurotrophic and neuroregenerative actions studied in various models of neuronal injury. On the other hand, rhEpo has been shown to promote cell survival mechanisms by producing anti-apoptotic and cell proliferative actions. Beneficial effects of rhEpo and statin monotherapies have been well studied. However, there are no reports showing combined use of rhEpo and statins after TBI. This investigation examined if combined efficacy of cell proliferative ability of rhEpo along with the neuroregenerative ability of simvastatin will render maximum recovery in a controlled cortical impact (CCI) mouse model of TBI. Results showed that compared to baseline TBI, rhEpo was more effective than simvastatin in promoting cell proliferation while simvastatin was more effective than rhEpo in restoring axonal damage following TBI. Combined treatment with simvastatin and rhEpo maximally restored axonal integrity while simultaneously inducing greater proliferation of newly formed cells resulting in better functional recovery after TBI than either alone. This is the first study showing the efficacy of erythropoietin-simvastatin combinational therapeutic approach in achieving greater structural and cognitive recovery after TBI.
Chauhan
Neelima B
NB
Jesse Brown VA Medical Center, University of Illinois, Chicago, USA. nchauhan@uic.edu
Gatto
Rodolfo
R
D000818:Animals; D000963:Antimetabolites; D001369:Axons / Q000187:drug effects / Q000473:pathology; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D001973:Bromodeoxyuridine; D049109:Cell Proliferation / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D004357:Drug Synergism; D004921:Erythropoietin / Q000627:therapeutic use*; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009416:Nerve Regeneration / Q000187:drug effects; D011994:Recombinant Proteins; D020127:Recovery of Function; D019821:Simvastatin / Q000627:therapeutic use*
D000963:Antimetabolites; D006454:Hemoglobins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011994:Recombinant Proteins; D004921:Erythropoietin; D019821:Simvastatin; D001973:Bromodeoxyuridine