Protection of FK506 against neuronal apoptosis and axonal injury following experimental diffuse axonal injury.
Diffuse axonal injury (DAI) is the most common and significant pathological features of traumatic brain injury (TBI). However, there are still no effective drugs to combat the formation and progression of DAI in affected individuals. FK506, also known as tacrolimus, is an immunosuppressive drug, which is widely used in transplantation medicine for the reduction of allograft rejection. Previous studies have identified that FK506 may play an important role in the nerve protective effect of the central nervous system. In the present study, apoptosis of neuronal cells was observed following the induction of experimental DAI. The results demonstrated that it was closely related with the upregulation of death‑associated protein kinase 1 (DAPK1). It was hypothesized that FK506 may inhibit the activity of DAPK1 by inhibiting calcineurin activity, which may be primarily involved in anti‑apoptosis following DAI induction. Through researching the expression of nerve regeneration associated proteins (NF‑H and GAP‑43) following DAI, the present study provides novel data to suggest that FK506 promotes axon formation and nerve regeneration following experimental DAI. Therefore, FK506 may be a potent therapeutic for inhibiting nerve injury, as well as promoting the nerve regeneration following DAI.
Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Ting-Qin
TQ
Huang
Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Jin-Ning
JN
Song
Department of Neurosurgery, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China.
Feng-Wei
FW
Zheng
Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Hong-Gang
HG
Pang
Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Yong-Lin
YL
Zhao
Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Hua
H
Gu
Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Jun-Jie
JJ
Zhao
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D001933:Brain Stem / Q000187:drug effects / Q000473:pathology; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000473:pathology; D019703:Calcineurin / Q000187:drug effects; D064550:Death-Associated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020833:Diffuse Axonal Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019922:GAP-43 Protein / Q000378:metabolism; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects; D016900:Neurofilament Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000494:pharmacology*; D015854:Up-Regulation
D019922:GAP-43 Protein; D016900:Neurofilament Proteins; C051774:neurofilament protein H; D064550:Death-Associated Protein Kinases; D019703:Calcineurin; D016559:Tacrolimus