title: Intravenous administration of Honokiol provides neuroprotection and improves functional recovery after traumatic brain injury through cell cycle inhibition.
abstract: Recently, increasing evidence has shown that cell cycle activation is a key factor of neuronal death and neurological dysfunction after traumatic brain injury (TBI). This study aims to investigate the effects of Honokiol, a cell cycle inhibitor, on attenuating the neuronal damage and facilitating functional recovery after TBI in rats, in an attempt to unveil its underlying molecular mechanisms in TBI. This study suggested that delayed intravenous administration of Honokiol could effectively ameliorate TBI-induced sensorimotor and cognitive dysfunctions. Meanwhile, Honokiol treatment could also reduce the lesion volume and increase the neuronal survival in the cortex and hippocampus. The neuronal degeneration and apoptosis in the cortex and hippocampus were further significantly attenuated by Honokiol treatment. In addition, the expression of cell cycle-related proteins, including cyclin D1, CDK4, pRb and E2F1, was significantly increased and endogenous cell cycle inhibitor p27 was markedly decreased at different time points after TBI. And these changes were significantly reversed by post-injury Honokiol treatment. Furthermore, the expression of some of the key cell cycle proteins such as cyclin D1 and E2F1 and the associated apoptosis in neurons were both remarkably attenuated by Honokiol treatment. These results show that delayed intravenous administration of Honokiol could effectively improve the functional recovery and attenuate the neuronal cell death, which is probably, at least in part, attributed to its role as a cell cycle inhibitior. This might give clues to developing attractive therapies for future clinical trials.
authors: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing 400016, China.
authors: Haiquan
authors: H
authors: Wang
authors: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing 400016, China.
authors: Zhengbu
authors: Z
authors: Liao
authors: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing 400016, China.
authors: Xiaochuan
authors: X
authors: Sun
authors: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing 400016, China.
authors: Quanhong
authors: Q
authors: Shi
authors: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing 400016, China.
authors: Gang
authors: G
authors: Huo
authors: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing 400016, China.
authors: Yanfeng
authors: Y
authors: Xie
authors: Laboratory of Medical Molecular Biology, Medical College of Qinghai University, No.16 Kunlun Road, Xining 810000, Qinghai Province, China; Department of Cardiology, Medical College of Qinghai University, No.16 Kunlun Road, Xining 810000, Qinghai Province, China.
authors: Xiaolan
authors: X
authors: Tang
authors: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing 400016, China.
authors: Xinggang
authors: X
authors: Zhi
authors: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing 400016, China. Electronic address: zhaohua_tang@yahoo.com.
authors: Zhaohua
authors: Z
authors: Tang
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D001713:Biphenyl Compounds; D017705:Lignans; D018696:Neuroprotective Agents; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
keywords: Apoptosis; Cell cycle; Honokiol; Neuron; Neuroprotection; Traumatic brain injury