Tahereh Ghadiri1, Mohammad Sharifzadeh2, Fariba Khodagholi3, Sayed Mostafa Modarres Mousavi4, Gholamreza Hassanzadeh5, Mohammad-Reza Zarrindast5, Ali Gorji6. 1. School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Shefa Neuroscience Research Center, Tehran, Iran. 2. School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Faculty of Pharmacy, Department of Toxicology, Tehran University of Medical Sciences, Tehran, Iran. 3. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 4. Shefa Neuroscience Research Center, Tehran, Iran. 5. School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. 6. Shefa Neuroscience Research Center, Tehran, Iran; Institute of Physiology I, Department of Neurosurgery, Epilepsy Research Center, Münster University, Germany; Institute of Physiology I, Department of Neurology, Epilepsy Research Center, Münster University, Germany. Electronic address: gorjial@uni-muenster.de.
Abstract
BACKGROUND: Due to the marked heterogeneity of human traumatic brain injury (TBI), none of the available animal model can reproduce the entire spectrum of TBI, especially mild focal TBI. This study was designed to develop a modified TBI weight drop model for induction of focal mild cerebral injury. NEW METHOD: A stereotaxic coupled weight drop device was designed. Principle arm of device carries up to 500g weights which their force was conveyed to animal skull through a thin nail like metal tip. To determine the optimal configuration of the device to induce mild TBI, six different trials were designed. The optimal configuration of the instrument was used for evaluation of behavioral, histopathological and molecular changes of mild TBI. RESULTS: Neurologic and motor coordination deficits observed sharply within 24h post injury period. Histological studies revealed a remarkable increase in the number of dark neurons in trauma site. TBI increased the expression of apoptotic proteins, Bax, BCl2 and cleaved caspase-3 in the hippocampus. COMPARISON WITH EXISTING METHODS: Our designed TBI device is capable to produce variable severity of TBI from mild to severe. The main advantage of the new TBI model is induction of mild local unilateral brain injury instead of traumatization of the whole brain. This model does not require craniotomy for induction of brain injury. CONCLUSION: This novel animal TBI model mimics human mild focal brain injury. This model is suitable for evaluation of pathophysiology as well as screening of new therapies for mild TBI.
BACKGROUND: Due to the marked heterogeneity of humantraumatic brain injury (TBI), none of the available animal model can reproduce the entire spectrum of TBI, especially mild focal TBI. This study was designed to develop a modified TBI weight drop model for induction of focal mild cerebral injury. NEW METHOD: A stereotaxic coupled weight drop device was designed. Principle arm of device carries up to 500g weights which their force was conveyed to animal skull through a thin nail like metal tip. To determine the optimal configuration of the device to induce mild TBI, six different trials were designed. The optimal configuration of the instrument was used for evaluation of behavioral, histopathological and molecular changes of mild TBI. RESULTS: Neurologic and motor coordination deficits observed sharply within 24h post injury period. Histological studies revealed a remarkable increase in the number of dark neurons in trauma site. TBI increased the expression of apoptotic proteins, Bax, BCl2 and cleaved caspase-3 in the hippocampus. COMPARISON WITH EXISTING METHODS: Our designed TBI device is capable to produce variable severity of TBI from mild to severe. The main advantage of the new TBI model is induction of mild local unilateral brain injury instead of traumatization of the whole brain. This model does not require craniotomy for induction of brain injury. CONCLUSION: This novel animal TBI model mimics human mild focal brain injury. This model is suitable for evaluation of pathophysiology as well as screening of new therapies for mild TBI.
Authors: Juan J Herrera; Kurt Bockhorst; Shakuntala Kondraganti; Laura Stertz; João Quevedo; Ponnada A Narayana Journal: J Neurotrauma Date: 2016-06-20 Impact factor: 5.269