Induction of traumatic brain and spinal cord injury models in rat using a modified impactor device

Introduction: The use of standard rodent model, allows for the understanding of neuronal injury physiopathology and helping development of therapeutic strategies. Because of eliminating technical problems, we designed a modified impactor device with ability to induce different degrees according to kilodyne from very mild to very severe of spinal cord injury (SCI) and traumatic brain injury (TBI) models in rat. Methods: For standardization and determining of optimal performance of the device to induce varying injuries, 47 adult male Wistar rats were used, and 8 different forces were applied in spinal cord and brain tissues. Results: The hematoxylin and eosin and 2, 3, 5-triphenyltetrazolium chloride (TTC) results demonstrated that by increasing the level of forces, histological changes in the spinal cord and brain were significantly enhanced. Different injuries had significant effect on the Basso-Beattie-Brenham and elevated body swing test outcomes, and there were significant differences between groups in comparison with control group. Conclusion: Our results showed that the modified device could be valid to produce precise SCI and TBI models, goal to replicate SCI and TBI in humans as much as possible. However, it might be considered that aspects of SCI and TBI models are complicate and more examination is necessary. iD Induction of traumatic brain and spinal cord injury models in rat using a modified impactor device D ow nl oa de d fr om p pj . p hy ph a. ir at 1 0: 14 + 03 30 o n M on da y N ov em be r 4t h 20 19 229 | Physiol Pharmacol 22 (2018) 228-239 Ghorbani et al. tissue devastation (Gaetz, 2004; Cernak, 2005; Masel and DeWitt, 2010). This primary stage is followed by secondary phase of SCI characterizing with cellular and molecular dysfunctions (Thompson et al., 2005; Marklund et al., 2006; Bramlett and Dietrich, 2007). Among different techniques, contusion method using New York University (NYU), the Ohio State University (OSU) (Stokes, 1992) and the Infinite horizon (IH) devices (Lee et al., 2012) are widely applied for induction of SCI in rodents (Iwanami et al., 2005; Khuyagbaatar et al., 2015). The SCI producing by the NYU device results from dropping of a 10-g rod from different heights on exposed special part of the spinal cord (Gruner, 1992). In the primary version, NYU impactor device couldn’t record digital parameters, but in the ultimate version the device is able to control some mechanical parameters to create different injuries, however, as a disadvantage, duration of impact cannot be exactly controlled (Iwanami et al., 2005). The OSU or electromagnetic spinal cord injury device (ESCID) can produce a range of spinal cord injuries by applying different displacement onto exposed spinal cord (Noyes, 1987; Stokes et al., 1992). The device improved in 2000 to investigate in SCI model in mouse (Jakeman et al., 2000) and cervical spine injury in the rat (Pearse et al., 2005). There is merely a limitation of the OSU impactor that discerning the zero point for the impactor sometimes is difficult (Cheriyan et al., 2014). Finally, the IH device is made for crating different severity of injuries using a force-controlled impact on the spinal cord tissue and graded contusion injury will generate by entering a predetermined force in specific software which calibrated according to mild (100kdyn), moderate (150kdyn) and sever (200kdyn) forces at different segments of spinal cord in the rat (Scheff et al., 2003). In this device, an apparent limitation revealed by some researchers relating to spinal cord holder which finally caused to create a custom type of clamping instrument to cope with that technical problem (Streijger et al., 2013). Considering, TBI models divided into four specific models as follow; fluid percussion injury (FPI) (Dixon et al., 1987), weight-drop impact injury (Marmarou et al., 1994), blast injury (Leung et al., 2008) and controlled cortical impactor (Lighthall, 1988; Dixon et al., 1991). The FPI model creates by a fluid rapid injection into the brain space following craniotomy and the different degrees of injury relies on the strength of the pressure (McIntosh et al., 1989). As a beneficial change in next version, FPI model improved by providing a microprocessor-controlled and contemplating adjustable biomechanical parameters (Kabadi et al., 2010). Weight-drop model, a weight releases straight onto the exposed dura matter from a desired height to induce a cortical injury (Feeney et al., 1981). Overtly, one remarkable disadvantage of the weight-drop models relates to high variation in creating different severities of injury; however, because of several reasons, including economic efficiency, easy to accomplish and similar TBI method in human, it should be considered as an applicable and common approach in experimental condition (Xiong et al., 2013). Blast brain injury causes by blast which commonly happens in various military personnel (Long et al., 2009). The controlled cortical impact (CCI), injury model induces by an air or electromagnetic device (Xiong et al., 2013). The advantage of CCI compared to other models is adjustable mechanical parameters, such as velocity, time and depth (Wang and Ma, 2010), and with this way, severity of injury can be appropriate for specific experiments ( Goodman et al., 1994). Therefore, all of these devices were generally employed and developed for traumatic brain and spinal cord injuries, separately, and each one has its specific feature of injury. In this study a modified device is produced inducing either SCI or TBI models in rats. To gain several targets effectively, we have designed a device with usability in the spinal cord and brain trauma models that could create more wide range of injury with slight variation and low heterogeneity in order to help researcher for understanding precise pathophysiological