Characterization of a New Rat Model of Experimental Combined Neurotrauma

Abstract

Traumatic brain injury (TBI) is present in two-thirds of patients with multiple injuries and in one-third combined with injuries of the extremities. Studies on interactive effects between central and peripheral injuries are scarce due to the absence of clinically relevant models. To meet the demand for "more-hit" models, an experimental model of combined neurotrauma (CNT) incorporating a standardized TBI via lateral fluid percussion (LFP) together with a peripheral bone fracture, i.e., tibia fracture, is introduced. Sprague-Dawley rats were randomized to four experimental groups: controls (n = 10), animals with TBI (n = 30), animals with tibia fracture (n = 30), and animals with CNT (n = 30). Morphological aspects of brain and bone injury were analyzed via standard histopathological procedures and x-ray. Trauma-induced neuromotor dysfunction was assessed using a standardized neuroscore. For interactive effects between injuries, we studied the extent and temporal pattern of circulating interleukin 6 (IL-6) levels via immunoassay and callus formation at fracture sites by means of microradiography. LFP produced an ipsilateral lesion with cortical contusion, hemorrhage, mass shift, and neuronal cell loss (adjacent cortex and hippocampus CA-2/-3), along with contralateral neuromotor dysfunction. X-rays confirmed complete fractures in the middle of the bone shaft. The type of injury (P < 0.001) and time (P = 0.022) were significantly associated with increased IL-6 levels. CNT produced the highest IL-6 plasma levels with a maximum peak at 6 h after trauma (P < 0.001). Similarly, callus formation at fracture sites in CNT was significantly increased versus fracture only (P < 0,01). The CNT model mimics a variety of clinically relevant features known from human multiple injury, including TBI, and offers novel approaches for investigation of interactive mechanisms and therapeutic approaches.

Neuropsychology and clinical neuroscience of persistent post-concussive syndrome

“…and all seem to relate to severity on some continuum (Anderson et al, 2003;Vorst et al, 2007). Taken together, in well controlled animal models there is a continuum associated with severity of impact injury supporting the contention that injury is on a continuum (Gurkoff et al, 2006;Igarashi et al, 2007;Kharatishvili et al, 2006;Maegele et al, 2005;Ucar et al, 2006). Understanding this continuum means that at the mildest level of brain perturbation there may, in fact, be no lasting effect.…”

Tibial Fracture Exacerbates Traumatic Brain Injury Outcomes and Neuroinflammation in a Novel Mouse Model of Multitrauma

“…6,7 Although TBI patients often experience concurrent bone fractures, most pre-clinical studies have utilized independent 'single-hit' injury models that do not reproduce the pathophysiologic complexities of multitrauma. 3,4,8,9 This has recently been recognized as a potential shortfall in the preclinical TBI field that may contribute to the failures in translating preclinical findings to the clinical setting. 7 Of particular relevance is bone fracture, which is known to induce a complex post-fracture healing process that involves an extensive inflammatory response in which immune cells proliferate and infiltrate the fracture site and secrete a range of pro-inflammatory cytokines into the circulation including interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6.…”

Effects of Palmitoylethanolamide on Signaling Pathways Implicated in the Development of Spinal Cord Injury

“…Moreover, PEA treatment significantly ameliorated the recovery of motor limb function. Together, the results indicate that PEA reduces inflammation and tissue injury associated with SCI and suggest a regulatory role for endogenous PPAR-␣ signaling in the inflammatory response associated with spinal cord trauma.Spinal cord injury (SCI) is a highly debilitating pathology (Maegele et al, 2005). Although innovative medical care has improved patient outcome, advances in pharmacotherapy for the purpose of limiting neuronal injury and promoting regeneration have been limited.…”

“…Spinal cord injury (SCI) is a highly debilitating pathology (Maegele et al, 2005). Although innovative medical care has improved patient outcome, advances in pharmacotherapy for the purpose of limiting neuronal injury and promoting regeneration have been limited.…”