A mouse model of acute ischemic spinal cord injury

Abstract

Mice models of spinal cord injury (SCI) should improve our knowledge of the mechanisms of injury and repair of the nervous tissue. They represent a powerful tool for the development of therapeutic strategies in the fields of pharmacological, cellular, and genetic approaches of neurotrauma. We demonstrate here that the photochemical graded ischemic spinal cord injury model, described in rats, can be successfully adapted in mice, in a reliable and reproducible manner. Following the intravenous injection of Rose Bengal, the translucent dorsal surface of the T9 vertebral laminae of C57BL/6 female mice was irradiated with a 560-nm wavelength-light (3-8 min depending on the experimental group). Animals were sacrificed at 1 day or 7 days after injury. Functional tests were performed daily for motor, sensory, autonomic, and reflex responses. Lesion histopathology was assessed for lesion length, percentage of residual white matter, and astrocytic reactivity. Experimental groups demonstrated a functional deficit, which was correlated to the increase of the irradiation time and, therefore, to the severity of the injury. Histopathological and immunocytochemical data were reliable morphological measurements characterizing the degree of injury, which were strongly correlated to the severity of the functional impairment. Despite differences in the mechanism of injury, the wound healing response described in other traumatic SCI mice models was confirmed (no cavitation and, conversely, the formation of a dense connective tissue matrix). In this context, the precise understanding of the mechanisms of healing response after SCI in mice and of neurochemical kinetics appear to be crucial in the development of therapeutic strategies of CNS repair. Thus, the possible use of an increasing collection of transgenic mice offers a new dimension for experimental research in this area. The ischemic photochemical model of SCI in mice represents a relevant model that can play a key role in this new era of neurotrauma research.