Regular ArticleBehavioral and anatomical consequences of repetitive mild thoracic spinal cord contusion injury in the rat
Introduction
Injuries to the spinal cord result in functional deficits, which depend on the severity and level of injury. Various animal models for spinal cord injury (SCI) including contusion, compression, transection, and hemisection have been developed and used depending upon the experimental goals of the study. Among these injuries, contusion injuries are the most common in human SCI. Contusion lesions created by a computer controlled impactor can be designed to be mild, moderate, or severe (Basso et al., 1996). While moderate and severe contusion injuries have been extensively studied, much less is known about the consequences of mild injuries. A mild injury, clinically defined as a spinal cord concussion, results in transient neurologic disturbances with deficits in sensory and motor function. A complete neurological recovery usually occurs within two to three weeks in animal mild contusion models (Basso et al., 1995, Basso et al., 1996, Scheff et al., 2003, Zhang et al., 2008), but the long term consequences of the injury are not known. Importantly, there is a long clinical history of spinal cord concussion, though it has assumed a variety of clinical terms, including transient paraplegia/quadriplegia/paresis, transient traumatic paraplegia/quadriplegia, neurapraxia, and spinal cord concussion (Brigham and Capo, 2013, Cantu and Cantu, 2005, Maroon et al., 2007, Torg et al., 1997, Torreman et al., 1996, Winder et al., 2011, Zwimpfer and Bernstein, 1990). Both pediatric and adult patients experience transient motor and sensory dysfunction following an acute blow to the cervical or thoracic spinal cord that gradually resolves over a period of 10 min to 48 h, without any radiological abnormalities observed within the spinal cord itself. Most patients sustain injuries following participation in a diverse array of contact sport activity, including American football, rugby, hockey, and wrestling, with the highest incidence rate occurring in American football — approximately 1.3 cases per 10,000, though this likely represents a significant underrepresentation due to failed reporting (Torg et al., 1986). Repeated spinal cord concussions are well known to occur, and numerous reports have documented increased recovery times, progressive neurological damage, and complete paralysis upon secondary concussion.
Unlike spinal cord concussion, brain concussions (mild traumatic brain injuries, mTBIs) have been studied extensively, as hundreds of thousands of sport- and combat-related injuries occur each year (Dietrich et al., 1994, Johnson et al., 2010, Povlishock et al., 1983, Prins et al., 2010). Although mTBI is usually not life threatening, their effects can have serious consequences. People who have had one concussion are more susceptible to another, especially if the new injury occurs before symptoms from the previous concussion have been completely resolved (Gronwall and Wrightson, 1974). In addition, there is also a negative progressive process in which smaller impacts cause the same symptom severity. Repeated concussions may also increase the risk in later life for dementia, Parkinson's disease, and/or depression (Mannix et al., 2013, Plassman et al., 2000). Animal studies indicate a complex pathology that includes the disruption of neuronal cell membrane accompanied by release of glutamate and a lower metabolic state which may persist for weeks after injury (Giza and Hovda, 2001). The efforts to increase awareness about symptoms of mTBI and how to manage them have culminated in the Zurich Consensus Statement on Concussion in Sport, which recommends persons to be symptom free before restarting activity, and then not all at once, but rather through a series of graded steps (McCrory et al., 2009).
Thus far, there have been no comparable studies on the effects and risks of repeated mild SCI in animal models. For example, it is not clear whether repeated mild contusion SCI results in cumulative or synergistic effects, with detrimental consequences on the potential for functional recovery, and whether the increased vulnerability is associated with specific biochemical, immunological, or histological changes. In this study, we addressed these issues in an established animal model, mild spinal cord contusion using the NYU-MASCIS (New York University — Multicenter Animal Spinal Cord Injury Study) impactor. Our findings indicate that even when the second injury occurs following the completion of recovery, the resulting deficits in both motor and sensory functions worsen, and there is no longer recovery to the same levels as the first injury.
Section snippets
Animals
Female Sprague–Dawley rats (225–250 g) were obtained from Taconic Farms (Germantown, NJ). They were housed 3 per cage with a 12 h light/dark cycle. Food and water were available ad libitum. All procedures were approved by the Institutional Animal Care and Use Committee of Drexel University College of Medicine and were carried out according to the NIH Guide for the Care and Use of Laboratory Animals.
Surgical procedure
Twenty five rats received a mild contusion and were divided into two groups three weeks
Open-field locomotion (BBB)
Locomotion, as assessed by the BBB, established that the baseline for all animals before any of the procedures was 21 (Fig. 1). Mild contusion at T10 resulted in functional deficits observed after injury and was examined using BBB at 2–3 days post-injury (BBB: 10 ± 2 in C1, 11 ± 2 in C2, mean ± SD) with gradual recovery to near normal levels (BBB: 19 ± 2 in C1, 19 ± 1 in C2) by 3 weeks post-injury. Following recovery, animals were divided into two groups, each with an average BBB score of 19; C1, for
Discussion
Spinal cord concussion, a variant of mild spinal cord contusion, is a commonly recognized clinical phenotype that has assumed a variety of clinical designations, including transient paraplegia, transient traumatic paraplegia/quadriplegia, transient paraplegia/quadriplegia/paresis, neurapraxia, and spinal cord concussion (Brigham and Capo, 2013, Cantu and Cantu, 2005, Maroon et al., 2007, Torg et al., 1997, Torreman et al., 1996, Winder et al., 2011, Zwimpfer and Bernstein, 1990). Nevertheless,
Conclusion
In summary, the present study demonstrates that mild contusion, created by the NYU impactor, results in transient functional deficits, with recovery to near normal levels by 3 weeks after initial injury. Repeated contusion after functional recovery caused worsening of the deficits that were unable to recover back the levels seen after recovery from the first injury. The degree of the functional deficits appears to be related to the extension of lesion area and increases in inflammation and
Acknowledgments
We thank Theresa Connors for her technical support. This work was supported by NIH grant (PO1 NS055976).
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