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Rat Models of Spinal Cord Injury

Rat Models of Spinal Cord Injury

Spinal Cord Injury, or SCI, results from physical trauma to the spinal cord or from medical illness that injures or damages the spinal cord. The spinal cord is a major bundle of nerves that extends from the base of the brain and down the middle of the back, to about the waist. It transmits nerve impulses between the brain and the rest of the body, and together, the brain and the spinal cord constitute the central nervous system (CNS).

While spinal cord injury is rare, with less than 20,000 new cases per year in the U.S., the effects on the patient can be very debilitating, due to loss of motion and strength, changes in body functions, and chronic pain. The patient may also experience mental, emotional, and social challenges due to the injury.

Spinal cord injury may occur due to traumatic damage to the vertebrae, ligaments, or disks of the spinal column, or to the spinal cord itself. The effects of the injury may be experienced immediately; or more gradually, due to additional or continued injury or even due to bleeding and swelling in or around the spinal cord after the initial injury.

While there is currently no cure, scientists are optimistic about research advances toward treatment and repair of spinal cord injuries. Many of the advances involve decreasing the extent of spinal cord damage at the time of injury, such as by reducing swelling that would occur due to the primary injury.

Use of rat models to study spinal cord injury

The aim of spinal cord injury research is to advance and develop treatments for spinal cord repair. Rodents are the most common and best suited species for initial studies of this injury, with the rat spinal cord injury, in particular, effectively modeling the human condition. The rat has become the most commonly used animal model species for investigating spinal cord injury, and particularly in the assessment of biological and behavioral outcomes. Rat models represent an important resource for evaluating treatment strategies and studying the pathological basis of spinal cord injury.

Various treatment options have been studied using rat models. The most effective studies using rats have involved preventing secondary injury and employing efforts to repair spinal circuitry, and reactivating or enhancing the surviving neural pathways. Rat models have been less useful in the study of treatment strategies involving implantable devices for controlling muscles or prostheses, or other devices designed to support locomotion.

To model spinal cord injury in the rat, physical injury methods are generally used, specifically, contusion, transection, or compression.

Genetic rodent models for studying biology of spinal cord injury

Mice have been increasingly used in studies of spinal cord injury and repair, due to the greater relative ease of introducing defined genetic alterations in the mouse. The use of genetically engineered mice has permitted investigations into the roles of specific genes and proteins in biological pathways involved or affected by spinal cord injury. Subsequently, larger animal models may need to be used for evaluating the efficacy and translatability of treatments developed using rodent models.

While creating genetically engineered mice may be more feasible for studying the basic cellular and molecular biology of spinal cord injury, mice are smaller in size than rats and more challenging to use in spinal cord studies involving surgical procedures or devices.

Recent advances in rat genetic engineering, particularly with the application of CRISPR/Cas9 genome editing technology, have improved the feasibility of creating genetic rat models of spinal cord injury. Since rats and mice have differences in spinal cord pathology and recovery, the creation of genetically engineered rat models can lead to significant advances in the research on spinal cord injury and repair.