Spinal cord injuries (SCI), unlike other injuries, often exhibit limited recovery. Patients with SCI often face major detriments to quality of life and health due to impaired motor control, sensation, and homeostatic regulation. In SCI patient surveys, regaining hand function is consistently among the highest priorities. We use a rat model of cervical SCI to develop therapies that restore motor function for reaching and grasping. We have shown that rats that receive targeted, activity-dependent spinal stimulation (TADSS) at a single spinal site for forelimb reaching exhibited enhanced recovery compared to physical retraining or open-loop electrical stimulation. Spinal stimulation is delivered to the injured forelimb of the rat when muscular activity, during reaching and grasping, is displayed. We used the single pellet grasping (SPG) task to assess forelimb function. Our hypothesis was that modifying the TADSS protocol to include stimulation of multiple motor pathways (MTADSS) for reaching and grasping will produce greater recovery than single site TADSS. In the current project, male and female Long-Evans rats were injured with a unilateral C4-C5 spinal hemi-contusion which primarily impairs the dominant forelimb. Four weeks after injury, the animals were implanted with spinal stimulation wires and wires for recording the muscle activity of the impaired forelimb. MTADSS and unstimulated control rats, underwent fourteen weeks of daily SPG, lever pull, which measures pull strength, and two other functional assessments, which will be reported elsewhere. MTADSS rats show recovery in SPG and a principal component analysis of lever pull showed that mean peak force (MPF), explains 84% of the variance between control rats and therapy rats at week 7 of therapy. The increased MPF among MTADSS rats suggests increased muscle recovery due to therapy. Taken together, MTADSS therapy seems to promote recovery in multiple measures of forelimb function compared to physical retraining alone.

More than half of spinal cord injuries (SCI) affect the cervical cord, which can have devastating life-long impairments to hand and arm function. We use a rodent model of cervical spinal contusion to develop activity dependent electrical stimulation therapy for regaining fine motor function after SCI. The Ohio State Injury Device uses an electromagnetic impounder to compress the spinal cord with a 2.5 mm probe and control variables that can affect the severity of the injury, most importantly displacement (i.e. how much the cord is compressed during injury). However, here we show that injury severity varies more than controlling for displacement can account for. We have also investigated the effect of surgeon on injury severity, which appears to have a small influence on injury severity. Upon further analysis, we have found that given similar probe displacements, male rats exhibit greater functional deficits after injury than female rats. Physiological differences such as size and hormone levels vary between males and females and may impact severity of motor function deficits. We hypothesize estrogen levels may influence injury severity. Previous studies have shown administering estrogen to a rat after SCI is neuroprotective and to decrease apoptotic activity in the spinal cord. In our ongoing studies, we will monitor the stage of the estrous cycle (a proxy for measuring estrogen and other hormones) in female rats prior to injury. Investigating the effects of estrogen on SCI helps us develop and understand injury models and motor function after SCI. A more sophisticated injury model may help us develop more effective treatments for SCI. Ultimately, results may help bring novel therapies closer to clinical use.