Autor: |
Faw TD; 1 Neuroscience Graduate Program, The Ohio State University , Columbus, Ohio.; 2 School of Health and Rehabilitation Sciences, The Ohio State University , Columbus, Ohio.; 3 Center for Brain and Spinal Cord Repair, The Ohio State University , Columbus, Ohio., Lerch JK; 3 Center for Brain and Spinal Cord Repair, The Ohio State University , Columbus, Ohio.; 4 Department of Neuroscience, The Ohio State University , Columbus, Ohio., Thaxton TT; 2 School of Health and Rehabilitation Sciences, The Ohio State University , Columbus, Ohio.; 3 Center for Brain and Spinal Cord Repair, The Ohio State University , Columbus, Ohio., Deibert RJ; 2 School of Health and Rehabilitation Sciences, The Ohio State University , Columbus, Ohio.; 3 Center for Brain and Spinal Cord Repair, The Ohio State University , Columbus, Ohio., Fisher LC; 2 School of Health and Rehabilitation Sciences, The Ohio State University , Columbus, Ohio.; 3 Center for Brain and Spinal Cord Repair, The Ohio State University , Columbus, Ohio., Basso DM; 2 School of Health and Rehabilitation Sciences, The Ohio State University , Columbus, Ohio.; 3 Center for Brain and Spinal Cord Repair, The Ohio State University , Columbus, Ohio. |
Abstrakt: |
Sensorimotor recovery after spinal cord injury (SCI) is of utmost importance to injured individuals and will rely on improved understanding of SCI pathology and recovery. Novel transgenic mouse lines facilitate discovery, but must be understood to be effective. The purpose of this study was to characterize the sensory and motor behavior of a common transgenic mouse line (Thy1-GFP-M) before and after SCI. Thy1-GFP-M positive (TG+) mice and their transgene negative littermates (TG-) were acquired from two sources (in-house colony, n = 32, Jackson Laboratories, n = 4). C57BL/6J wild-type (WT) mice (Jackson Laboratories, n = 10) were strain controls. Moderate-severe T9 contusion (SCI) or transection (TX) occurred in TG+ (SCI, n = 25, TX, n = 5), TG- (SCI, n = 5), and WT (SCI, n = 10) mice. To determine responsiveness to rehabilitation, a cohort of TG+ mice with SCI (n = 4) had flat treadmill (TM) training 42-49 days post-injury (dpi). To characterize recovery, we performed Basso Mouse Scale, Grid Walk, von Frey Hair, and Plantar Heat Testing before and out to day 42 post-SCI. Open field locomotion was significantly better in the Thy1 SCI groups (TG+ and TG-) compared with WT by 7 dpi (p < 0.01) and was maintained through 42 dpi (p < 0.01). These unexpected locomotor gains were not apparent during grid walking, indicating severe impairment of precise motor control. Thy1 derived mice were hypersensitive to mechanical stimuli at baseline (p < 0.05). After SCI, mechanical hyposensitivity emerged in Thy1 derived groups (p < 0.001), while thermal hyperalgesia occurred in all groups (p < 0.001). Importantly, consistent findings across TG+ and TG- groups suggest that the effects are mediated by the genetic background rather than transgene manipulation itself. Surprisingly, TM training restored mechanical and thermal sensation to baseline levels in TG+ mice with SCI. This behavioral profile and responsiveness to chronic training will be important to consider when choosing models to study the mechanisms underlying sensorimotor recovery after SCI. |