Dendritic Remodeling of the Spinal Motor Neurons in the Denervated Gray Matter After Stroke in Mice

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Conference Proceeding

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J Cereb Blood Flow Metab


Objective: We investigated morphological dendritic changes of the spinal motor neurons, the final common pathway of motor control, during recovery after stroke in adult mice. Methods: Mice (C57BL/6J, 2-3 month-old) were subjected to permanent right unilateral middle cerebral artery occlusion (MCAo) by advancing an 8-0 surgical nylon suture with an expanded silicone tip from the external carotid artery (ECA) into the lumen of the internal carotid artery under isoflurane anesthesia, to block the origin of the MCA. Animals were sacrificed at 7,14, 21 and 28 days after MCAo (n = 12/group), respectively. A separate group of naïve mice was used for normal control (n = 12). Four mice in each group were randomly selected to receive intramuscular injection of pseudorabies virus (PRV)-512-EGFP or AAV-retro into the left forelimb wrist extensor and flexor muscles with a 10μl total volume (1 × 1010 viral particles) through a skin incision at 56 hours or 21 days before sacrifice, respectively. Spinal cord samples were processed for longitudinal vibra-tome sectioning. EGFP labeling in the spinal motor neurons were digitized using a laser-scanning confocal imaging system. Cervical cord samples form the remaining 4 mice were processed for Golgi staining to assess the dendrites and synaptic spines of the spinal motor neurons in the denervated side of the spinal gray matter. NeuronJ, a plugin of NIH software ImageJ, was used to measure dendrite length, branch number and spine density of the spinal motor neurons. Results: Compared to normal control, significant increases of both neurite length and branch numbers were observed in animal groups of 14 days after MCAo with PRV tracing, AAV tracing and Golgi staining, as well as increased dendritic spine density in animal groups of 21 and 28 days after MCAo (P < 0.05). Conclusion: Our data indicate the presence of anatomical remodeling of the spinal motor neurons in the denervated side of the spinal cord post stroke. This remodeling may facilitate rewiring of the stroke-impaired corticospinal innervation, and thereby promote spontaneous motor functional recovery after stroke. These data also suggest that anatomical remodeling of the spinal motor neurons represent a therapeutic target for treatment of stroke.





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