lucifer-yellow and Spinal-Cord-Injuries

The corticospinal tract in the macaque and human forms the major descending pathway involved in volitional hand movements. Following a unilateral cervical dorsal root lesion, by which sensory input to the first three digits (D1-D3) is removed, monkeys are initially unable to perform a grasp retrieval task requiring sensory feedback. Over several months, however, they recover much of this capability. Past studies in our laboratory have identified a number of changes in the afferent circuitry that occur as function returns, but do changes to the efferent pathways also contribute to compensatory recovery? In this study we examined the role of the corticospinal tract in pathway reorganization following a unilateral cervical dorsal rhizotomy. Several months after animals received a lesion, the corticospinal pathways originating in the primary somatosensory and motor cortex were labeled, and terminal distribution patterns on the two sides of the cervical cord were compared. Tracers were injected only into the region of D1-D3 representation (identified electrophysiologically). We observed a strikingly different terminal labeling pattern post lesion for projections originating in the somatosensory versus motor cortex. The terminal territory from the somatosensory cortex was significantly smaller compared with the contralateral side (area mean = 0.30 vs. 0.55 mm2), indicating retraction or atrophy of terminals. In contrast, the terminal territory from the motor cortex did not shrink, and in three of four animals, aberrant terminal label was observed in the dorsal horn ipsilateral to the lesion, indicating sprouting. These differences suggest that cortical regions play a different role in post-injury recovery

Topics: Action Potentials; Animals; Biotin; Dextrans; Disease Models, Animal; Functional Laterality; Isoquinolines; Macaca fascicularis; Male; Motor Cortex; Neurons; Patch-Clamp Techniques; Presynaptic Terminals; Pyramidal Tracts; Rhizotomy; Somatosensory Cortex; Spinal Cord Injuries; Spinal Nerve Roots; Spinal Nerves

Spinal cord injury (SCI) launches a complex cascade of events that leads to progressive damage and loss of function. Compromise of plasma membrane integrity due to the mechanical impact is an acute event that may contribute to cellular dysfunction. Therefore, the objective of this study was to better understand the extent of acute plasma membrane damage associated with SCI as a function of injury severity and membrane defect size. Fluorescent cell-impermeant dyes were injected into the cerebrospinal fluid of adult male rats prior to contusion injury, and the anatomical location of cell bodies and axons taking up the dye within 10 min following SCI was quantified. Lucifer yellow uptake was assessed as a function of impact force (experimental groups: sham, 100 kdyn, 150 kdyn, and 200 kdyn force). In a separate group of animals, FITC-conjugated dextran molecules of various sizes (3 kDa and 10 kDa with a 1.6-nm and 2.7-nm radius, respectively) were used to approximate the size of membrane defects following moderate injury (150 kdyn force). Quantification revealed that cellular uptake of lucifer yellow was positively correlated with the force of the mechanical impact, indicating that the severity of injury is related to the degree of acute membrane failure. In addition, after moderate injury, cell bodies and axons (located up to 2 mm and 3 mm from the epicenter, respectively) took up significantly more of the 3-kDa and 10-kDa dextran permeability marker compared to sham controls. Permeable neuronal cell bodies exhibited a morphological appearance characterized by pericellular blebbing, suggesting that plasma membrane compromise is associated with pathophysiological cellular alterations. Collectively, these results enhance our understanding of acute SCI and provide targets for developing novel treatment strategies.

Topics: Animals; Axons; Cell Membrane; Cell Membrane Permeability; Dextrans; Disease Models, Animal; Fluorescein-5-isothiocyanate; Isoquinolines; Male; Nerve Degeneration; Neurons; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries; Stress, Mechanical

This study investigated satellite cell changes in mouse L4 and L5 spinal ganglia 14 days after unilateral transection of sciatic and saphenous nerves. The ganglia were studied under the electron microscope in single and serial sections, and by dye injection. Satellite cell responses to axon injury of the neurons with which they are associated included the formation of bridges connecting previously separate perineuronal sheaths and the formation of new gap junctions, resulting in more extensive cell coupling. Some possible consequences of these satellite cell reactions are briefly discussed.

Topics: Animals; Axons; Denervation; Female; Fluorescent Dyes; Ganglia, Spinal; Gap Junctions; Isoquinolines; Male; Mice; Mice, Inbred BALB C; Microscopy, Electron; Neurons; Satellite Cells, Perineuronal; Spinal Cord Injuries