The endogenous proteoglycan-degrading enzyme ADAMTS-4 promotes functional recovery after spinal cord injury

<p>Abstract</p> <p>Background</p> <p>Chondroitin sulfate proteoglycans are major inhibitory molecules for neural plasticity under both physiological and pathological conditions. The chondroitin sulfate degrading enzyme chondroitinase ABC promotes functional recovery after spinal cord injury, and restores experience-dependent plasticity, such as ocular dominance plasticity and fear erasure plasticity, in adult rodents. These data suggest that the sugar chain in a proteoglycan moiety is essential for the inhibitory activity of proteoglycans. However, the significance of the core protein has not been studied extensively. Furthermore, considering that chondroitinase ABC is derived from bacteria, a mammalian endogenous enzyme which can inactivate the proteoglycans' activity is desirable for clinical use.</p> <p>Methods</p> <p>The degradation activity of ADAMTS-4 was estimated for the core proteins of chondroitin sulfate proteoglycans, that is, brevican, neurocan and phosphacan. To evaluate the biological significance of ADMATS-4 activity, an <it>in vitro </it>neurite growth assay and an <it>in vivo </it>neuronal injury model, spinal cord contusion injury, were employed.</p> <p>Results</p> <p>ADAMTS-4 digested proteoglycans, and reversed their inhibition of neurite outgrowth. Local administration of ADAMTS-4 significantly promoted motor function recovery after spinal cord injury. Supporting these findings, the ADAMTS-4-treated spinal cord exhibited enhanced axonal regeneration/sprouting after spinal cord injury.</p> <p>Conclusions</p> <p>Our data suggest that the core protein in a proteoglycan moiety is also important for the inhibition of neural plasticity, and provides a potentially safer tool for the treatment of neuronal injuries.</p

Cortical activity associated with the maintenance of balance during unstable stances

Background Humans continuously maintain and adjust posture during gait, standing, and sitting. The difficulty of postural control is reportedly increased during unstable stances, such as unipedal standing and with closed eyes. Although balance is slightly impaired in healthy young adults in such unstable stances, they rarely fall. The brain recognizes the change in sensory inputs and outputs motor commands to the musculoskeletal system. However, such changes in cortical activity associated with the maintenance of balance following periods of instability require further clarified. Methods In this study, a total of 15 male participants performed two postural control tasks and the center of pressure displacement and electroencephalogram were simultaneously measured. In addition, the correlation between amplitude of center of pressure displacement and power spectral density of electroencephalogram was analyzed. Results The movement of the center of pressure was larger in unipedal standing than in bipedal standing under both eye open and eye closed conditions. It was also larger under the eye closed condition compared with when the eyes were open in unipedal standing. The amplitude of high-frequency bandwidth (1–3 Hz) of the center of pressure displacement was larger during more difficult postural tasks than during easier ones, suggesting that the continuous maintenance of posture was required. The power spectral densities of the theta activity in the frontal area and the gamma activity in the parietal area were higher during more difficult postural tasks than during easier ones across two postural control tasks, and these correlate with the increase in amplitude of high-frequency bandwidth of the center of pressure displacement. Conclusions Taken together, specific activation patterns of the neocortex are suggested to be important for the postural maintenance during unstable stances