Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

Automated monitoring of early neurobehavioral changes in mice following traumatic brain injury

Traumatic brain injury often causes a variety of behavioral and emotional impairments that can develop into chronic disorders. Therefore, there is a need to shift towards identifying early symptoms that can aid in the prediction of traumatic brain injury outcomes and behavioral endpoints in patients with traumatic brain injury after early interventions. In this study, we used the Smart Cage system, an automated quantitative approach to assess behavior alterations in mice during an early phase of traumatic brain injury in their home cages. Female C57BL/6 adult mice were subjected to moderate controlled cortical impact（CCI） injury. The mice then received a battery of behavioral assessments including neurological score, locomotor activity, sleep/wake states, and anxiety-like behaviors on days 1, 2, and 7 after CCI. Histological analysis was performed on day 7 after the last assessment. Spontaneous activities on days 1 and 2 after injury were significantly decreased in the CCI group. The average percentage of sleep time spent in both dark and light cycles were significantly higher in the CCI group than in the sham group. For anxiety-like behaviors, the time spent in a light compartment and the number of transitions between the dark/light compartments were all significantly reduced in the CCI group than in the sham group. In addition, the mice suffering from CCI exhibited a preference of staying in the dark compartment of a dark/light cage. The CCI mice showed reduced neurological score and histological abnormalities, which are well correlated to the automated behavioral assessments. Our findings demonstrate that the automated Smart Cage system provides sensitive and objective measures for early behavior changes in mice following traumatic brain injury.

基于电刺激的导电水凝胶用于糖尿病伤口修复中的免疫调节、神经再生和快速血管生成

糖尿病创面是难以愈合的慢性创面,主要由创面感染、过度炎症、糖尿病神经病变、外周血管病变等引起.因此,全面改善糖尿病创面愈合在临床上具有重要意义.然而,目前对糖尿病创面的研究主要集中在创面感染和血管生成方面,缺乏对神经再生和免疫调节的探索.在这项研究中,我们开发了多功能导电水凝胶作为一种有效的伤口敷料.该水凝胶具有多种功能,包括优异的机械性能、组织粘附性、导电性和广谱抗菌活性.受内源性电场的启发,我们提出了将水凝胶与电刺激相结合的策略来加速糖尿病伤口的愈合.值得注意的是,电刺激结合导电水凝胶的治疗手段可有效促进神经修复,实现巨噬细胞向M2表型的极化以及快速血管生成,从而全面改善糖尿病创面的愈合.这种先进的协作策略为治疗糖尿病伤口开辟了一种新途径.