Chrystine Gallegos

The University of Texas Health Science Center at Houston

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Yiyan Zheng

Fujian Medical University

Qilin Cao

Jilin University

Qi Lin Cao

Florida International University

Marcia K. O’Malley

Rice University

Andrew Erwin

University of Southern California

Shenglan Li

Capital Medical University

Haipeng Xue

Affiliated Hospital of Shandong University of Traditional Chinese Medicine

Hongxia Zhou

Huangshan University

Xiuquan He

Minzu University of China

Dong Kim

Seoul National University

Cooperative Institutions

Brown Foundation

The University of Texas Health Science Center at Houston

Florida International University

Shandong University

Rice University

Interface (United States)

Escuela Superior Politecnica del Litoral

John Radcliffe Hospital

University of Oxford

Capital Medical University

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Validation of a 3DOF parallel manipulator for robotic forelimb training with rats

Andrew Erwin Chrystine Gallegos Ian Baker Yiyan Zheng Christopher Janßen

Spinal cord injury patients undergoing clinical treatment using robots to deliver rehabilitation have seen mixed functional gains. As a result, researchers have begun exploring combinatorial treatment options in an attempt to promote greater functional recovery. Since these treatment methods are in their nascent stages and would be difficult to apply in the variable injury types found in the human population, rodent models have been proposed for initial investigations. In an attempt at elucidating the impacts of rehabilitation, robotic devices have recently been created for rodents. These devices have primarily focused on rehabilitation in hind limb functional recovery at the thoracic level; however, the majority of human spinal cord injury patients exhibit injury at the cervical level, adversely affecting hand function and severely impairing total mobility and independence.

Forelimb

10.1109/werob.2017.8383867

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Apart and back again: Reestablished neuronal connections restore walking after paralysis

Cell stem cell (2023)

Qi Lin Cao Chrystine Gallegos Yiyan Zheng

10.1016/j.stem.2023.11.003

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Reaching and Grasping Training Improves Functional Recovery After Chronic Cervical Spinal Cord Injury

Frontiers in Cellular Neuroscience (2020)

Chrystine Gallegos Matthew Carey Yiyan Zheng Xiuquan He Qi Lin Cao

Previous studies suggest locomotion training could be an effective non-invasive therapy after spinal cord injury (SCI) using primarily acute thoracic injuries. However, the majority of SCI patients have chronic cervical injuries. Regaining hand function could significantly increase their quality of life. In this study, we used a clinically relevant chronic cervical contusion to study the therapeutic efficacy of rehabilitation in forelimb functional recovery. Nude rats received a moderate C5 unilateral contusive injury and were then divided into two groups with or without Modified Montoya Staircase (MMS) rehabilitation. For the rehabilitation group, rats were trained 5 days a week starting at 8 weeks post-injury (PI) for 6 weeks. All rats were assessed for skilled forelimb functions with MMS test weekly and for untrained gross forelimb locomotion with grooming and horizontal ladder (HL) tests biweekly. Our results showed that MMS rehabilitation significantly increased the number of pellets taken at 13 and 14 weeks PI and the accuracy rates at 12 to 14 weeks PI. However, there were no significant differences in the grooming scores or the percentage of HL missteps at any time point. Histological analyses revealed that MMS rehabilitation significantly increased the number of serotonergic fibers and the amount of presynaptic terminals around motor neurons in the cervical ventral horns caudal to the injury and reduced glial fibrillary acidic protein (GFAP)-immunoreactive astrogliosis in spinal cords caudal to the lesion. This study shows that MMS rehabilitation can modify the injury environment, promote axonal sprouting and synaptic plasticity, and importantly, improve reaching and grasping functions in the forelimb, supporting the therapeutic potential of task-specific rehabilitation for functional recovery after chronic SCI.

10.3389/fncel.2020.00110

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Transplantation of Human Induced Pluripotent Stem Cell-Derived Neural Progenitor Cells Promotes Forelimb Functional Recovery after Cervical Spinal Cord Injury

Cells (2022)

Yiyan Zheng Chrystine Gallegos Haipeng Xue Shenglan Li Dong Kim

Locomotor function after spinal cord injury (SCI) is critical for assessing recovery. Currently, available means to improve locomotor function include surgery, physical therapy rehabilitation and exoskeleton. Stem cell therapy with neural progenitor cells (NPCs) transplantation is a promising reparative strategy. Along this line, patient-specific induced pluripotent stem cells (iPSCs) are a remarkable autologous cell source, which offer many advantages including: great potential to generate isografts avoiding immunosuppression; the availability of a variety of somatic cells without ethical controversy related to embryo use; and vast differentiation. In this current work, to realize the therapeutic potential of iPSC-NPCs for the treatment of SCI, we transplanted purified iPSCs-derived NPCs into a cervical contusion SCI rat model. Our results showed that the iPSC-NPCs were able to survive and differentiate into both neurons and astrocytes and, importantly, improve forelimb locomotor function as assessed by the grooming task and horizontal ladder test. Purified iPSC-NPCs represent a promising cell type that could be further tested and developed into a clinically useful cell source for targeted cell therapy for cervical SCI patients.

Forelimb

Stem Cell Therapy

Cell therapy

10.3390/cells11172765

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Citations (13)

Histological and functional characterization of cervical spinal cord injury after graded contusion

Chrystine Gallegos

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A Robotic Platform for 3D Forelimb Rehabilitation with Rats

Andrew Erwin Chrystine Gallegos Qilin Cao Marcia K. O’Malley

In an attempt to promote greater functional recovery after spinal cord injury, researchers have begun exploring combinatorial treatments, such as robotic rehabilitation combined with stem cell transplantation. Since these treatment methods are in their nascent stages, rodent models have been proposed for initial investigations. Robots have been built for locomotion rehabilitation and planar forelimb reach and grasp assessment with rodents; however, a robotic platform suitable for three-dimensional movement rehabilitation of the rodent forelimb has not yet been developed. In this paper, a novel three degree of freedom robotic manipulator for automated forelimb rehabilitation combined with stem cell transplantation after cervical spinal cord injury with rats is proposed. The robot interfaces with a rat in an end-effector manner, measuring and interacting with the forelimb in the 3D Cartesian space. In this work, we trained two rats through behavioral shaping to actively interact with the device during two robot control modes. This work provides preliminary investigations into the feasibility of 3D forelimb rehabilitation with rats, which could be translated as a paradigm for combinatorial treatments after spinal cord injury in a controlled manner.

Forelimb

Robot end effector

10.1109/icorr.2019.8779405

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Citations (2)