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Transplantation of glutamatergic neuronal precursor cells in the paraventricular thalamus and claustrum facilitates awakening with recovery of consciousness

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机构： [1]Department of Neurosurgery, The First Affiliated Hospital, Neurosurgery Research Institute, Fujian Medical University, Fuzhou, Fujian, China. [2]Department of Neurosurgery, State Key laboratory of Medical Neurobiology, Shanghai Key Laboratory of Brain Function and Regeneration, Shanghai Medical College, Fudan University Huashan Hospital, Institute of Brain Science, Fudan University, Shanghai, China. [3]Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China. [4]Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China. [5]Department of Neurology, Peking University Third Hospital, Beijing, China.

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关键词： claustrum disorders of consciousness glutamatergic neuronal precursor cells paraventricular thalamus stem cell transplant traumatic brain injury

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Stem cells offer a promising therapeutic strategy for patients with disorders of consciousness (DOC) after severe traumatic brain injury (TBI), but the optimal transplantation sites and cells are not clear. Although the paraventricular thalamus (PVT) and claustrum (CLA) are associated with consciousness and are candidate transplantation targets, few studies have been designed to investigate this possibility.Controlled cortical injury (CCI) was performed to establish a mouse model of DOC. CCI-DOC paradigm was established to investigate the role of excitatory neurons of PVT and CLA in disorders of consciousness. The role of excitatory neuron transplantation in promoting arousal and recovery of consciousness was determined by optogenetics, chemogenetics, electrophysiology, Western blot, RT-PCR, double immunofluorescence labeling, and neurobehavioral experiments.After CCI-DOC, neuronal apoptosis was found to be concentrated in the PVT and CLA. Prolonged awaking latency and cognitive decline were also seen after destruction of the PVT and CLA, suggesting that the PVT and CLA may be key nuclei in DOC. Awaking latency and cognitive performance could be altered by inhibiting or activating excitatory neurons, implying that excitatory neurons may play an important role in DOC. Furthermore, we found that the PVT and CLA function differently, with the PVT mainly involved in arousal maintenance while the CLA plays a role mainly in the generation of conscious content. Finally, we found that by transplanting excitatory neuron precursor cells in the PVT and CLA, respectively, we could facilitate awakening with recovery of consciousness, which was mainly manifested by shortened awaking latency, reduced duration of loss of consciousness (LOC), enhanced cognitive ability, enhanced memory, and improved limb sensation.In this study, we found that the deterioration in the level and content of consciousness after TBI was associated with a large reduction in glutamatergic neurons within the PVT and CLA. Transplantation of glutamatergic neuronal precursor cells could play a beneficial role in promoting arousal and recovery of consciousness. Thus, these findings have the potential to provide a favorable basis for promoting awakening and recovery in patients with DOC.© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.

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出版当年[2022]版：

大类 | 1 区

医学

小类 | 1 区药学 1 区神经科学

最新[2025]版：

大类 | 2 区医学

小类 | 2 区药学 3 区神经科学

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第一作者机构： [1]Department of Neurosurgery, The First Affiliated Hospital, Neurosurgery Research Institute, Fujian Medical University, Fuzhou, Fujian, China. [2]Department of Neurosurgery, State Key laboratory of Medical Neurobiology, Shanghai Key Laboratory of Brain Function and Regeneration, Shanghai Medical College, Fudan University Huashan Hospital, Institute of Brain Science, Fudan University, Shanghai, China. [*1]Department of Neurosurgery, The First Affiliated Hospital, Neurosurgery Research Institute, Fujian Medical University, Fuzhou, Fujian, China.

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通讯机构： [1]Department of Neurosurgery, The First Affiliated Hospital, Neurosurgery Research Institute, Fujian Medical University, Fuzhou, Fujian, China. [2]Department of Neurosurgery, State Key laboratory of Medical Neurobiology, Shanghai Key Laboratory of Brain Function and Regeneration, Shanghai Medical College, Fudan University Huashan Hospital, Institute of Brain Science, Fudan University, Shanghai, China. [*1]Department of Neurosurgery, The First Affiliated Hospital, Neurosurgery Research Institute, Fujian Medical University, Fuzhou, Fujian, China. [*2]Department of Neurosurgery, State Key laboratory of Medical Neurobiology, Shanghai Key Laboratory of Brain Function and Regeneration, Shanghai Medical College, Fudan University Huashan Hospital, Institute of Brain Science, Fudan University, No. 12 Urumqi Mid Road, Shanghai 200040, China.

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Transplantation of glutamatergic neuronal precursor cells in the paraventricular thalamus and claustrum facilitates awakening with recovery of consciousness

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