Affiliation:
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
Abstract
AbstractBackgroundStem 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.MethodsControlled 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.ResultsAfter 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.ConclusionIn 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.
Funder
National Natural Science Foundation of China
National Science and Technology Major Project
Subject
Pharmacology (medical),Physiology (medical),Psychiatry and Mental health,Pharmacology
Cited by
3 articles.
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