The Effectiveness of Trigeminal Nerve Stimulation on Traumatic Brain Injury.

OBJECTIVES: Trigeminal nerve stimulation (TNS) is a promising strategy in treating diseases of the nervous system. In this study, the effects of TNS on traumatic brain injury (TBI) were investigated in a mouse model. MATERIALS AND METHODS: TBI was induced using a weight-drop device, and TNS treatment was delivered in the first hour after the TBI. Twenty-four hours later, the mice's behavior, brain edema, and expression of inflammatory factors were tested. Functional magnetic resonance imaging also was used to explore the possible effects of TNS on brain activity. RESULTS: TNS alleviates TBI-induced neurological dysfunction in animal behavior tests, besides protecting the blood-brain barrier and reducing the level of brain edema. TNS also effectively reduces the level of tumor necrosis factor-α and interleukin 6 and downregulates the cleaved caspase-3 signaling pathway. A series of brain areas was found to be possibly regulated by TNS, thus affecting the neural functions of animals. CONCLUSION: This study elucidates the role of TNS as an effective treatment for TBI by inhibiting the occurrence of a secondary brain injury.

Early delivery of human umbilical cord mesenchymal stem cells improves healing in a rat model of Achilles tendinopathy.

Objective: This study aimed to explore the efficacy and optimal delivery time of human umbilical cord mesenchymal stem cells (hUC-MSCs) in treating collagenase-induced Achilles tendinopathy. Methods: Achilles tendinopathy in rats at early or advanced stages was induced by injecting collagenase I into bilateral Achilles tendons. A total of 28 injured rats were injected with a hUC-MSC solution or normal saline into bilateral tendons twice and sampled after 4 weeks for histological staining, gene expression analysis, transmission electron microscope assay and biomechanical testing analysis. Results: The results revealed better histological performance and a larger collagen fiber diameter in the MSC group. mRNA expression of TNF-α, IL-1ß and MMP-3 was lower after MSC transplantation. Early MSC delivery promoted collagen I and TIMP-3 synthesis, and strengthened tendon toughness. Conclusion: hUC-MSCs demonstrated a therapeutic effect in treating collagenase-induced Achilles tendinopathy, particularly in the early stage of tendinopathy.

Trigeminal nerve stimulation restores hippocampal dopamine deficiency to promote cognitive recovery in traumatic brain injury.

Cognitive impairment (CI) is a common neurological disease resulting from traumatic brain injury (TBI). Trigeminal nerve stimulation (TNS) is an emerging, non-invasive, and effective neuromodulation therapy especially for patients suffering from brain function disorders. However, the treatment and recovery mechanisms of TNS remain poorly understood. By using combined advanced technologies, we revealed here that the neuroprotective potential of TNS to improve CI caused by TBI. The study results found that 40 Hz TNS treatment has the ability to improve CI in TBI mice and communicates with central nervous system via the trigeminal ganglion (TG). Transsynaptic virus experiments revealed that TG is connected to the hippocampus (HPC) through the corticotropin-releasing hormone (CRH) neurons of paraventricular hypothalamic nucleus (PVN) and the dopamine transporter (DAT) neurons of substantia nigra pars compacta/ventral tegmental area (SNc/VTA). Mechanistically, the data showed that TNS can increase the release of dopamine in the HPC by activating the following neural circuit: TG→CRH+ PVN→DAT+ SNc/VTA → HPC. Bulk RNA sequencing confirmed changes in the expression of dopamine-related genes in the HPC. This work preliminarily explains the efficacy and mechanism of TNS and adds to the increasing evidence demonstrating that nerve stimulation is an effective method to treat neurological diseases.