Figure 1.

TBI pathology and MSC-related treatment mechanisms. When TBI occurs, the BBB is disrupted, leading to a series of responses such as hypoxia, edema, and release of inflammatory factors by immune cells. Excessive production of ROS in neurons and alteration of mitochondrial membrane potential results in a variety of pathological processes, such as oxidative stress, mtDNA damage, mitophagy, and apoptosis, some of which will eventually lead to cell death. Furthermore, they also enable MPTP to open instantly promoting the above pathological processes. When we use MSCs to treat TBI, MSCs and their released exosomes can cross the BBB stably and release various cytokines, such as neurotrophic factors and vascular regeneration factors, to promote nerve and blood vessel repair and regeneration. MSCs can also deliver healthy mitochondria to neurons through TNTs to enhance the anti-inflammatory, antioxidant, and antiapoptotic abilities of neurons and eventually improve their functions. BBB: blood-brain barrier; MSC: mesenchymal stromal cell; MPTP: mitochondrial permeability transition pores; mtDNA: mitochondrial DNA; ROS: reactive oxygen species; TBI: traumatic brain injury; TNT: tunneling nanotubes.