Ischemic stroke is a severe cerebrovascular disease with high mortality and morbidity. In recent years, reperfusion treatments based on thrombolytic and thrombectomy are major managements for ischemic stroke patients, and the recanalization time window has been extended to over 24 h. However, with the extension of the time window, the risk of ischemia/reperfusion (I/R) injury following reperfusion therapy becomes a big challenge for patient outcomes. I/R injury leads to neuronal death due to the imbalance in metabolic supply and demand, which is usually related to mitochondrial dysfunction. Mitophagy is a type of selective autophagy referring to the process of specific autophagic elimination of damaged or dysfunctional mitochondria to prevent the generation of excessive reactive oxygen species (ROS) and the subsequent cell death. Recent advances have implicated the protective role of mitophagy in cerebral ischemia is mainly associated with its neuroprotective effects in I/R injury. This review discusses the involvement of mitochondria dynamics and mitophagy in the pathophysiology of ischemic stroke and I/R injury in particular, focusing on the therapeutic potential of mitophagy regulation and the possibility of using mitophagy-related interventions as an adjunctive approach for neuroprotective time window extension after ischemic stroke.

Aim: To determine the effect of osteopontin (OPN) on autophagy and autophagy‐apoptosis interactions after SAH.Methods: The endovascular perforation model of SAH or sham surgery was performed in a total of 86 Sprague‐Dawley male rats. The temporal expressions of endogenous OPN and autophagy‐related proteins (Beclin 1, ATG5, LC3 II to I ratio) were measured in sham and SAH rats at different time points (3, 6, 12, 24, and 72 hours). Rats were randomly divided into three groups: Sham, SAH + Vehicle (PBS, phosphate‐buffered saline), and SAH + rOPN (5 μg/rat recombinant OPN). Neurobehavioral tests were performed 24 hours after SAH, followed by the collection of brain samples for assessment of autophagy and apoptosis proteins. These tests assessed whether an autophagy‐apoptosis relationship existed on the histological level in the brain.Results: Endogenous OPN and autophagy‐related proteins all increased after SAH. rOPN administration improved neurological dysfunction, increased the expression of autophagy‐related proteins (Beclin 1, ATG5, LC3 II to I ratio) and antiapoptotic protein Bcl‐2, while decreasing the expression of proapoptotic proteins (cleaved Caspase‐3 and Bax). rOPN also regulated autophagy‐apoptosis interactions 24 hours after SAH.Conclusion: rOPN attenuates early brain injury and inhibits neuronal apoptosis by activating autophagy and regulating autophagy‐apoptosis interactions.

Osteopontin (OPN) enhances autophagy, reduces apoptosis, and attenuates early brain injury (EBI) after a subarachnoid hemorrhage (SAH). A total of 87 Sprague–Dawley rats were subjected to sham or SAH operations to further investigate the signaling pathway involved in osteopontin-enhanced autophagy during EBI, and the potential effect of recombinant OPN (rOPN) administration to improve long-term outcomes after SAH. Rats were randomly divided into five groups: Sham, SAH + Vehicle (PBS, phosphate-buffered saline), SAH + rOPN (5 μg/rat recombinant OPN), SAH + rOPN + Fib-14 (30 mg/kg of focal adhesion kinase (FAK) inhibitor-14), and SAH + rOPN + DMSO (dimethyl sulfoxide). Short-term and long-term neurobehavior tests were performed, followed by a collection of brain samples for assessment of autophagy markers in neurons, pathway proteins expression, and delayed hippocampal injury. Western blot, double immunofluorescence staining, Nissl staining, and Fluoro-Jade C staining assay were used. Results showed that rOPN administration increased autophagy in neurons and improved neurobehavior in a rat model of SAH. With the administration of FAK inhibitor-14 (Fib-14), neurobehavioral improvement and autophagy enhancement induced by rOPN were abolished, and there were consistent changes in the phosphorylation level of ERK1/2. In addition, early administration of rOPN in rat SAH models improved long-term neurobehavior results, possibly by alleviating hippocampal injury. These results suggest that FAK–ERK signaling may be involved in OPN-enhanced autophagy in the EBI phase after SAH. Early administration of rOPN may be a preventive and therapeutic strategy against delayed brain injury after SAH.

Peripheral nerve injury (PNI) is a clinical problem with high morbidity that can cause severe damage. Surgical suturing or implants are usually required due to the slow speed and numerous factors affecting repair after PNI. An autologous nerve graft is the gold standard for PNI repair among implants. However, there is a potential problem of the functional loss of the donor site. Therefore, tissue-engineered nerve biomaterials are often used to bridge the gap between nerve defects, but the therapeutic effect is insufficient. In order to enhance the repair effect of nerve biomaterials for PNI, researchers are seeking to combine various stimulation elements, such as the addition of biological factors such as nerve growth factors or physical factors such as internal microstructural modifications of catheters and their combined application with physical stimulation therapy. Physical stimulation therapy is safer, is more convenient, and has more practical features than other additive factors. Its feasibility and convenience, when combined with nerve biomaterials, provide broader application prospects for PNI repair, and has therefore become a research hot spot. This paper will review the combined application of physical stimulation and biomaterials in PNI repair in recent years to provide new therapeutic ideas for the future use of physical stimulation in PNI repair.