Overexpression of Heme oxygenase 1 enhances the neuroprotective effects of exosomes in subarachnoid hemorrhage by suppressing oxidative stress and endoplasmic reticulum stress

Abstract Aims: To investigate the therapeutic effects and potential mechanism of exosomes from Heme oxygenase 1 (HO-1)-overexpressing human umbilical cord mesenchymal stem cells (ExoHO-1) on subarachnoid hemorrhage (SAH) mice. Methods: Western blotting, particles analyzer, and transmission electron microscopy were used to identify the exosomes. Garcia scoring system, Beam balance, Rotarod test, and Morris water maze test were performed to assessed the effect of ExoHO-1 and ExoCtrl on neurological function of SAH mice. TUNEL and Nissl staining were used to examinate the neuron apoptosis. Immunofluorescence, Western blotting, DHE, Enzyme-linked immunosorbent assay, and commercial kits were used to examine the levels of oxidative stress and endoplasmic reticulum stress. Results: HO-1-overexpressing human umbilical cord mesenchymal stem cells loaded HO-1 into their exosomes. ExoHO-1 exhibited a significantly beneficial effects on short-term and long-term neurological function protecting. By reducing activation of PERK/CHOP/Caspase12 pathway and levels of oxidative stress, ExoHO-1 more effectively inhibited neuronal apoptosis in ipsilateral temporal cortex. Conclusion: HO-1 over-expression enhanced the therapy of exosomes on the SAH mice by against neuronal apoptosis in SAH. These therapeutic effects are likely through suppressing the oxidative stress and endoplasmic reticulum stress.