Hypothermia is currently the only approved
therapy for global
cerebral ischemia (GCI) after
cardiac arrest; however, it unfortunately has multiple adverse effects. As a noninvasive procedure,
photobiomodulation (
PBM)
therapy has emerged as a potential novel treatment for
brain injury.
PBM involves the use of low-level
laser light therapy to influence cell behavior. In this study, we evaluated the
therapeutic effects of
PBM treatment with an 808-nm
diode laser initiated 6 h after GCI. It was noted that
PBM dose-dependently protected against GCI-induced neuronal death in the vulnerable hippocampal CA1 subregion. Functional assessments demonstrated that
PBM markedly preserved both short-term (a week) and long-term (6 months) spatial learning and memory function following GCI. Further mechanistic studies revealed that
PBM post-treatment (a) preserved healthy mitochondrial dynamics and suppressed substantial mitochondrial fragmentation of CA1 neurons, by reducing the detrimental Drp1
GTPase activity and its interactions with adaptor
proteins Mff and Fis1 and by balancing mitochondrial targeting fission and fusion
protein levels; (b) reduced mitochondrial oxidative damage and excessive mitophagy and restored mitochondrial overall health status and preserved mitochondrial function; and (c) suppressed mitochondria-dependent
apoptosome formation/
caspase-3/9 apoptosis-processing activities. Additionally, we validated, in an in vitro
ischemia model, that
cytochrome c oxidase served as a key
PBM target for mitochondrial function preservation and neuroprotection. Our findings suggest that
PBM serves as a promising therapeutic strategy for the functional recovery after GCI, with mechanisms involving
PBM's preservation on mitochondrial dynamics and functions and the inhibition of delayed apoptotic neuronal death in GCI.