Dynamic changes in Beclin-1, LC3B, and p62 in aldose reductase-knockout mice at different time points after ischemic stroke

Ischemic stroke is a brain injury caused by cerebral blood circulation disorders and is closely related to oxidative stress. Aldose reductase (AR) is a critical enzyme involved in oxidative stress. Autophagy has previously been found to play a key role in cerebral ischemia‒reperfusion injury. However, it is still unclear how autophagy molecules change after cerebral ischemia‒reperfusion injury in AR knockout mice (AR^-/-). A transient middle cerebral artery occlusion (tMCAO) model was generated in AR^-/- mice, and the neurological deficit scores of the mice were observed and recorded on Days 1, 3 and 5 after tMCAO. Neuronal damage in the ischemic penumbra was observed by TTC, HE, and Nissl staining. The expression of the autophagy-related molecules Beclin-1, LC3II/I, and P62 as well as that of molecules related to inflammation, oxidative stress, and neurological damage was detected by RT‒qPCR, western blotting, and immunofluorescence. Autophagosomes were observed using a transmission electron microscope. Cerebral ischemia‒reperfusion injury caused neurological deficits and ischemic infarction in tMCAO mice (<i>P</i> < 0.01). Beclin-1, Bcl2/Bax, SOD, GSH-px, P62, PSD95, and TOM20 levels decreased (<i>P</i> < 0.05), while IL-6, LC3II/I, and GFAP levels increased (<i>P</i> < 0.01) in the AR^-/- tMCAO-1d group and the AR^-/- tMCAO-3d group, compared to those in the sham group. Beclin-1, Bcl2/Bax, NOX4, GSH-px, P62, and PSD95 levels increased (<i>P</i> < 0.01), while IL-6, LC3II/I, and GFAP levels decreased (<i>P</i> < 0.01) in the AR^-/- tMCAO-5d group compared to those in the AR^-/- tMCAO-1d group. Autophagosome formation was observed in tMCAO mice. In summary, the changes in autophagy proteins in the brain tissue of the AR^-/- mice after tMCAO were more obvious on Days 1 and 3 after tMCAO. The expression of Beclin-1 and P62 decreased, and the expression of LC3B increased after cerebral ischemia‒reperfusion injury in AR^-/- mouse brain tissue.