Parkinson's disease (PD) is a progressive neurodegenerative disease. α-Synuclein (α-syn) oligomers play a critical role in the progression of PD. Baicalein, a typical flavonoid compound, can inhibit the formation of the α-syn oligomers, and disaggregate existing α-syn oligomers in vitro. However, whether baicalein could inhibit or disaggregate α-syn oligomers in vivo has not been investigated. Therefore, this study was designed to investigate the inhibitory effects of baicalein on α-syn oligomers in vivo and to explore the possible mechanisms of such inhibition. A chronic PD mouse model was created by continuous intragastric administration of rotenone (5mg/kg, 12weeks). Baicalein (100mg/kg) was intraperitoneally injected from 7week to 12week. Our result showed that the amount of α-syn, changes in the levels of the striatal neurotransmitters, and the behavioral changes found in the chronic PD mouse model were prevented after the baicalein injections. Although baicalein did not decrease α-syn mRNA expression, α-syn oligomers were significantly decreased in the ileum, thoracic spinal cord, and midbrain. Furthermore, transmission electron microscopy analysis showed that baicalein could prevent α-syn monomers from the oligomer formation in vitro. Taken together, these results suggest that baicalein could prevent the progression of α-syn accumulation in PD mouse model partly by inhibiting formation of the α-syn oligomers.

Neuronal apoptosis after intracerebral hemorrhage (ICH) plays an essential role in neurological deterioration. Preclinical studies have shown that EGb761, an extract of Ginkgo biloba, is neuroprotective in some other neurological diseases with apoptosis. This study was conducted to investigate the potential neuroprotective effect of EGb761 on neuronal apoptosis in experimental ICH. A model of ICH was induced in C57BL/6 mice by injecting collagenase. EGb761 was administered for 21 days and neurologic behaviors were assessed at 1, 3, 7, 14, and 21 days after ICH. RNAi-mediated knockdown of p90 ribosomal S6 kinase 1 (RSK1) was used to further investigate the role of RSK1 in EGb761-induced neuroprotective effects. Neuronal death was determined by TUNEL staining. The image datasets of neurovascular networks were acquired via micro-optical sectioning tomography (MOST). The glycogen synthase kinase-3β (GSK3β) activity was assayed using commercial kit. Primary cultured cortical neurons were exposed to ferrous iron and treated with EGb761. Apoptotic neurons were counted by flow cytometry. RSK1, GSK3β, phosphorylated-GSK3β (pGSK3β), Bcl2, Bax, cleaved-caspase3 (CC3), and VEGF were measured by Western blot. The pGSK3β was also detected by immunofluorescence staining. We found that mice in EGb761 group performed better on rotarod test. Reduced TUNEL-positive neurons and richer microvascular networks were observed in mice treated with EGb761. EGb761 attenuates neuronal apoptosis induced by ferrous iron counted by flow cytometry in vitro. Decreased GSK3β activity was observed in EGb761-treated mice compared with mice with ICH. EGb761 increased the expression of pGSK3β (Ser9), RSK1 and the Bcl2/Bax ratio, and VEGF and decreased CC3 expression. In conclusion, EGb761 reduces neuronal apoptosis and promotes angiogenesis in experimental intracerebral hemorrhage via RSK1/GSK3β pathway.

Stroke is one of the leading causes of death and disability worldwide. Brain injury after ischemic stroke involves multiple pathophysiological mechanisms, such as oxidative stress, mitochondrial dysfunction, excitotoxicity, calcium overload, neuroinflammation, neuronal apoptosis, and blood-brain barrier (BBB) disruption. All of these factors are associated with dysfunctional energy metabolism after stroke. Mitochondria are organelles that provide adenosine triphosphate (ATP) to the cell through oxidative phosphorylation. Mitochondrial dynamics means that the mitochondria are constantly changing and that they maintain the normal physiological functions of the cell through continuous division and fusion. Mitochondrial dynamics are closely associated with various pathophysiological mechanisms of post-stroke brain injury. In this review, we will discuss the role of the molecular mechanisms of mitochondrial dynamics in energy metabolism after ischemic stroke, as well as new strategies to restore energy homeostasis and neural function. Through this, we hope to uncover new therapeutic targets for the treatment of ischemic stroke.