Neuroprotective effects of salidroside on focal cerebral ischemia/reperfusion injury involve the nuclear erythroid 2-related factor 2 pathway

Salidroside,the main active ingredient extracted from Rhodiola crenulata,has been shown to be neuroprotective in ischemic cerebral injury,but the underlying mechanism for this neuroprotection is poorly understood.In the current study,the neuroprotective effect of salidroside on cerebral ischemia-induced oxidative stress and the role of the nuclear factor erythroid 2-related factor 2（Nrf2）pathway was investigated in a rat model of middle cerebral artery occlusion.Salidroside（30 mg/kg）reduced infarct size,improved neurological function and histological changes,increased activity of superoxide dismutase and glutathione-S-transferase,and reduced malon-dialdehyde levels after cerebral ischemia and reperfusion.Furthermore,salidroside apparently increased Nrf2 and heme oxygenase-1 expression.These results suggest that salidroside exerts its neuroprotective effect against cerebral ischemia through anti-oxidant mechanisms and that activation of the Nrf2 pathway is involved.The Nrf2/antioxidant response element pathway may become a new therapeutic target for the treatment of ischemic stroke.

Gualou Guizhi decoction promotes neurological functional recovery and neurogenesis following focal cerebral ischemia/reperfusion

Recovery following stroke involves neurogenesis and axonal remodeling within the ischemic brain. Gualou Guizhi decoction （GLGZD） is a Chinese traditional medicine used for the treatment of post-stroke limb spasm. GLGZD has been reported to have neuroprotective effects in cerebral ischemic injury. However, the effects of GLGZD on neurogenesis and axonal remodeling following cerebral ischemia remain unknown. In this study, a rat model of focal cerebral ischemia/reperfusion was established by middle cerebral artery occlusion. Neurologi- cal function was assessed immediately after reperfusion using Longa＇s 5-point scoring system. The rats were randomly divided into vehicle and GLGZD groups. Rats in the sham group were given sham operation. The rats in the GLGZD group were intragastrically administered GLGZD, once daily, for 14 consecutive days. The rats in the vehicle and sham groups were intragastrically administered distilled water. Modified neurological severity score test, balance beam test and foot fault test were used to assess motor functional changes. Nissl staining was performed to evaluate histopathological changes in the brain. Immunofluorescence staining was used to examine cell proliferation using the marker 5-bromo-2＇-deoxyuridine （BrdU） as well as expression of the neural precursor marker doublecortin （DCX）, the astrocyte marker glial fibrillary acidic protein （GFAP） and the axon regeneration marker growth associated protein-43 （GAP-43）. GLGZD substan- tially mitigated pathological injury, increased the number of BrdU, DCX and GFAP-immunoreactive cells in the subventricular zone of the ischemic hemisphere, increased GAP-43 expression in the cortical peri-infarct region, and improved motor function. These findings suggest that GLGZD promotes neurological functional recovery by increasing cell proliferation, enhancing axonal regeneration, and in- creasing the numbers of neuronal precursors and astrocytes in the peri-infarct area.

Emerging blood exosome-based biomarkers for preclinical and clinical Alzheimer's disease:a meta-analysis and systematic review

Blood exosomes,which are extracellular vesicles secreted by living cells into the circulating blood,are regarded as a relatively noninvasive novel tool for monitoring brain physiology and disease states.An increasing number of blood cargo-loaded exosomes are emerging as potential biomarkers for preclinical and clinical Alzheimer's disease.Therefo re,we conducted a meta-analysis and systematic review of molecular biomarkers derived from blood exosomes to comprehensively analyze their diagnostic performance in preclinical Alzheimer's disease,mild cognitive impairment,and Alzheimer's disease.We performed a literature search in PubMed,Web of Science,Embase,and Cochrane Library from their inception to August 15,2020.The research subjects mainly included Alzheimer's disease,mild cognitive impairment,and preclinical Alzheimer's disease.We identified 34 observational studies,of which 15 were included in the quantitative analysis(Newcastle-Ottawa Scale score 5.87 points)and 19 were used in the qualitative analysis.The meta-analysis results showed that core biomarkers including Aβ_(1-42),P-T181-tau,P-S396-tau,and T-tau were increased in blood neuro nderived exosomes of preclinical Alzheimer's disease,mild cognitive impairment,and Alzheimer's disease patients.M olecules related to additional risk facto rs that are involved in neuroinflammation(C1q),metabolism disorder(P-S312-IRS-1),neurotrophic deficiency(HGF),vascular injury(VEGF-D),and autophagy-lysosomal system dysfunction(cathepsin D)were also increased.At the gene level,the differential expression of transc ription-related factors(REST)and microRNAs(miR-132)also affects RNA splicing,transport,and translation.These pathological changes contribute to neural loss and synaptic dysfunction.The data confirm that the above-mentioned core molecules and additional ris k-related factors in blood exosomes can serve as candidate biomarkers for preclinical and clinical Alzheimer's disease.These findings support further development of exosome biomarkers for a clinical blood test for Alzheimer's disease.This meta-analysis was registered at the International Prospective Register of Systematic Reviews(Registration No.CRD4200173498,28/04/2020).