Abstract
Background/Aims Naomaitai can improve blood perfusion and ameliorate the damage in the paraventricular white matter. This study was focused on observing the neuroprotective effect of Naomaitai on the vascular dementia of rat and exploring the action mechanism of PI3K/PDK1/AKT signaling pathway. Methods A vascular dementia model of rats was established by permanent, bilateral common carotid artery occlusion. Rats' behavior was tested by Neurological deficit score and the Morris water maze. The pathology and apoptosis were detected through HE staining and TUNEL assay. Myelin sheath loss and nerve fiber damage were detected by LFB staining. Inflammatory factors, oxidative stress, and brain damage markers were detected through ELISA. The expression of apoptosis-related proteins and PI3K/PDK1/AKT signaling pathway related proteins were measured by western blot. The expressions of PI3K, PDK1, AKT, and MBP in paraventricular white matter cells were detected by immunofluorescence. Results Naomaitai treatment decreased neurological function score in rats with vascular dementia, ameliorated paraventricular white matter damage caused by long-term hypoxia, and hypoperfusion reduced the brain injury markers S-100β and NSE contents, suppressed inflammatory reaction and oxidative stress, reduced IL-1β, IL-6, TNF-α, and MDA contents, and remarkably increased IL-10 and SOD contents. TUNEL and western blot assay showed that Naomaitai treatment decreased neuronal cell apoptosis, increased Bcl-2 expression, and reduced caspase-3 and Bax expression. Furthermore, we found Naomaitai inhibited PI3K and PDK1 expression and activated phosphorylated AKT protein in rats with vascular dementia. However, the protective effect of Naomatai in rats with vascular dementia was inhibited, and expression of PI3K signaling pathway-related proteins was blocked after administration of PI3K inhibitor. Conclusion Naomaitai can ameliorate brain damage in rats with vascular dementia, inhibit neuronal apoptosis, and have anti-inflammatory and antioxidative stress effects, which may be regulated by the PI3K/PDK1/AKT signaling pathway.
Highlights
Vascular dementia (VD) is a severe cognitive impairment syndrome caused by long-term hypoxia and hypoperfusion in the brain [1]
The results revealed that PI3K, PDK1, and AKT expression increased in the white matter after model establishment in the VD group
Our results indicated that NMT could ameliorate hypoxia and ischemia in the white matter of VD rats, and the therapeutic effect may be associated with the inhibition of expression of the PI3K/PDK1/AKT signaling pathway
Summary
Vascular dementia (VD) is a severe cognitive impairment syndrome caused by long-term hypoxia and hypoperfusion in the brain [1]. Cerebrovascular diseases, such as ischemic stroke, hemorrhagic stroke, and cerebral ischemia and hypoxia, are the main clinical causes for VD [2]. The research showed that longterm hypoxia and hypoperfusion in the brain region caused by the damage to the paraventricular white matter is the main factor of VD [4]. The damaged areas showed pathological changes such as glial cell activation and proliferation [5]. Glial cell activation produced reactive oxygen species, which promoted the occurrence of oxidative stress [6]. Cytokine secretion stimulated inflammatory reaction and aggravated white matter damage [7]
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