[Astragalus polysaccharide protects against blood-brain barrier damage in MCAO rats by inhibiting P2X7R channel]
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Objective:
To investigate the protective effect of astragalus polysaccharide (APS) against blood-brain barrier in a rat model of middle cerebral artery occlusion (MCAO) and the role of P2X7R channel in the protective mechanism.
Methods:
In rat microglial cell models of oxygen and glucose deprivation (OGD) or ATP treatment, the formation of blood-brain barrier in vitro was assessed using the leak test, and the effect of APS on the permeability of the blood-brain barrier was determined using LC-MS. In 12 SD rats, MCAO model was established followed by treatment with intraperitoneal injection of normal saline (n= 6) or APS (45 mg/kg, n=6) for 3 consecutive days, with another 6 rats without MCAO receiving saline injections as the control group. The permeability of the blood-brain barrier of the rats was evaluated by determining Evans blue (EB) extravasation, and ATP content in the brain tissue was detected using ELISA; the expression levels of matrix metalloproteinase-9 (MMP-9) and P2X7R in the brain tissue were detected with Western blot.
Results:
In the in vitro cell model of OGD or ATP treatment, APS treatment obviously promoted the repair of blood-brain barrier integrity. In the rat models, the EB content in the brain tissue and the blood-brain barrier permeability increased significantly in MCAO+saline group and MCAO+APS group as compared with those in the control group (P < 0.01). Compared with saline treatment, APS treatment significantly decreased EB content in the brain tissue and improved the blood-brain barrier permeability in the MCAO rats (P < 0.05). MCAO caused a significant reduction of ATP content and obviously increased the expression levels of MMP-9 and P2X7R in the brain tissue of the rats (P < 0.01), and these changes were significantly alleviated after APS treatment (P < 0.01 or 0.05).
Conclusion:
APS can protect the brain tissue of MCAO rats by stabilizing the internal environment, down-regulating the expression of MMP-9 and improving the permeability of blood-brain barrier under cerebral ischemia and hypoxia, and its mechanism may involve the inhibition of P2X7R channel.
Insights
Astragalus polysaccharide (APS) protects the brain by improving blood-brain barrier integrity in rats with middle cerebral artery occlusion (MCAO). APS may work by inhibiting the P2X7R channel, reducing MMP-9 expression, and stabilizing the internal environment.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Context:
- The integrity of the blood-brain barrier (BBB) is crucial for brain function.
- Cerebral ischemia, such as that caused by middle cerebral artery occlusion (MCAO), severely compromises BBB integrity.
- Understanding protective mechanisms against BBB damage is vital for developing therapeutic strategies.
Purpose:
- To investigate the neuroprotective effects of astragalus polysaccharide (APS) on the blood-brain barrier (BBB) in a rat model of middle cerebral artery occlusion (MCAO).
- To elucidate the role of the P2X7 receptor (P2X7R) channel in the protective mechanism of APS against MCAO-induced BBB damage.
Summary:
- Astragalus polysaccharide (APS) treatment significantly improved blood-brain barrier (BBB) integrity in both in vitro microglial cell models and in vivo rat models of middle cerebral artery occlusion (MCAO).
- APS administration reduced Evans blue extravasation and improved BBB permeability in MCAO rats.
- APS treatment alleviated MCAO-induced decreases in ATP content and suppressed the upregulation of matrix metalloproteinase-9 (MMP-9) and P2X7 receptor (P2X7R) in brain tissue.
Impact:
- This study reveals a potential therapeutic role for APS in mitigating brain damage following ischemic stroke.
- The findings suggest that targeting the P2X7R channel could be a viable strategy for protecting the BBB during cerebral ischemia.
- APS demonstrates promise as a neuroprotective agent by stabilizing the internal environment and reducing inflammatory markers like MMP-9.
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