Abstract
Objective The neuroinflammatory reaction activated after the activation of microglia plays a critical role in the pathological mechanism of early brain injury after subarachnoid hemorrhage. The inhibitory effect of Puerarin on inflammatory response plays a protective effect against various diseases. The present study mainly explored whether Puerarin alleviates the inflammation after SAH by inhibiting the Notchl pathway. Methods: Rat SAH model was induced by internal carotid artery puncture. The content of brain edema was evaluated and assessed. Evans blue staining was used to detect the degree of blood-brain barrier damage. FJC staining was used to assess neuronal apoptosis. Western blot method was employed to detect the expressions of Notchl receptor and downstream factors to clarify the protective effect and specific mechanism of Puerarin on brain tissue after SAH. Results: Puerarin can attenuate the brain edema and blood-brain barrier damage caused by early brain injury within 72 h after SAH, reduce the contents of Ibal and CD68 positive microglia. Intraventricular injection of Notchl receptor blockers and Notchl siRNA can inhibit the activation of Notchl pathway after SAH, mitigate brain tissue edema, blood-brain barrier damage, and neuronal apoptosis, as well as inhibit the activation of microglia and the release of inflammatory factors. Puerarin can inhibit the activation of Notchl receptor and downstream pathways, and simultaneously increase the content of Botch in brain tissue. Conclusion: Puerarin can inhibit the activation of Notchl receptor through Botch factor, thereby inhibiting the neuroinflammatory reaction mediated by Notchl pathway, and finally improve the early neurological dysfunction after SAH.
Highlights
Subarachnoid hemorrhage (SAH) refers to a pathological change caused by blood entering the subarachnoid space
The results showed that, after treatment with different concentrations of drugs, the Evans blue content in the lateral brain tissue after SAH were reduced, indicating that Puerarin has a certain protective effect on the blood brain barrier, see Figure 2
The results showed that Puerarin can reduce the number of FJC positive cells after SAH and increase the content of normal neuronal cell marker NeuN, proving that different concentrations of drugs can reduce the degenerative apoptosis of neuronal cells after SAH, see Figure 3
Summary
Subarachnoid hemorrhage (SAH) refers to a pathological change caused by blood entering the subarachnoid space. Spontaneous SAH is most commonly caused by bleeding from a ruptured intracranial aneurysm. The mortality rate of first-time bleeding is 40%, while the mortality rate of rebleeding is as high as 40-75%, seriously endangering human life and health, and causing a huge social burden (Minhas et al, 2019; Ballini et al, 2018; Fan et al, 2016). EBI refers to the pathophysiological process that occurs within 72 h after SAH. Due to the sharp increase of intracranial pressure and the decrease of cerebral perfusion pressure, blood cells and metabolites enter the subarachnoid space, producing cytotoxic reactions, causing depolarization of the cerebral cortex, oxidative stress, inflammation, apoptosis, autophagy and other cell metabolic response, eventually leading to nerve cell death, blood-brain barrier destruction, brain edema and neurological dysfunction. The complex signaling pathways and molecular mechanisms involved in EBI still need further research (Ferri et al, 2016)
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