缺血性中風中炎症動態與神經保護機制的整合：基於數值 模擬的治療策略研究

Abstract

缺血性中風的特徵是大腦血流（CBF）和氧分壓（𝑃𝑂2）的降低，這會導致顯著的神經損傷和神經炎症。中風發作時，身體會觸發由小膠質細胞介導的炎症反應，這些細胞會對周圍腦細胞釋放的病理信號作出反應。儘管這一過程可能加劇腦損傷，但同時也在腦部恢復過程中扮演著至關重要的角色。理解並調節這種雙重效應對改善中風後的治療結果至關重要。 本研究開發了一個數學模型來模擬神經保護劑和高壓氧治療（HBOT）在缺血性中風中的機制。該模型旨在確定HBOT是否能顯著改變炎症動態，從而增強神經保護作用。通過整合關鍵參數，本模型檢視了大腦血流、𝑃𝑂2 水平和小膠質細胞轉化之間的相互作用，以評估不同𝑃𝑂2輸入水平如何在不同的氧合條件下影響炎症和神經保護作用。 在穩態分析中，通過匹配不同參數，找到了在不同血流變化情境下最能提升𝑃𝑂2水平的最佳參數組合。隨後的模擬結果表明，𝑃𝑂2水平的變化可能會導致炎症軌跡和康復過程中可測量的差異。接下來，我們將模擬範圍擴展至空間層面，觀察在使用或不使用HBOT的情況下，氧氣在炎症區域的擴散情況。模擬結果顯示一致的趨勢，證實了模型的可靠性。 通過整合生理學和臨床參數，本研究提供了一個預測框架，有助於深入理解神經保護動態，並指導中風後治療的優化。研究結果預計將為臨床策略提供參考，並促進有效的神經保護干預的發展。

Ischaemic stroke, characterised by reduced cerebral blood flow (CBF) and oxygen partial pressure (𝑃𝑂2), results in significant neuronal damage and neuroinflammation. At the onset of stroke, the body triggers an inflammatory response mediated by microglia, which respond to pathological signals released by surrounding brain cells. While this response may potentially exacerbate brain injury, it also plays a crucial role in recovery. Understanding and modulating this dual effect is essential for improving post-stroke outcomes.

This study develops a novel mathematical model to simulate the mechanisms of neuroprotective agents and hyperbaric oxygen therapy (HBOT) in the context of ischaemic stroke. The model aims to determine whether HBOT can significantly alter inflammation dynamics, thereby enhancing neuroprotection. By integrating key parameters, the model examines the interactions between cerebral blood flow, 𝑃𝑂2 levels, and microglial transformation to assess how varying 𝑃𝑂2 input levels influence inflammation and neuroprotection under different oxygenation conditions.

In the steady-state analysis, we identified the optimal parameter combinations that best enhance 𝑃𝑂2 levels under various blood flow change scenarios. Subsequent simulation results suggest that variations in 𝑃𝑂2 levels may lead to measurable differences in inflammation trajectories and recovery processes. Next, we extended the simulation to the spatial level, observing how oxygen diffuses within the inflammation areas with or without HBOT. The simulation results showed consistent trends, confirming the reliability of the model.

By integrating physiological and clinical parameters, this study provides a predictive framework to deepen the understanding of neuroprotection dynamics and guide the optimisation of post-stroke treatments. The findings are expected to offer valuable insights for clinical strategies and contribute to the development of effective neuroprotective interventions.