2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38819Plasminogen activators (PAs) are serine proteases that convert the zymogen, plasminogen, into the active serine protease, plasmin. There are two types-tissue-type PA (tPA) and urokinase-type PA (uPA). PAs have been identified as a mediator of brain inflammatory reaction. This enzyme play an essential role in the breakdown of the extracellular matrix (ECM) macromolecules, blood-brain barrier (BBB) damage and induce neuro-inflammatory diseases. The level of PAs is measured in the CSF from patients with various meningitis including bacterial, viral or fungal meningitis. Our previous study showed that PAs are associated with eosinophilic meningitis and that the enzyme may be an useful marker for angiostrongyliasis meningitis. Neuroserpin (NS), a recently identified inhibitor of PAs, particularly, tissue-type plasminogen activator (tPA), is primarily localized to neurons within the central nervous system, where it is thought to regulate tPA activity. NS is also reported to limit both laminin degradation and microglial activation, two events known to worsen ischemic neuronal death. NS significantly reduces brain damages induced by late thrombolysis with tPA, an observation which was associated with a reduced BBB-leakage. Considering inhibiting serine proteases, NS could offer a new strategy for limit the pro-excitotoxic effects of tPA within the angiostrongyliasis meningitis. Here, we aimed at determining the mechanisms of NS protective BBB breakdown in angiostrongyliasis meningitis.血纖維蛋白酶原活化因子(plasminogen activators, PAs)是絲胺酸(serine)家族的蛋白酶，可將血纖維蛋白酶原(plasminogen)活化成血纖維蛋白酶(plasmin)，此活化因子可分為tissue-type plasminogen activator (tPA)和urokinase-type plasminogen (uPA)兩種，血纖維蛋白酶會分解細胞外質(extracellular matrix, ECM)，增加血腦障壁(blood-brain barrier, BBB)的通透性，媒介腦部的發炎反應，引起神經發炎。在細菌、病毒或黴菌引起的腦膜炎顯示腦脊髓液(cerebrospinal fluid, CSF) PAs增加。本實驗室先前的研究顯示PAs與嗜伊紅性腦膜炎(eosinophilic meningitis)有關，且可以做為廣東住血線蟲(Angiostrongylus cantonensis)引起腦膜炎的指標性酵素。Neuroserpin (NS)是PAs的抑制劑，特別是tissue-type plasminogen activator (tPA)，NS主要表現在中樞神經系統中可調控tPA的活性、減少lamin的降解及microglial的活性以減少神經細胞受損，在腦部受傷的情況下NS可以減少tPA的thrombolysis因此可減少BBB的損害。因此，本研究主要探討NS對於鼷鼠感染廣東住血線蟲所造的BBB損害的保護作用，進一步找出廣東住血線蟲感染時導致嗜伊紅性腦膜腦炎之致病機轉及治療機制，由此模式提供臨床上治療此症。廣東住血線蟲嗜伊紅性腦膜腦炎neuroserpin血液-中樞神經系統障壁血纖維蛋白?原活化因子Angiostrongylus cantonensisneuroserpinBBBplasminogen activatorsProject