先前研究證實腸病毒71型可經由腸道擴散到血液中，並在周邊神經系統複製而傳播到中樞神經系統。然而腸病毒71型的感染是否會造成血腦障壁通透性的上升而入侵中樞神經目前仍不清楚。本論文利用可強烈結合血液中血漿蛋白的伊凡藍氏染劑評估感染腸病毒71型後其血腦障壁通透性的改變。結果顯示小鼠在口服感染腸病毒71型24小時後出現病毒血症，然而此時腦部尚無病毒出現，表示腸病毒71型感染後的病毒血症無法立即引發嚴重的腦部感染。而在感染後30、60及72小時，血腦障壁通透性有明顯上升，同時在30小時延腦出現少量病毒，證實血腦障壁通透性上升與病毒入侵腦部有關。脊髓方面，在感染48小時後有病毒出現，病毒首先出現在腰椎及胸椎部分，頸椎則在感染72小時後出現病毒，顯示腸病毒71型可經由周邊神經傳播到中樞神經系統。此外我們發現在腸病毒71型感染後所誘發的細胞激素，如TNF-alpha及IL-10，與血腦障壁通透性之改變也可能相關。總括而言，腸病毒71型侵犯神經中樞的途徑除了由周邊神經蔓延到中樞神經外，也可能通過血腦障壁而侵入腦部。

Previous study in our laboratory demonstrated that enterovirus 71 (EV71) possesses strong neurotropism and that EV71 might transmit with fast axonal transport in neuron cells in mice. However, whether EV71 could invade the central nervous system through circulation by alterating the permeability of blood-brain barrier (BBB) is not known. In this study, we used Evans blue dye, which would form an insoluble complex after binding with serum albumin to evaluate the permeability of BBB after EV71 infection. Our results showed there was a viremia as early as 24 hours after oral inoculation of EV71 without detectable infectious viruses in brain tissues. The BBB permeability was increased at 30, 60, and 72 hours post-inoculation. Coincidentally, a small amount of viruses could be detected in medulla at 30 hours post-inoculation without significantly increase followed time. EV71 was first detected in lumbar and thoracic sections of the spinal cord at 48 hours post-inoculation with a gradual increase in titer from the lower to the upper sections. Viruses appeared in cervical section of the spinal cord at 72 hours post-inoculation. EV71 infection induced an increase in TNF-alpha and IL-10 systemically and locally in brain tissues. Collectively, retrograde axonal transport as well as viremia may responsible for the transport of EV71 to the brain.

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