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Published on: May 6, 2016
An Intracisternal Rabbit Model Reveals Treponema pallidum Egress Across an Intact Blood-Brain Barrier
Shu-Hao Fan1,2,3, Lin Xie1,2,3, Yue Zhong1,2,3
1Center of Clinical Laboratory, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Background:
Treponema pallidum (T. pallidum), the causative agent of syphilis, can invade the central nervous system (CNS) during early infection. However, whether blood-brain barrier (BBB) disruption is required for spirochetal traversal remains unresolved.
Methods:
To determine whether T. pallidum can traverse the BBB without disrupting its integrity, we established an intracisternal (i.c.) rabbit model. Systemic serological responses and T. pallidum DNA in peripheral tissues were assessed as evidence of spirochetal egress from the CNS to the periphery. BBB integrity was monitored throughout by the albumin quotient (QAlb) -a validated BBB integrity marker -with reference intervals derived from 20 healthy rabbits.
Results:
The i.c. live T. pallidum group developed serological responses between day 7 and day 14, with kinetics similar to the intravenous live T. pallidum group. No responses occurred in the i.c. heat-inactivated T. pallidum or i.c. control groups. T. pallidum DNA was detected in the brain and peripheral tissues (kidney, liver, spleen) of all i.c. live T. pallidum rabbits, but not in other groups. Throughout the 63 days, QAlb values in all i.c. groups remained within normal reference intervals, with no significant differences among groups (P > 0.05).
Conclusion:
T. pallidum can disseminate from the CNS to peripheral tissues without disrupting BBB integrity, as evidenced by systemic seroconversion, peripheral T. pallidum DNA detection, and stable QAlb. This challenges the view that BBB disruption is required for spirochetal traversal and highlights non-disruptive egress pathways.
