Fang Wei1, Cui Zhang1, Rong Xue1, Lidong Shan1, Shan Gong1, Guoqing Wang1, Jin Tao1, Guangyin Xu2, Guoxing Zhang1, Linhui Wang3. 1. Department of Physiology and Neurobiology, Medical College of Soochow University, 199 Ren-Ai Road, Suzhou 215123, PR China. 2. Institute of Neuroscience, Soochow University, 199 Ren-Ai Road, Suzhou 215123, PR China. 3. Department of Physiology and Neurobiology, Medical College of Soochow University, 199 Ren-Ai Road, Suzhou 215123, PR China. Electronic address: wanglinhui@suda.edu.cn.
Abstract
AIMS: It has been proved that cerebrospinal fluid (CSF) in the subarachnoid space could reenter the brain parenchyma via the perivascular space. The present study was designed to explore the pathway of subarachnoid CSF flux into the spinal cord and the potential role of aquaporin-4 (AQP4) in this process. MAIN METHODS: Fluorescently tagged cadaverine, for the first time, was used to study CSF movement in mice. Following intracisternal infusion of CSF tracers, the cervical spinal cord was sliced and prepared for fluorescence imaging. Some sections were subject with immunostaining in order to observe tracer distribution and AQP4 expression. KEY FINDINGS: Fluorescently tagged cadaverine rapidly entered the spinal cord. Tracer influx into the spinal parenchyma was time dependent. At 10min post-infusion, cadaverine was largely distributed in the superficial tissue adjacent to the pial surface. At 70min post-infusion, cadaverine was distributed in the whole cord and especially concentrated in the gray matter. Furthermore, fluorescent tracer could enter the spinal parenchyma either along the perivascular space or across the pial surface. AQP4 was observed highly expressed in the astrocytic endfeet surrounding blood vessels and the pial surface. Blocking AQP4 by its specific inhibitor TGN-020 strikingly reduced the inflow of CSF tracers into the spinal cord. SIGNIFICANCE: Subarachnoid CSF could flow into the spinal cord along the perivascular space or across the pial surface, in which AQP4 is involved. Our observation provides a basis for the study on CSF movement in the spinal cord when some neurological diseases occur.
AIMS: It has been proved that cerebrospinal fluid (CSF) in the subarachnoid space could reenter the brain parenchyma via the perivascular space. The present study was designed to explore the pathway of subarachnoid CSF flux into the spinal cord and the potential role of aquaporin-4 (AQP4) in this process. MAIN METHODS: Fluorescently tagged cadaverine, for the first time, was used to study CSF movement in mice. Following intracisternal infusion of CSF tracers, the cervical spinal cord was sliced and prepared for fluorescence imaging. Some sections were subject with immunostaining in order to observe tracer distribution and AQP4 expression. KEY FINDINGS: Fluorescently tagged cadaverine rapidly entered the spinal cord. Tracer influx into the spinal parenchyma was time dependent. At 10min post-infusion, cadaverine was largely distributed in the superficial tissue adjacent to the pial surface. At 70min post-infusion, cadaverine was distributed in the whole cord and especially concentrated in the gray matter. Furthermore, fluorescent tracer could enter the spinal parenchyma either along the perivascular space or across the pial surface. AQP4 was observed highly expressed in the astrocytic endfeet surrounding blood vessels and the pial surface. Blocking AQP4 by its specific inhibitor TGN-020 strikingly reduced the inflow of CSF tracers into the spinal cord. SIGNIFICANCE: Subarachnoid CSF could flow into the spinal cord along the perivascular space or across the pial surface, in which AQP4 is involved. Our observation provides a basis for the study on CSF movement in the spinal cord when some neurological diseases occur.
Authors: Shinuo Liu; Lynne E Bilston; Neftali Flores Rodriguez; Courtney Wright; Simon McMullan; Robert Lloyd; Marcus A Stoodley; Sarah J Hemley Journal: Fluids Barriers CNS Date: 2022-02-08
Authors: Xiaowei Wang; Nanhong Lou; Allison Eberhardt; Yujia Yang; Peter Kusk; Qiwu Xu; Benjamin Förstera; Sisi Peng; Meng Shi; Antonio Ladrón-de-Guevara; Christine Delle; Björn Sigurdsson; Anna L R Xavier; Ali Ertürk; Richard T Libby; Lu Chen; Alexander S Thrane; Maiken Nedergaard Journal: Sci Transl Med Date: 2020-03-25 Impact factor: 17.956