Dobson Howard, Sharp Matthew MacGregor, Cumpsty Richard, Criswell Theodore P, Wellman Tyler, Finucane Ciara, Sullivan Jenna M, Weller Roy O, Verma Ajay, Carare Roxana O
inviCRO, Boston, U.S.A.
Department of Clinical Studies, University of Guelph, Ontario, Canada.
Clin Sci (Lond). 2017 Nov 13;131(22):2745-2752. doi: 10.1042/CS20171265. Print 2017 Nov 15.
Although there are no conventional lymphatic vessels in the brain, fluid and solutes drain along basement membranes (BMs) of cerebral capillaries and arteries towards the subarachnoid space and cervical lymph nodes. Convective influx/glymphatic entry of the cerebrospinal fluid (CSF) into the brain parenchyma occurs along the pial-glial BMs of arteries. This project tested the hypotheses that pial-glial BM of arteries are thicker in the midbrain, allowing more glymphatic entry of CSF. The MRI and PET images were obtained from a 4.2-year-old dog, whereas the post-mortem electron microscopy was performed in a 12-year-old dog. We demonstrated a significant increase in the thickness of the pial-glial BM in the midbrain compared with the same BM in different regions of the brain and an increase in the convective influx of fluid from the subarachnoid space. These results are highly significant for the intrathecal drug delivery into the brain, indicating that the midbrain is better equipped for convective influx/glymphatic entry of the CSF.
尽管大脑中没有传统的淋巴管，但液体和溶质会沿着脑毛细血管和动脉的基底膜（BMs）流向蛛网膜下腔和颈部淋巴结。脑脊液（CSF）通过对流流入/神经胶质淋巴系统进入脑实质，这一过程沿着动脉的软膜-胶质基底膜发生。本项目检验了以下假设：中脑动脉的软膜-胶质基底膜更厚，从而允许更多脑脊液通过神经胶质淋巴系统进入。MRI和PET图像取自一只4.2岁的狗，而尸检电子显微镜检查则在一只12岁的狗身上进行。我们证明，与大脑不同区域的相同基底膜相比，中脑软膜-胶质基底膜的厚度显著增加，并且从蛛网膜下腔的液体对流流入也增加。这些结果对于鞘内给药进入大脑具有高度重要意义，表明中脑在脑脊液的对流流入/神经胶质淋巴系统进入方面具有更好的条件。
