Choroid plexus CCL2‒CCR2 signaling orchestrates macrophage recruitment and cerebrospinal fluid hypersecretion in hydrocephalus

The choroid plexus(ChP)serves as the principal origin of cerebrospinal fluid(CSF).CSF hypersecretion due to ChP inflammation has emerged as an important pathogenesis of hydrocephalus recently.Nevertheless,the precise mechanisms of ChP inflammation and the ensuing CSF hypersecretion in hydrocephalus remain ill-defined.In the present study,we elucidate the critical role of macrophages in the pathogenesis of ChP inflammation.Specifically,we identify the chemokine CCL2,released by ChP epithelial cells,recruits CCR2+monocytes to the ChP thereby inciting hydrocephalus pathogenesis.The accumulated ChP macrophages increase the inflammation in ChP epithelial cells through TNF-α/TNFR1/NF-κB signaling cascade,thereby leading to CSF hypersecretion.Strikingly,augmentation of ChP‒CCL2 using an adeno-associated viral approach(AAV)exacerbates macrophage recruitment,activation,and ventriculomegaly in rat PHH models.Systemic application of Bindarit,a specific CCL2 inhibitor,significantly inhibits ChP macrophage infiltration and activation and reduces CSF secretion rate.Furthermore,the administration of CCR2 antagonist(INCB 3284)reduces ChP macrophage accumulation and ventriculomegaly.This study not only unveils the ChP CCL2‒CCR2 signaling in the pathophysiology of hydrocephalus but also unveils Bindarit as a promising therapeutic choice for the management of posthemorrhagic hydrocephalus.

Exposing vertebral artery from lateral to medial under the guide of peri-vertebral artery fat pad in far lateral approach

Far lateral approach(FLA),together with its modified approaches,is a fundamental surgical approach for surgical resection of lesions located at the ventral or ventrolateral side of the foramen magnum.[1,2,3,4,5]The key procedure in FLA is exposing the vertebral artery(VA)especially the V3 segment.[1,5,6]When performing an FLA,most neurosurgeons choose to expose the suboccipital triangle(formed by the rectus capitis posterior major,the superior oblique,and the inferior oblique)as a key anatomical landmark initially and then expose the V3 segment.[1,2,5,6,7]However,on the one hand,this muscular anatomical landmarks-suboccipital triangle varies in depth,morphology,and location in different patients,which increases the risk of VA injury during surgery.[3]On the other hand,this procedure could lead to exposing difficulty due to the obstruction of overlying layers of muscles and the distribution of blood vessels,which could prolong the time for craniotomy fairly.The course of VA could vary,such as looping backward and bulge posteriorly between the lips of the suboccipital triangle,where it could be damaged if one expects it to be found in the depth of the suboccipital triangle.[3]Thus,neurosurgeons have the potential for VA injury and a rather prolonged time to successfully expose VA.