Choroid plexus perfusion and intracranial cerebrospinal fluid changes after angiogenesis

Abstract

Recent studies have provided evidence that cortical brain ischemia may influence choroid plexus function, and such communication may be mediated by either traditional CSF circulation pathways and/or a possible glymphatic pathway. Here we investigated the hypothesis that improvements in arterial health following neoangiogenesis alter (i) intracranial CSF volume and (ii) choroid plexus perfusion in humans. CSF and tissue volume measurements were obtained from T₁-weighted MRI, and cortical and choroid plexus perfusion were obtained from perfusion-weighted arterial spin labeling MRI, in patients with non-atherosclerotic intracranial stenosis (e.g. Moyamoya). Measurements were repeated after indirect surgical revascularization, which elicits cortical neoangiogenesis near the revascularization site (n = 23; age = 41.8 ± 13.4 years), or in a cohort of participants at two time points without interval surgeries (n = 10; age = 41.7 ± 10.7 years). Regression analyses were used to evaluate dependence of perfusion and volume on state (time 1 vs. 2). Post-surgery, neither CSF nor tissue volumes changed significantly. In surgical patients, cortical perfusion increased and choroid plexus perfusion decreased after surgery; in participants without surgeries, cortical perfusion reduced and choroid plexus perfusion increased between time points. Findings are discussed in the context of a homeostatic mechanism, whereby arterial health, paravascular flow, and/or ischemia can affect choroid plexus perfusion.

Keywords: Cerebrospinal fluid; arterial spin labeling; choroid plexus; glymphatic; ischemia; perfusion.

Figure 1.

Components of traditional and novel CSF circulation pathways. (a) Sagittal T₁-weighted MRI showing the traditional cerebrospinal fluid (CSF) flow pathway consisting of (1) choroid plexus, which produces CSF; (2) cerebral aqueduct through which CSF flows from third to fourth ventricles, after which CSF circulates through arachnoid space where it can be (3) removed through arachnoid projections into the venous system. This system has been adapted to include (b) a glymphatic pathway, in which CSF influx occurs along periarterial spaces. Aquaporin-4 (AQP4) channels (pink) mediate the flow of fluid from the paravascular arterial space to interstitial space. Convection currents from astrocytes allow for net fluid flow through interstitial space and via AQP4 channels fluid flows into venous paravascular space. Net fluid flow reaches the cervical lymph nodes (a; 4) through small CNS lymphatic channels.

Figure 2.

Indirect surgical revascularization. A 32-year-female patient scanned before and after an encephaloduroarteriosynangiosis indirect surgical revascularization. (a) Anterior–posterior oblique projection following injection of the left internal carotid artery shows clear middle cerebral artery stenosis (white arrow) and limited middle cerebral artery territory filling. (b) Post-revascularization and following left external carotid artery injection, neoangiogenesis and increased collateralization (black arrows) are apparent in both the early (left) and late (right) arterial lateral projections. (c) Shows the pretreatment lateral projection following left internal carotid artery injection in late arterial phase, which shows large areas of poor arterial supply to portions of the right middle cerebral artery distribution and (d) The lateral correlate of panel (b).

Figure 3.

Group-level relationships between study parameters. Cerebrospinal fluid (CSF) volume, cortical perfusion near the revascularization site, and choroid plexus perfusion in (a) non-surgical participants scanned at two time points and (b) surgical participants scanned before and after revascularization. In both groups, CSF volume does not change significantly. However, in the non-surgical group (a), cortical perfusion decreases slightly and choroid plexus perfusion increases slightly. Alternatively, in the surgical group (b), the cortical perfusion increases slightly, consistent with the effect of revascularization, and the choroid plexus perfusion decreases. Error bars denote standard deviation and summarize the large inter-subject variation, consistent with known, varied responses of surgical revascularization and the heterogeneous and varied nature of the disease. Significance of these findings are reported in the regression analysis in Table 2, in which a strong trend (*p = 0.05) is found for the cortical perfusion change between times for the different groups, and a significant (**p = 0.035) choroid plexus perfusion change is found between times for the different groups, after accounting for interval scan duration.

Figure 4.

Longitudinal cerebral blood flow changes in two representative patients. (a) A T₁-weighted atlas at the approximate location of the shown blood flow maps. (b) A patient with moyamoya (age = 58 years; sex = female) scanned at an interval of 72 days with no interim surgery. The images suggest subtle reductions in cortical perfusion and slight increases in choroid plexus perfusion (green arrow). (c) A patient with moyamoya with interval surgery (age = 31 years; sex = female) scanned 72 days after left-sided encephaloduroarteriomyosynangiosis. Increases in cortical perfusion are observed near the revascularization site (yellow arrow), whereas bilateral decreases in choroid plexus perfusion are observed.

Figure 5.

Hypothesized feedback mechanisms between cortical arterial health and choroid plexus perfusion. Indirect surgical revascularization on average was found to lead to increases in cortical perfusion and reductions in choroid plexus perfusion in patients with intracranial arterial steno-occlusive disease. Three possible pathways that could describe the choroid plexus perfusion reduction are proposed, which rely on (a) glymphatic, (b) ischemic biochemical feedback, and/or (c) changes in blood vasculature. It should be noted that the ischemic biochemical feedback and glymphatic pathways may share overlapping mechanisms, depending on how biochemical stressors are circulated to CSF and choroid plexus. Additional information on each pathway is provided in the Discussion.