The Role of the Choroid Plexus in Neutrophil Invasion after Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) frequently results in neuroinflammation, which includes the invasion of neutrophils. After TBI, neutrophils infiltrate the choroid plexus (CP), a site of the blood-cerebrospinal fluid (CSF) barrier (BCSFB), and accumulate in the CSF space near the injury, from where these inflammatory cells may migrate to brain parenchyma. We have hypothesized that the CP functions as an entry point for neutrophils to invade the injured brain. Using the controlled cortical impact model of TBI in rats and an in vitro model of the BCSFB, we show that the CP produces CXC chemokines, such as cytokine-induced neutrophil chemoattractant (CINC)-1 or CXCL1, CINC-2a or CXCL3, and CINC-3 or CXCL2. These chemokines are secreted both apically and basolaterally from the choroidal epithelium, a prerequisite for neutrophil migration across epithelial barriers. Consistent with these findings, we also provide electron microscopic evidence that neutrophils infiltrate the choroidal stroma and subsequently reach the intercellular space between choroidal epithelial cells. This is the first detailed analysis of the BCSFB function related to neutrophil trafficking. Our observations support the role of this barrier in posttraumatic neutrophil invasion.

Posttraumatic Invasion of Monocytes across the Blood—Cerebrospinal Fluid Barrier

“…The type I IL-1 receptor has previously been identified by in situ hybridization to be expressed in the CP (Ericsson et al, 1995), and we have confirmed its expression on epithelial monolayers (Szmydynger-Chodobska et al, 2009).…”

“…Similar to the movement of neutrophils (Szmydynger-Chodobska et al, 2009), the migration of monocytes across the BCSFB appeared to involve the paracellular pathway. The movement of monocytes along the paracellular pathway was frequently associated with the widening of space between invading inflammatory cells and the adjacent epithelial cells (see Figures 4H and 4I), a phenomenon not observed for migrating neutrophils (Szmydynger-Chodobska et al, 2009). Interestingly, monocytes were sometimes found to invade the ipsilateral CP in tandem with neutrophils (see Figure 4J).…”

“…Immunohistochemical procedures were performed as previously described (Szmydynger-Chodobska et al, 2009, 2010. Rats (2 to 4 animals per group) were reanesthetized with pentobarbital sodium and were perfused transcardially with ice-cold 0.9% NaCl, followed by ice-cold 4% paraformaldehyde in 0.05 mol/L PBS (phosphatebuffered saline), pH 7.4.…”

“…The BCSFB is formed by a single layer of epithelial cells enclosing blood microvessels in the highly vascularized choroid plexus (CP), a tissue located in all four cerebral ventricles (Strazielle and Ghersi-Egea, 2000). We have previously shown that the choroidal epithelium has the ability to produce neutrophil chemoattractants and provided electron microscopic evidence for neutrophil trafficking across the BCSFB (Szmydynger-Chodobska et al, 2009). However, investigations have not determined whether the BCSFB also has a role in the recruitment of monocytes to the injured brain.…”

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

“…5c). Indeed, the choroid plexus transcriptome, proteome, and secretome are dynamic and rapidly change in response to external cues, such as inflammation [89,155]. Choroid plexus epithelial cells have many villi, providing a large surface area for detection of signals in the CSF.…”