The choroid plexus (CP) forming the blood–cerebrospinal fluid (B-CSF) barrier is among the least studied structures of the central nervous system (CNS) despite its clinical importance. The CP is an epithelio-endothelial convolute comprising a highly vascularized stroma with fenestrated capillaries and a continuous lining of epithelial cells joined by apical tight junctions (TJs) that are crucial in forming the B-CSF barrier. Integrity of the CP is critical for maintaining brain homeostasis and B-CSF barrier permeability. Recent experimental and clinical research has uncovered the significance of the CP in the pathophysiology of various diseases affecting the CNS. The CP is involved in penetration of various pathogens into the CNS, as well as the development of neurodegenerative (e.g., Alzheimer´s disease) and autoimmune diseases (e.g., multiple sclerosis). Moreover, the CP was shown to be important for restoring brain homeostasis following stroke and trauma. In addition, new diagnostic methods and treatment of CP papilloma and carcinoma have recently been developed. This review describes and summarizes the current state of knowledge with regard to the roles of the CP and B-CSF barrier in the pathophysiology of various types of CNS diseases and sets up the foundation for further avenues of research.

Brain metastases (BMs) are the most common intracranial tumors in adults and occur 3–10 times more frequently than primary brain tumors. Despite intensive multimodal therapies, including resection, radiotherapy, and chemotherapy, BMs are associated with poor prognosis and remain challenging to treat. BMs predominantly originate from primary lung (20–56%), breast (5–20%), and melanoma (7–16%) tumors, although they can arise from other cancer types less frequently. The metastatic cascade is a multistep process involving local invasion, intravasation into the bloodstream or lymphatic system, extravasation into normal tissue, and colonization of the distal site. After reaching the brain, circulating tumor cells (CTCs) breach the blood–brain barrier (BBB). The selective permeability of the BBB poses a significant challenge for therapeutic compounds, limiting the treatment efficacy of BMs. Understanding the mechanisms of tumor cell interactions with the BBB is crucial for the development of effective treatments. This review provides an in-depth analysis of the brain barriers, including the BBB, blood-spinal cord barrier, blood-meningeal barrier, blood-arachnoid barrier, and blood-cerebrospinal fluid barrier. It explores the molecular and cellular components of these barriers and their roles in brain metastasis, highlighting the importance of this knowledge for identifying druggable targets to prevent or limit BM formation.

Subarachnoid hemorrhage (SAH) is a specific form of hemorrhagic stroke that frequently causes intracranial hypertension. The choroid plexus (CP) of the brain ventricles is responsible for producing cerebrospinal fluid and forms the blood – cerebrospinal fluid barrier. The aim of the current study was to determine whether SAH induces an immune cell reaction in the CP and whether the resulting increase in intracranial pressure (ICP) itself can lead to cellular changes in the CP. SAH was induced by injecting non-heparinized autologous blood to the cisterna magna. Artificial cerebrospinal fluid (ACSF) instead of blood was used to assess influence of increased ICP alone. SAH and ACSF animals were left to survive for 1, 3, and 7 days. SAH induced significantly increased numbers of M1 (ED1+, CCR7+) and M2 (ED2+, CD206+) macrophages as well as MHC-II+ antigen presenting cells (APC) compared to naïve and ACSF animals. Increased numbers of ED1+ macrophages and APC were found in the CP only 3 and 7 days after ACSF injection, while ED2+ macrophage number did not increase. CD3+ T cells were not found in any of the animals. Following SAH, proliferation activity in the CP gradually increased over time while ACSF application induced higher cellular proliferation only 1 and 3 days after injection. Our results show that SAH induces an immune reaction in the CP resulting in an increase in the number of several macrophage types in the epiplexus position. Moreover, we also found that increased ICP due to ACSF application induced both an immune reaction and increased proliferation of epiplexus cells in the CP. These findings indicate that increased ICP, and not just blood, contributes to cellular changes in the CP following SAH.

Glioblastoma (GBM) is regarded as an aggressive brain tumor that rarely develops extracranial metastases. Despite well-investigated molecular alterations in GBM, there is a limited understanding of these associated with the metastatic potential. We herein present a case report of a 43-year-old woman with frontal GBM with primitive neuronal component who underwent gross total resection followed by chemoradiation. Five months after surgery, the patient was diagnosed with an intraspinal GBM metastasis. Next-generation sequencing analysis of both the primary and metastatic GBM tissues was performed using the Illumina TruSight Tumor 170 assay. The number of single nucleotide variants observed in the metastatic sample was more than two times higher. Mutations in TP53, PTEN, and RB1 found in the primary and metastatic tissue samples indicated the mesenchymal molecular GBM subtype. Among others, there were two inactivating mutations (Arg1026Ile, Trp1831Ter) detected in the NF1 gene, two novel NOTCH3 variants of unknown significance predicted to be damaging (Pro1505Thr, Cys1099Tyr), one novel ARID1A variant of unknown significance (Arg1046Ser), and one gene fusion of unknown significance, EIF2B5-KIF5B, in the metastatic sample. Based on the literature evidence, the alterations of NF1, NOTCH3, and ARID1A could explain, at least in part, the acquired invasiveness and metastatic potential in this particular GBM case.