Taking a Closer Look at the Ventricular System
Post by Lani Cupo
What is the ventricular system?
Ventricles are cavities deep within the brain, filled with cerebrospinal fluid (CSF). The presence of ventricles in the brain was first recorded in the 3rd century BCE by Greek physicians Herophilos and Erasistratus (Mortazavi et al., 2013). Their belief that core functions of the brain were produced by the ventricles persisted into the 16th century when Leonardo da Vinci performed the first ventriculography by injecting molten wax into the ventricles of an ox (Mortazavi et al., 2013). The dominant theory at the time attributed individual cognitive functions to the three identified ventricles: imagination, reasoning, and memory, respectively (Mortazavi et al., 2013; da Mota Gomes, 2020). Over centuries, the idea that the ventricles were the seat of the soul was abandoned, but the ventricular system is still of great interest to neuroscientists and neurologists today.
In human brains, the ventricular system is comprised of four CSF-containing cavities, with channels between them. These include two lateral ventricles (one in each hemisphere of the brain), the third ventricle (located at the center of the head), and the fourth ventricle (located between the brainstem and the cerebellum). The CSF that fills the ventricles is produced by the choroid plexus, a network of specialized cells that line the ventricles. Three layers of cells, or meninges, line the ventricles, and in many areas, these provide a barrier between the ventricles and the vasculature called the blood-brain barrier (BBB), while in some regions of the third and fourth ventricles, this barrier is ineffective or entirely absent, allowing free communication between the ventricles and the bloodstream (Mortazavi et al., 2013).
What does the ventricular system do?
The ventricular system fulfills several important roles in the brain. Much of its function resembles that of the hematopoietic circulatory system (responsible for producing and transporting blood cells), including transporting nutrients and waste. It also protects the brain against physical trauma and plays an important role in brain development (Lowery et al., 2010; Segal et al., 2001).
The brain, unlike other organs, lacks a lymphatic drainage system to remove waste that accumulates as a result of cellular metabolism (Segal et al., 2001). Instead, waste slowly drains into the CSF through the ventricles, and eventually into the vasculature to be processed elsewhere in the body. In parallel, nutrients essential for proper brain function like ascorbate, vitamin B12, and thymidine can only enter the brain through the CSF (Segal et al., 2001). Thus, the ventricles help to maintain homeostasis in the brain. CSF provides protection to the brain. Not only does it help cushion blows, it also reduces the weight of the brain (from ~1500g to 50g), decreasing pressure on sensitive structures at the base of the brain (Segal et al., 2001).
Finally, the ventricles are critically involved in neurodevelopment. The early stages of the ventricles are formed in the first month of human development, when the layer of cells that becomes the brain folds, creating a tube that will go on to form the brain and spinal cord (Lowery et al., 2010). The regions of tissue surrounding the ventricles are the birthplace of cortical neurons (Duy et al., 2021). Stem cells located adjacent to ventricles divide - some becoming neurons - and then migrate away from the ventricles to form the layers of the cortex (Duy et al., 2021). There is also evidence that the choroid plexus may regulate neural stem cell behavior, but this topic requires further investigation at stages across the developmental process (Bitanihirwe et al., 2022).
How can we study the ventricles?
Since da Vinci injected wax into the ventricles of the ox, there have been major developments in how scientists study the ventricles. One of the main techniques used to study ventricular anatomy is neuroimaging. Magnetic resonance imaging (MRI) can be used to accurately measure the volume of ventricles across the lifespan. In human fetuses, the size of the lateral ventricle is most commonly first measured with ultrasound (Alluhaybi et al., 2022). A lumbar puncture can also be conducted to extract CSF and measure levels of proteins, sugars, and cells (Hrishi et al., 2019). Finally, the pressure within the ventricles can be monitored with a probe inserted into the skull. This is especially useful in studying pathologies of the ventricles.
What can go wrong with the ventricles?
Enlarged ventricles (also known as ventriculomegaly) have been recorded in both neurodevelopmental and neurodegenerative disorders. Hydrocephalus is a neurological disorder characterized by ventriculomegaly. In newborns, it can arise after an infection or bleeding in the brain, however, sometimes there is no known cause (Duy et al., 2021). CSF can accumulate in the brain, causing an enlargement of ventricles that can push and squeeze brain tissue and increase pressure within the skull. In these cases, surgery can remove excess CSF to decrease the pressure, which can help rescue some of the poor cognitive outcomes in children. Unfortunately, some cases of ventriculomegaly occur without any increased pressure, and in these cases diverting CSF does not seem to rescue downstream effects (Duy et al., 2021).
In contrast, ventriculomegaly in neurodegenerative disorders, such as Alzheimer’s Disease, occurs passively as the brain tissue atrophies and CSF begins to take up space where the tissue degrades (Apostolova et al., 2013). While there is variance in ventricular volume in the healthy adult population, enlarged ventricles have also been associated with various neuropsychiatric disorders, including Schizophrenia, bipolar disorder, and depression.
What is still unknown about the ventricles?
The brain’s ventricles have been investigated for centuries, but there are still many open questions about their function and role in development and degeneration. For example, how CSF content may impact behavior or mood is not well understood, with little information present in the scientific literature (Orts-Del’Immagine et al., 2017). Further, we need to understand how fluid moves between the blood and CSF, and how fluid buildup occurs in different types of hydrocephaly. Treatments for hydrocephaly are also lacking, and more research is needed to develop therapies. There’s an opportunity to better understand the choroid plexus, it’s role in neurodevelopment, and how hormones regulate the secretion of CSF that influences brain function. Lastly, the blood-brain barrier is a key area to focus to learn more about in the development of therapies that can be administered through the CSF and absorbed into the brain. Even as neuroscientists uncover mysteries related to the tissues of the brain, future studies may also shed light on the negative spaces between tissue, contributing to a deeper understanding of the entire organ.
References +
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Apostolova LG, Babakchanian S, Hwang KS, Green AE, Zlatev D, Chou Y-Y, et al. Ventricular enlargement and its clinical correlates in the imaging cohort from the ADCS MCI donepezil/vitamin E study. Alzheimer Dis Assoc Disord. 2013;27: 174–181.
Hrishi AP, Sethuraman M. Cerebrospinal Fluid (CSF) Analysis and Interpretation in Neurocritical Care for Acute Neurological Conditions. Indian J Crit Care Med. 2019;23: S115–S119.
Alluhaybi AA, Altuhaini K, Ahmad M. Fetal Ventriculomegaly: A Review of Literature. Cureus. 2022;14: e22352.
Bitanihirwe BKY, Lizano P, Woo T-UW. Deconstructing the functional neuroanatomy of the choroid plexus: an ontogenetic perspective for studying neurodevelopmental and neuropsychiatric disorders. Mol Psychiatry. 2022;27: 3573–3582.
Lowery LA, Sive H. Totally tubular: the mystery behind function and origin of the brain ventricular system. Bioessays. 2009;31: 446–458.
da Mota Gomes M. From the wax cast of brain ventricles (1508-9) by Leonardo da Vinci to air cast ventriculography (1918) by Walter E. Dandy. Rev Neurol. 2020;176: 393–396.
Mortazavi MM, Adeeb N, Griessenauer CJ, Sheikh H, Shahidi S, Tubbs RI, et al. The ventricular system of the brain: a comprehensive review of its history, anatomy, histology, embryology, and surgical considerations. Childs Nerv Syst. 2014;30: 19–35.
Duy PQ, Rakic P, Alper SL, Butler WE, Walsh CA, Sestan N, et al. Brain ventricles as windows into brain development and disease. Neuron. 2022;110: 12–15.
