The cerebrospinal fluid: regulator of neurogenesis, behavior, and beyond - PubMed (original) (raw)

Review

The cerebrospinal fluid: regulator of neurogenesis, behavior, and beyond

Mauro W Zappaterra et al. Cell Mol Life Sci. 2012 Sep.

Abstract

The cerebrospinal fluid (CSF) has attracted renewed interest as an active signaling milieu that regulates brain development, homeostasis, and disease. Advances in proteomics research have enabled an improved characterization of the CSF from development through adulthood, and key neurogenic signaling pathways that are transmitted via the CSF are now being elucidated. Due to its immediate contact with neural stem cells in the developing and adult brain, the CSF's ability to swiftly distribute signals across vast distances in the central nervous system is opening avenues to novel and exciting therapeutic approaches. In this review, we will discuss the development of the choroid plexus-CSF system, and review the current literature on how the CSF actively regulates mammalian brain development, behavior, and responses to traumatic brain injury.

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Figures

Fig. 1

Fig. 1

Coronal section of the human embryonic brain at gestational week 9. Left panel At gestational week 9 in the human embryo, the telencephalic choroid plexus occupies a large portion of the lateral ventricle. The choroid-plexus-secreted CSF in the lateral ventricles bathes the cortical neuroepithelium, thereby regulating neurogenesis and the formation of the cortical plate. Right panel a more posterior view of the developing human embryo at gestational week 9 shows that the lateral ventricle continues to be filled by the choroid plexus. The fourth ventricle choroid plexus is observed to extend along the length of the fourth ventricle. Asterisks denote third ventricle choroid plexus. ChP choroid plexus; LV lateral ventricle; NEP neuroepithelium; Tel telencephalon; Rhomb rhombencephalon; V ventricle. Reprinted with permission from the authors, Bayer SA, Altman J [10]

Fig. 2

Fig. 2

Sagittal schematic of CSF flow in the mature cerebroventricular system. CSF is produced primarily by the choroid plexus, which is located in each ventricle in the brain. CSF flows from the lateral ventricles, via the foramen of Monro, to the third ventricle, and then through the cerebral aqueduct/aqueduct of Sylvius to the fourth ventricle. Upon leaving the fourth ventricle, the CSF flows down the spinal cord and fills the subarachnoid space surrounding the brain. It is ultimately resorbed into the venous circulation by arachnoid villi

Fig. 3

Fig. 3

Coronal schematic of choroid plexus-secreted factors distributed in the CSF during embryonic cortical development. IGF2 (represented by purple spheres) and other factors secreted by the choroid plexus are delivered to target cells on the apical, ventricular surface of the developing cerebral cortex

Fig. 4

Fig. 4

Schematic illustrating brain states and associated factors distributed in the CSF. Different brain/body states including sleep/wake, appetite, and brain injury and repair have been linked with the presence of distinct factors in the CSF. In the case of brain injury and repair, most of the factors listed have been introduced intraventricularly into injury models, where they were reported to have beneficial effects on recovery from injury. The primary source and mode of action for many CSF factors remain to be elucidated

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