The glia limitans, or the glial limiting membrane, is a thin barrier of astrocyte foot processes associated with the parenchymal basal lamina surrounding the brain and spinal cord.

The glia limitans also plays an important role in regulating the movement of small molecules and cells into the brain tissue by working in concert with other components of the central nervous system (CNS) such as the blood–brain barrier (BBB).

The glia limitans perivascularis abuts the perivascular space surrounding the parenchymal blood vessels and functions as a supportive constituent of the blood–brain barrier.

These endothelial cells contain highly impermeable tight junctions that cause the blood vessels of the brain to exhibit none of the “leakiness” found in arteries and veins elsewhere in the body.

[5] Through both in vivo and in vitro experiments the astrocytic foot processes of the glia limitans were shown to induce the formation of the tight junctions of the endothelial cells during brain development.

[1] The development of the long astrocyte cellular processes that are integral to the glia limitans structure has been linked to the presence of meningeal cells in the pia mater.

Artificially induced destruction of meningeal cells during CNS development have been found to result in the alteration of subpial extracellular matrix and a disruption of the glia limitans.

Breaches in the glia limitans-basal lamina complex have been associated with Fukuyama-type congenital muscular dystrophy (FCMD), which is thought to be the result of micropolygyri, or small protrusions of nervous tissue.

Mutations in the fukutin protein lead to a depressed level of its expression in the brain and spinal cord of neonatal subjects, which in turn has been found to contribute to the weakening of the structural integrity of the glia limitans.

[11] It has been demonstrated that the clinical signs of experimental autoimmune encephalomyelitis (EAE) are only evident after the penetration of inflammatory cells across the glia limitans and upon entrance into the CNS parenchyma.

However, they do have a sheath of perineurial glial cells that envelops the nervous system and exhibit the same tight occluding junctions that are induced by the glia limitans in humans.

In addition to protection from the blood, these barriers are thought to exhibit local control of the microenvironment around specific neuron groups, a function required for complex nervous systems.

Studies on these animals have revealed that the thickness of the glia limitans not only varies greatly among different species, but also within different regions of the central nervous system of the same organism.

They used advanced imaging methods to explain that the ion channels seen in glial cells did not contribute to action potentials but rather allowed the glia to determine the level of neuronal activity within proximity.

Additionally, neurons were found to release chemical messengers in extrasynaptic regions, suggesting that the neuron-glial relationship includes functions beyond synaptic transmission.