Astrocytic modulation of blood brain barrier: perspectives on Parkinson’s disease

Abstract

The blood–brain barrier (BBB) is a tightly regulated interface in the Central Nervous System (CNS) that regulates the exchange of molecules in and out from the brain thus maintaining the CNS homeostasis. It is mainly composed of endothelial cells (ECs), pericytes and astrocytes that create a neurovascular unit (NVU) with the adjacent neurons. Astrocytes are essential for the formation and maintenance of the BBB by providing secreted factors that lead to the adequate association between the cells of the BBB and the formation of strong tight junctions. Under neurological disorders, such as chronic cerebral ischemia, brain trauma, Epilepsy, Alzheimer and Parkinson’s Diseases, a disruption of the BBB takes place, involving a lost in the permeability of the barrier and phenotypical changes in both the ECs and astrocytes. In this aspect, it has been established that the process of reactive gliosis is a common feature of astrocytes during BBB disruption, which has a detrimental effect on the barrier function and a subsequent damage in neuronal survival. In this review we discuss the implications of astrocyte functions in the protection of the BBB, and in the development of Parkinson’s disease (PD) and related disorders. Additionally, we highlight the current and future strategies in astrocyte protection aimed at the development of restorative therapies for the BBB in pathological conditions.

Glial regulation of the blood-brain barrier in health and disease

“…Second, reactive astrocytes can also promote BBB function during a CNS insult [57,124]. Our group and others have shown that reactive perivascular astrocytes upregulate Shh in MS lesions [92,154].…”

“…The physical, molecular, and transporter barrier properties of the BBB are each responsible for maintaining CNS homeostasis [1,45,52]. Histopathological analysis of various neurologic diseases have revealed that BBB dysregulation and breakdown is a common feature in many of these disorders, lending proof to the hypothesis that a functional BBB is required for a healthy CNS [2,6,49,[53][54][55][56][57]. Moreover, there is evidence that this works in the opposite direction as well; that a healthy CNS microenvironment is essential for maintaining the functional barrier properties of the BBB via cross-talk between neural cells and ECs [2].…”

Astrocytes Mediate Protective Actions of Estrogenic Compounds after Traumatic Brain Injury

“…This antioxidant activity of astrocytes helps to protect the neuron against the oxidative stress preventing the damage of DNA, RNA, and proteins [45, 46]. In this regard, previous works indicated that astrocytes are pivotal mediators in TBI due to their ability to provide neurons (and other cells) metabolic support [47-49]. …”

“…Astrocytes are recognized for being multifunctional housekeeping cells involved in a permanent cross-talk with neurons and other neighbouring glial cells [52]. They regulate the concentration of potassium, sodium and glutamate at the synaptic cleft [47-49], provide lactate and glutamine to neurons and participate in neuron signalling modulation [53-57]. …”

Transitory Increase of Hematoencephalic Barrier Permeability by Intracarotid Introduction of Ozonized Saline Solution

“…Junctions are dynamic structures capable to alter the size of intercellular gaps during some minutes by remodeling the cytoskeleton, and the pericapillary reaction of the astrocytes adjoining the capillaries signifies the increase of capillary wall permeability [14,15]. Alterations of the neuron ultrastructure were of the adaptive character in response to the action of the oxidative factor, and were characterized by the increase of block-synthesizing organelle activity.…”