**Abstract**

The pericytes play a very important role in the central nervous system (CNS), concerning the formation of the functional neurovascular unit, serving as a substantial component in the development and maintenance of the stability of the blood-brain barrier (BBB). Besides, as pluripotent cells of neuroectodermal origin, the pericytes participate in autoimmune reactions and modulations, controlling the penetration of immune cells via BBB and playing an active role in lymphocytic trafficking and functional regulation, via cytokine secretion and activation. In demyelinating conditions, they participate in the restoration of the myelin sheath by modulating oligodendrocytes and stimulating the differentiation of oligodendrocyte progenitors. In the experimental model of allergic encephalomyelitis (EAE), electron microscopy reveals the proliferation and the morphological alterations of the pericytes as well as their interactions with endothelial cells and astrocytes, thus underlining the crucial role that pericytes play in the integrity of the BBB and the immune reactions of the CNS.

**Keywords:** pericytes, demyelinating conditions, electron microscope, BBB, EAE

## **1. Introduction**

Multiple sclerosis (MS) is among the most enigmatic disorders of the central nervous system, affecting a substantial number of patients, at any age from childhood to senility, inducing a large spectrum of physical and mental disability in a considerable number of them, with a high prevalence in Europe and North America [1].

The clinical diagnosis of multiple sclerosis is not always an easy task, due to the polymorphic and multidimensional pattern of the clinical manifestations of the disease, which might be associated with other disorders.

The phenomena and the severity of the disease would be evaluated based on the criteria of the expanded disability status scale (EDSS) [2].

The pathogenesis of MS, which has been considered as a chronic immunemediated disorder of the central nervous system (CNS) [3], has to be further clarified, although some risk factors such as genetic predisposition, viral, bacterial, or parasitic infections [4], climatic, environmental, and dietary factors [5], head trauma, and physical or psychological distress may play a substantial role in the puzzling etiological background of the disease.

Besides, the multidimensional underlying pathological mechanisms of multiple sclerosis, involving numerous cell interactions, molecular reactions, and activation of autoimmune responses via a multitude of signaling factors, result in inflammatory

#### *Demyelination Disorders*

infiltration, demyelination, gliosis, and axonal damage, which compose a very complicated labyrinthine pattern, causing a reasonable difficulty in the effectivity of any targeted therapeutical approach of the disease [6].

Among the many cellular components, which participate actively in the process of demyelination and remyelination, during the continuous neuropathological alterations and interactions in the brain and the spinal cord, during the long course of multiple sclerosis, the pericytes being heterogeneous cells [7] described by Rouget, originally called Rouget cells [8] and named pericytes by Zimmermann [9], seem to play a substantial role at any stage of the disease.

It is well known that brain pericytes are pluripotent progenitor cells of neuroectodermal origin [10, 11], which are located mostly around the blood vessels (peri, περι = around) and serve as substantial components of the bloodbrain barrier (BBB), being in direct contact with the endothelial cells, sharing a common basement membrane with them, and developing many functional interactions with endothelial cells, astrocytes, perivascular microglia, and macrophages [12].

It is important that the pericytes contribute to the formation of the functional neurovascular unit (NVU), which is composed of endothelial cells, pericytes, astrocytes, and neurons, and serve as a crucial structure for the integrity and functional stability of the central nervous system [13, 14]. The pericytes participate also in the development of the wall of small vessels, such as pre-capillary arterioles, capillaries, and post-capillary venules, enveloping the endothelium and being separated from them by a basement membrane (BM). Over most, the fact that the pericytes play a crucial role in the function of the blood-brain barrier [15] is of particular importance, particularly in the development of the tight junctions and in the vesicle trafficking in the endothelial cells, controlling the permeability of the BBB and participating effectively in its reconstruction and remodeling, in cases of anatomical disruption or functional decline, contributing therefore essentially in the stability of brain homeostasis [16].

A substantial body of evidence revealed that inducible pericyte knockdown in experimental animals resulted in disruption of the blood-brain barrier and rapid loss of neurons [17, 18].

It is important that the pericytes do frequently migrate in the neuropile space and even proliferate into different cellular types participating in a multitude of cell interactions [19].

Besides, pericytes participate in autoimmune reactions and modulations, mediating the neuroinflammation [19], and controlling the penetration of immune cells via BBB, playing an active role in lymphocytic trafficking and functional regulation via cytokine secretion and activation [20–22], and eventually contributing in glial scar formation [23].

The fact that pericytes are involved in the remyelination of the CNS, by modulating oligodendrocytes and stimulating the differentiation of oligodendrocyte progenitors [24], is of substantial validity.

The density of the pericytes varies from tissue to tissue, being the highest in the CNS, apart from the retina [25]. However, their number is not definitely stabilized, given that they could differentiate into other cell types, including glial cells and neurons under various conditions, in reaction to tissue injury [26].

For a further observation and detailed analysis of the gradual neuropathological phenomena and the cellular interactions, which occur in multiple sclerosis, animal models have been created by active immunization of susceptible recipients [27]. Among them, the experimental allergic encephalomyelitis (EAE) is the most frequently used animal model [27], which has been induced in genetically susceptible animals such as rats, mice, guinea pigs, rabbits, and monkeys by injecting

*Pericytes of the Brain in Demyelinating Conditions DOI: http://dx.doi.org/10.5772/intechopen.103167*

compounds that would stimulate the immune system, resulting in developing inflammatory perivascular infiltrates in the CNS [28].

In the majority of the experimental models, the injected immunogenic factor is derived from CNS proteins such as myelin basic protein (MBP), proteolipid protein (PLP), and myelin oligodendrocyte glycoprotein (MOG). The injected animals may develop neurological manifestations due to creation of inflammatory foci and demyelination in random areas of the CNS, in analogy to MS [29, 30].

Among the cellular components, the pericytes [31], the microglial cells, and the perivascular macrophages (PVM) [32] may play a substantial role in mediating neuroinflammation in the CNS in the EAE, as well as in MS and other autoimmune neurological conditions [32–34].

In the present study, we attempted to study the ultrastructural alterations of the pericytes around the capillaries and the venules of the brain in animals, which developed experimental allergic encephalomyelitis, knowing that there are some substantial limitations, due to the different pathogenetic mechanisms of the EAE, in correlation with MS [35].
