**3. Crossing of the blood-brain barrier by** *T. gondii* **and molecular mechanism of damages**

Although the blood-brain barrier (BBB) is a solid barrier between blood and brain tissue, *T. gondii*'s superior tactics for crossing this barrier and reaching the brain have yet to be completely disclosed. However, it is still unclear whether neuroinvasion occurs via hiding within or as a direct tachyzoite outside the cell. The actual huge issue begins right here. Because TE, one of the most severe forms of the disease that may lead to death, develops when tachyzoites cross through the properly functioning BBB during acute infection [14]. The BBB is lined by microvascular endothelial cells, which are highly specialized. The key characteristics of this barrier are low pinocytic activity, restricted fenestration, and high trans-endothelial resistance. Thus, it functions as a structural and functional barrier with minimal permeability. Additionally, pericytes, microglia, and astrocytes are closely associated with BBB endothelial cells and substantially contribute to sustaining BBB activity [17–20]. It has been proven conclusively that the first transmission of *T. gondii* to the central nervous system (CNS) occurs primarily through the cortical capillaries [21]. It is crucial at this point to explore how this dissemination occurred. There is evidence that *T. gondii* manipulates gene expression in brain endothelial cells to cross the BBB via a "Trojan horse" strategy. *T. gondii* in cells expressing CD11b may play a significant role in the intracellular trafficking of the BBB [22]. In the same research, the percentage of CD45+/CD11bc+ cells infected with *T. gondii* tachyzoites was 13 times greater at the beginning of infection when compared with the population percentages. In this work, CD45+/CD11bc+ cells, both infected and uninfected, show the ability to breach the BBB in an in vitro culture model. Uninfected cells respond identically to infected cells, which is a surprise topic of debate at this level. Similar increases in the expression of intercellular adhesion molecule 1 and monocyte chemotactic protein-1 were reported after infection of brain endothelial cells with *T. gondii* tachyzoites within 2 and 12 hours, respectively [22]. CD11c- CD11b+ monocytes and CD11c+ CD11b+/− dendritic cells are the progenitor cells that facilitate the switch to the "Trojan horse" approach [23]. Although extracellular free-moving tachyzoites can cross the BBB without an intermediate, they can also do so *via* a variety of other mechanisms. Infection of the microvascular endothelium of the brain by tachyzoites, and their subsequent reproduction in the CNS is one potential approach [24]. Toxophyllin and protease expressions have been observed to assist the passage of *T. gondii* through the BBB. It has been shown that this transition is accomplished by destroying BBB cells [23, 25]. Because of this destruction, the BBB's permeability and integrity have been disrupted. Importantly, BBB disruption induces irreversible neurodegeneration and neuropathology in TE. In TE, *T. gondii* directly damages the blood-brain barrier (BBB) by inducing apoptosis in endothelial cells [26], while *T. gondii*-mediated oxidative stress (OS) [27] and nitrosative stress (NS) [28] also induce the same damage. Therefore, it is crucial to uncover the intricate processes involved in the pathophysiology of BBB degradation. It has been shown that von Willebrand Factor, closely related to a disintegrin and metalloprotease with thrombo-spondin 1 repeats family 13 (ADAMTS-13), plays an essential role in BBB permeability [29]. In addition, it has been underlined that ADAMTS-13 has neuroprotective roles by disclosing and decreasing BBB damage in the brains of small ruminants attacked with border disease virus [30] and listeric encephalitis [31]. Similarly, the expression of ADAMTS-13 has strongly shown BBB destruction in TE, and its neuroprotective activities have been described [26]. These results show that ADAMTS-13 has essential functions in the

*Neuroimmunopathology in Toxoplasmic Encephalitis DOI: http://dx.doi.org/10.5772/intechopen.109341*

BBB and neuronal parenchyma in disclosing the degree of BBB damage and reducing neuropathology. This essential initial step must be fully disclosed. Because a thorough understanding of the processes by which tachyzoites cross the BBB will aid in developing more focused therapies for preventing fatal brain injury. The primary aim should be to maintain the integrity of the BBB and prevent tachyzoites from entering the brain parenchyma during the acute infection phase. Thus, chronic TE may be avoided even before it begins.
