*5.1.1 Occludin and cerebrovascular injury-related diseases*

Brain has received extensive attention because it is the most vulnerable to endothelial barrier dysfunction. Under normal circumstances, the blood-brain barrier is a semipermeable interface, which is important for providing a neuronal microenvironment and exchanging water, ions, gases, and metabolites, but it is not suitable for exogenous harmful substances such as bacteria and viruses [4]. However, many triggers (e.g., inflammation, traumatic brain injury, ischemia) can lead to leakage of the blood-brain barrier, increasing the risk of cerebral edema, nerve damage, cerebral hemorrhage, and further increasing the risk of cerebral ischemia. The brain endothelial cell tight junction protein occludin plays an important role in maintaining the integrity of the blood-brain barrier. For example: (1) Both clinical and basic researchers have found

## *The Role of Occludin in Vascular Endothelial Protection DOI: http://dx.doi.org/10.5772/intechopen.107479*

that under cerebral ischemia, and cysteinase can hydrolyze the blood-brain barrier tight junction protein occludin to promote its release into the blood, resulting in an increase of occludin levels in serum. Therefore, serum occludin levels can be used as an indicator for predicting the severity of acute ischemic stroke, hemorrhagic transformation, and prognosis of patients [45]; (2) studies have shown that the increased permeability of the blood-brain barrier in type 1 diabetic mice may be due to the increased level of serum extracellular vesicle occludin, which affects the distribution of occludin in the cerebral vascular endothelial cell membrane [81]; (3) in rat model of traumatic shock, the expression of occludin in cerebral vascular endothelial cells is reduced, which affects the integrity of the blood-brain barrier, the leakage of inflammatory cells, and deterioration of vascular inflammatory response [82]; (4) both *in vitro* and *in vivo* studies found that the occludin degradation caused by autophagy is an important factor of the blood-brain barrier disorder when the brain is exposed to an ischemic environment [83]; (5) the increased expression of occludin in cerebral microvascular endothelial cells can reduce the apoptosis of endothelial cells by inhibiting the expression of apoptosis-related proteins, and the degradation of occludin makes cerebral blood vessels more prone to reperfusion injury [25, 84]; (6) in diabetic animal model, the expression of occludin in the cerebral vascular endothelium is reduced, which is manifested as diabetes complicated with cerebrovascular disease, and nerve damage, etc. [85]. In conclusion, abnormal expression, modification, and degradation of occludin may induce vascular endothelial dysfunction, resulting in injury of blood-brain barrier function, and ultimately aggravating the occurrence and development of brain diseases.
