Breakdown of the blood-brain barrier in stress alters cognitive dysfunction and induces brain pathology: New perspectives for neuroprotective strategies

Abstract

Emotional, psychological or environmental stress (e.g., heat or nanoparticles) influences brain function. However, the detailed mechanisms of stress induced brain dysfunction are not well known. Research carried out in our laboratory since last 20 years show that various kinds of stressors depending on their magnitude and durations alter the blood-brain barrier (BBB) permeability to proteins leading to brain pathology. These stressed animals also show marked behavioral and cognitive deficits at the time of the BBB leakage. Entry of several restricted elements from the blood to the brain compartment after breakdown of the BBB results in immunological, biochemical and pathological reaction causing brain edema formation and cell injury. Blockade of several neurochemical receptors, e.g., serotonin, prostaglandin or opioids as well as neutralization of key neurodestructive elements, i.e., neuronal nitric oxide synthase (nNOS), Tumor necrosis factor-alpha (TNF-α), dynorphin A or hemeoxygenase-2 (HO-2) using specific drugs or antibodies against these factors reduces BBB disturbances, cognitive and behavioral dysfunction, and brain pathology. Based on these new evidences, it appears that the BBB is the gateway to neuropsychiatric diseases. Thus, efforts should be made to maintain a healthy BBB in various brain diseases to achieve neuroprotection. The possible mechanisns of BBB breakdown and brain pathology in stress in relation to altered cognitive and sensory-motor functions is discussed in this review.