A blood-brain barrier is a rigid barrier which prevents damaging molecules in the blood from the brain. Beta-amyloid plaques, which are clusters of proteins found in the brains of Alzheimer’s patients, can damage neurons and compromise brain functions.
The detriments caused by beta-amyloid plaques in the brain can further damage the Alzheimer’s neurons by allowing the blood-clotting protein, thrombin, to enter the brain. Once the barrier is impaired, chemicals are secreted into the brain, which impedes brain functions and adversely affect neuron health.
Cells in the blood vessels that form a blood-brain barrier comprise specialized proteins that assist them in making tight junctions which act as tough seals in between cells.
Beta-amyloid plaques have a damaging effect on the brain known as the Cerebral Amyloid Angiopathy (CAA). Researchers believe that this effect allows detrimental substances to enter the brain more easily.
The researchers in the Massachusetts Institute of Technology (MIT) grew beta-amyloid plaques in a microfluidic channel, as well as the brain endothelium cells. The two projects were separated by an empty channel during the development of each tissue.
After ten days, collagen was introduced in the empty channel, which acted as a diffusion medium for the molecules to diffuse from one channel to the other. It was discovered that within three to six days, the beta-amyloid plaques had started adhering to the endothelium tissue, causing it to become leakier. The endothelium cells showed a reduction in the proteins that form tight barriers between cells and increased secretion of a particular enzyme that disrupted the layered matrix, which normally surrounds the blood vessels.
The breakdown of the blood-brain barrier resulted in an eased flow of thrombin from blood in the leaky blood vessels to the brain, where it can have adverse effects on neurons and harm neuron health.
Preventing the leakage
Next up, the researchers determined to test two types of antidotes that are FDA (Food and Drug Administration) approved to treat all kinds of conditions. These drugs were previously proven to strengthen the weak blood-brain barriers in relatively simple endothelium tissue models. The researchers discovered that the first drug, etodolac, worked very efficiently and effectively in solidifying the blood-brain barrier, while the other drug, beclomethasone, did little to stop and treat the leakages in the endothelium tissue experiments.
The backstory is that the leakages treated using etodolac caused the blood-brain barrier to become tighter and more rigid, and survival rates of neurons boosted. The MIT and Massachusetts General Hospital (MGH) have now teamed up with a drug discovery association to find other drugs that may be successful in revitalizing the blood-brain barrier in Alzheimer’s patients.
So far, treatments for Alzheimer’s have proven unsuccessful. Therefore, the researchers in MIT intend to use this method to identify more drugs that originate from single-cell screens, in order to pass them through a newly tested, complex process which could become a potential form of reliable treatment for Alzheimer’s patients.