23 October 2019

Haptoglobin against stroke

Patients who survived a brain hemorrhage may suffer from a delayed terrible complication – damage to nerve cells by free hemoglobin from destroyed red blood cells in the spilled blood. Researchers from the University of Zurich have discovered the protective effect of the haptoglobin protein, which prevents this effect.

Bleeding into the narrow space between the inner and middle meninges is life-threatening. This type of cerebral hemorrhage is usually associated with the sudden rupture of aneurysms (bulges on the arteries) in the vessels of the brain. A third of patients (and quite young ones) die after such a hemorrhage as a result of increased intracranial pressure. Even if doctors manage to stop the bleeding and stabilize the condition of patients, in the first two weeks there is a risk of brain damage leading to serious disorders or even death.

Free hemoglobin in the cerebrospinal fluid damages neurons

Despite the efforts of researchers, it is still impossible to prevent these serious consequences of bleeding into the subarachnoid space. An interdisciplinary team of researchers has tested a promising strategy: the protective protein haptoglobin circulating in the blood binds hemoglobin in the cerebrospinal fluid before it leads to brain damage.

Haptoglobin.jpg

A section of the brain of a laboratory animal after a stroke (right) and a few days after the introduction of haptoglobin. The penetration of hemoglobin (red) from the brain fluid (black area in the middle) into the brain tissue (blue) is blocked, protecting neurons from damage. Source: UZH.

The researchers observed that a few days after the hemorrhage, the accumulated blood slowly resolves, and hemoglobin from the destroyed red blood cells enters the cerebrospinal fluid. Thus, the protein, which is usually responsible for the transport of oxygen, is a serious cause of delayed neurological disorders. Using samples from patients, as well as using experiments on sheep, scientists were able to show that free hemoglobin leads to vascular spasm and penetrates deeply into brain tissue, where it directly damages neurons.

Haptoglobin binds hemoglobin and makes it harmless

The substance that makes hemoglobin so dangerous is iron, which is located in the center of the protein and has a high tendency to chemical reactions. The human body in the process of evolution has formed its own protective protein – haptoglobin. In the blood, haptoglobin binds free hemoglobin, thereby preventing its toxic effects on blood vessels and kidneys. But the concentration of haptoglobin in the brain is very low and does not provide sufficient protection against brain hemorrhages.

By injecting purified haptoglobin directly into the sheep's cerebrospinal fluid through a catheter, the researchers were able to trigger this natural defense mechanism. Haptoglobin prevented vasospasm and prevented free hemoglobin from entering the brain tissue.

A new approach to treatment

For patients who have suffered bleeding in the subarachnoid space, the results obtained are of great importance: This is an opportunity to prevent the toxic effect of free hemoglobin after intracranial hemorrhage and significantly improve the neurological prognosis, as well as the quality of life of patients in the long term.

Article by M. Hugelshofer et al. Haptoglobin administration into the subarachnoid space prevents hemoglobin-induced cerebral vasospasm published in the Journal of Clinical Investigation.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of Zurich: Protein in Blood Protects against Neuronal Damage after Brain Hemorrhage


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