Researchers at the Augusta University Medical College of Georgia have discovered an experimental compound reduces harmful inflammation following a stroke, improving patient outcomes.
The compound, known as compound 21, works by stimulating the angiotensin type 2 receptor, which is known to reduce inflammation and improve cell survival. It was tested in rat models which experienced a clot-based stroke—the most common type seen in humans. Though stroke size was not reduced, the rats had improved memory and movement in its aftermath.
“We don’t see acute neuroprotection, but it definitely affects long-term outcome,” Medical College of Georgia vascular physiologist Dr Adviye Ergul said.
“We think it will help the recovery and, at this moment, we really have no drugs to do that.”
In the preclinical studies, clots were created in the middle cerebral artery of otherwise healthy rats—a common site for large strokes in humans. Different doses of the compound were administered over five days, with the first dose given three, six, or 24 hours following the stroke. Some rats also received the clot buster tPA, the only US Food and Drug Administration (FDA) approved stroke medication, either two or four hours following the stroke, as well as compound 21 at three hours.
Though neither treatment course reduced the stroke size—with tPA proving itself essentially ineffective in the studies—rats that received even the lowest dose of compound 21 had less brain inflammation in the days following a stroke. These rats also had better results in cognitive tests, as well as better nerve and movement function.
“Our evidence to date indicated that compound 21 helps directly address lingering inflammation and its destructive impact,” University of Georgia College of Pharmacy assistant dean Dr Susan Fagan said.
Even high doses of compound 21 did not affect patient’s blood pressure, something which is important as there is conflicting evidence as to whether high or low pressure is bad following a stroke.
The researchers believe compound 21 has a two-fold benefit of inhibiting harmful effects of stroke such as inflammation and oxidative stress, as well as stimulating brain cell recovery through triggering brain-derived neurotrophic factor production, and blood vessel dilator nitric oxide production.
In a series of follow-up studies, the researchers are giving the compound as much as seven days following a stroke, as it moves from an acute to a more chronic stage. It is hoped that this will help the immune response be more reparative.
The researchers are also looking to answer questions such as whether the results are the same in female rats, as oestrogen provides a level of stroke protection that the male rats tested do not have. They will also examine the compound as a treatment for existing diseases such as hypertension and diabetes, which are two major stroke risks.
Previously, it was believed that declining cognitive capabilities occurred in patients who had experienced a number of strokes. However, evidence indicates that a destructive and lasting inflammation can follow an initial stroke, possibly damaging the brain for months following the stroke.
Currently, no treatment options which target this inflammation exist. Many stroke therapies which gave promising results in preclinical studies failed when transferred to humans. As a result, groups such as the National Institutes of Health have pushed for tighter regulations in study design and reproducibility of results in preclinical trials, ensuring lab studies mirror clinical scenarios as closely as possible.
In instances of stroke, these groups suggest studies should include blinding results, randomised enrolment of older animals and examining at the impact of tPA on the new therapy is being studies.
Strokes are the leading cause of disability in the US, and the fourth biggest cause of death in the UK.