According to the Centers for Disease Control and Prevention, someone in the United States has a stroke every 40 seconds. Every four minutes, someone dies of stroke. Every year, more than 795,000 people in the United States have a stroke. About 87% of all strokes are ischemic strokes, in which blood flow to the brain is blocked. Stroke is a leading cause of serious long-term disability and reduces mobility in more than half of stroke survivors age 65 and over.
Now researchers at the LSU Health New Orleans Neuroscience Center of Excellence claim that a combination of an LSU Health-patented drug and selected DHA derivatives is effective in protecting brain cells and increasing recovery after stroke than a single drug.
Their findings are published in the journal Brain Circulation in a paper titled, “Blocking pro-inflammatory platelet-activating factor receptors and activating cell survival pathways: A novel therapeutic strategy in experimental ischemic stroke.”
“Acute ischemic stroke triggers complex neurovascular, neuroinflammatory, and
synaptic alterations,” noted the researchers. “This study explores whether blocking pro‑inflammatory platelet‑activating factor receptor (PAF‑R) plus selected docosanoids after middle cerebral artery occlusion (MCAo) would lead to neurological recovery. The following small molecules were investigated: (a) LAU‑0901, a PAF‑R antagonist that blocks pro‑inflammatory signaling; and (b) derivatives of docosahexaenoic acid (DHA), neuroprotectin D1 (NPD1), and aspirin‑triggered NPD1 (AT‑NPD1), which activates cell survival pathways and are exert potent anti‑inflammatory activity in the brain.”
By using an experimental model, Nicolas Bazan, MD, PhD, Boyd Professor, professor of neurology, and director of the Neuroscience Center of Excellence at LSU Health New Orleans School of Medicine, and Ludmila Belayev, MD, LSU Health New Orleans professor of neuroscience, neurology, and neurosurgery, discovered this novel therapeutic strategy for ischemic stroke.
Ischemic stroke is one of three types of stroke. It’s also referred to as brain ischemia and cerebral ischemia. This type of stroke is caused by a blockage in an artery that supplies blood to the brain. The blockage reduces the blood flow and oxygen to the brain, leading to damage or death of brain cells. If circulation isn’t restored quickly, brain damage can be permanent.
In previous studies, Bazan showed that in addition to its anti-inflammatory properties, DHA, an essential omega-3 fatty acid, stimulates the production of Neuroprotectin D1 (NPD1), which protects brain cells.
Due to the lack of effective treatments in treating the complexity of stroke, the team decided to approach things in two angles: By blocking pro-inflammatory platelet-activating factor receptors (PAF-R) and activating cell-survival pathways. They found that treatment with LAU-0901, a synthetic molecule discovered in the Bazan lab that blocks pro-inflammatory platelet-activating factor, plus aspirin-triggered NPD1 (AT-NPD1) reduced the size of the damaged area in the brain and improved behavioral recovery.
“We discovered that these novel molecules promote neuronal cell survival with important anti-inflammatory activity,” explained Belayev. “This combinatorial therapy may hold promise for future therapeutic development against ischemic stroke.”
“Altogether our findings support our prediction that therapeutic efficacy would be enhanced using a combination of a PAF inhibitor, LAU‑0901, with selected docosanoids, as well as providing synergistic neuroprotection in the postischemic brain. This compound therapy restored pro‑homeostatic lipid mediators with improved neurological recovery and may hold promise for future therapeutic development against ischemic stroke,” concluded the researchers.
