Combined neuroprotection therapy shows promise in experimental stroke model


A new study conducted by scientists at Louisiana State University (LSU) Health New Orleans Neuroscience Center of Excellence (New Orleans, USA) reports that the additive neuroprotection of a combination of two omega-3 fatty acid-derived signalling molecules is more effective in protecting brain cells and increasing recovery from stroke than a single drug.

These findings—which involved an experimental model—have been published online in Cellular and Molecular Neurobiology.

“We discovered a compelling, effective combinatorial therapy in experimental stroke,” said Nicolas Bazan (LSU Health New Orleans Neuroscience Center, New Orleans, USA), senior author of the study. “Despite increasing knowledge of the physiologic, mechanistic and imaging characterisations of stroke, no effective neuroprotective therapy has been found to date. Most current work uses different approaches with a ‘single’ bullet therapy. Since stroke is so complex and due to multiple damaging factors, we extensively explored a multidisciplinary approach—a combinatorial therapy—that yielded promising beneficial results.”

The research team examined the bioactivity of Neuroprotectin D1 (NPD1), discovered by the Bazan lab in 2003, combined with Resolvin D1 (RvD1) in experimental stroke. These two neuroprotective molecules occur naturally in the brain; are derived from docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA); and have been shown to limit excessive inflammatory responses, regulate metabolism and immune cell functions, decrease the production of pro-inflammatory factors, and promote tissue repair and stability.

Under Bazan’s guidance, LSU Health New Orleans graduate student and first author of the study, Madigan Reid, designed and performed gene expression studies that showed the combination treatment elicited the selective expression of genes contributing to cell survival.

The scientists found that the combination therapy boosted the uptake of an anti-inflammatory, stroke-associated gene 123-fold; a gene that regulates new brain cell and blood vessel growth 100-fold; and two markers of the stability of the brain cells that regulate brain development, maintenance of neuronal networks, and injury repair, ten- and five-fold, respectively.

“We show that NPD1 plus RvD1 remarkably improves neurological function and reduces lesion volume in acute ischaemic stroke—when administered promptly in moderate doses,” said Ludmila Belayev (LSU Health New Orleans Neuroscience Center, New Orleans, USA). “We also demonstrated a broad therapeutic window of neuroprotection with moderate doses of NPD1 plus RvD1, such that treatment initiated even six hours after stroke onset is highly effective. This combinatorial therapy may promise future therapeutic development against ischaemic stroke.”

“The biological activity of NPD1 plus RvD1 is due to specific activation and modulation of signalling pathways associated with the immune system, inflammation, cell survival, and cell-cell interactions,” added Bazan. “These findings provide a major conceptual advance of broad therapeutic relevance for cell survival, brain function and, particularly, stroke and neurodegenerative diseases.”


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