Science Concentrates NEUROSCIENCE
Boosting recovery after brain damage
In the minutes after a stroke, the sudden loss of blood supply to a region of a person’s brain can start damaging brain cells. Acute therapies to restore blood flow can protect neurons near the damaged cells, if the person receives treatment in the hours after the stroke. But once that window closes, doctors have few therapeutic options. Damaged neurons can impair stroke patients’ cognitive abilities and motor skills. However, with rehabilitation, affected people can recover some lost function thanks to the brain’s ability to rewire its circuitry—known as synaptic plasticity. OH OH Now, sciN O O entists at Yokohama City O University and Fujifilm’s ToyaEdonerpic maleate OH ma Chemical report that the small molecule edonerpic maleate, when administered in combination with physical training, accelerates the recovery of lost motor function caused by a brain injury in mice and monkeys (Science 2018, DOI: 10.1126/science.aao2300). Toyama had previously sponsored Phase I/II clinical trials of edonerpic maleate for treating Alzheimer’s disease. The trials demonstrated that the molecule was safe but not efficacious. But because the compound protected neurons in preclinical studies, the research team behind the new work decided to test the molecule’s ability to recover function after stroke-like brain injuries. The team tested the compound in two-month-old male mice and five-year-old macaque monkeys that had received brain injuries. The scientists tested the animals’ motor skills before and after the injury. Those receiving rehabiliative training and oral doses of edonerpic maleate starting one day after injury recovered more motor function after the injury than those that didn’t receive both. Louise D. McCullough, who studies stroke at the University of Texas Health Science Center, says the findings are provocative but need to be validated. Translating the results to people may be somewhat limited because the team tested only young, male animals. Many researchers have reported sex and age differences in the response to brain injuries, she says. The authors plan to evaluate edonerpic maleate in a 40-person Phase II clinical trial slated to start by early 2019.—TIEN NGUYEN
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C&EN | CEN.ACS.ORG | APRIL 9, 2018
The Pinnacles at Gunung Mulu National Park in Borneo are made from limestone that can weather and release nitrogen into the soil.
ENVIRONMENT
Rocks are a sizable source of nitrogen This missing piece of the nitrogen cycle may have climate implications Nitrogen gets around on Earth. The element moves between the atmosphere, oceans, land, crust, and mantle of the planet. But models of this nitrogen cycle are in need of a major update, a group of biogeochemists says. The researchers claim the models omit about 15 teragrams of nitrogen produced by rock weathering (Science 2018, DOI: 10.1126/science.aan4399). The implications of this omission are unclear, but some researchers say correcting it may fine-tune climate models. Scientists have always assumed nitrogen enters land-based ecosystems from the air, not from geological sources. But geologists have long known that rocks, especially sedimentary rocks, contain varying concentrations of nitrogen, much of it in forms that organisms can use. Through tectonic upheaval, physical and chemical weathering, and other processes, these nitrogenous compounds can move into the soil, just as other nutrients do. In a new paper, Benjamin Houlton, a biogeochemist at the University of California, Davis. and colleagues used models of physical and chemical weathering to predict that rocks release 11 to 18 Tg of the nutrient into the soil per year. As a comparison, before the industrial era, the land and atmosphere exchanged about 100 Tg of nitrogen per year. Houlton expects that adding rocks into the nitrogen cycle may affect climate change forecasts to some extent. Plants currently absorb about 30% of human carbon dioxide emissions, Houlton says. Their ability to do this is limited by how much nitrogen they have access to because they need the nutrient to make biomolecules. “If there is more nitrogen there than expected, then the constraints on plant growth in a high-CO2 world may not be as great as we think,” says Ronald Amundson, who studies soil biogeochemistry at the University of California, Berkeley. William Schlesinger, a biogeochemist and president emeritus of the Cary Institute of Ecosystem Studies, is more skeptical. Rock nitrogen is probably insignificant on a planetary scale, though it may be important locally in some places, he says. Schlesinger expects the effects of rock nitrogen on the carbon cycle would be small enough to fall into the margin of error of climate models.—KATHERINE BOURZAC, special to C&EN
C R E D I T: PAU L WH I T E
Compound helps mice and macaques regain motor skills after stroke-like brain injuries
