Neuronal cytotoxic edema is implicated in neuronal injury and death, yet mitigating brain edema with osmotic and surgical interventions yields poor clinical outcomes. Importantly, neuronal swelling and its downstream consequences during early brain development remain poorly investigated, and new treatment approaches are needed. We explored Ca²⁺-dependent downstream effects after neuronal cytotoxic edema caused by diverse injuries in mice of both sexes using multiphoton Ca²⁺ imaging in vivo [Postnatal Day (P)12–17] and in acute brain slices (P8–12). After different excitotoxic insults, cytosolic GCaMP6s translocated into the nucleus after a few minutes in a subpopulation of neurons, persisting for hours. We used an automated morphology-detection algorithm to detect neuronal soma and quantified the nuclear translocation of GCaMP6s as the nuclear to cytosolic intensity (N/C ratio). Elevated neuronal N/C ratios occurred concurrently with persistent elevation in Ca²⁺ loads and could also occur independently from neuronal swelling. Electron microscopy revealed that the nuclear translocation was associated with the increased nuclear pore size. The nuclear accumulation of GCaMP6s in neurons led to neocortical circuit dysfunction, mitochondrial pathology, and increased cell death. Inhibiting calpains, a family of Ca²⁺-activated proteases, prevented elevated N/C ratios and neuronal swelling. In summary, in the developing brain, we identified a calpain-dependent alteration of nuclear transport in a subpopulation of neurons after disease-relevant insults leading to long-term circuit dysfunction and cell death. The nuclear translocation of GCaMP6 and other cytosolic proteins after acute excitotoxicity can be an early biomarker of brain injury in the developing brain.

We recently demonstrated that transient attenuation of Toll-like receptor 4 (TLR4) in dorsal root ganglion (DRG) neurons, can both prevent and reverse pain associated with chemotherapy-induced peripheral neuropathy (CIPN), a severe side effect of cancer chemotherapy, for which treatment options are limited. Given the reduced efficacy of opioid analgesics to treat neuropathic, compared with inflammatory pain, the cross talk between nociceptor TLR4 and mu-opioid receptors (MORs), and that MOR and TLR4 agonists induce hyperalgesic priming (priming), which also occurs in CIPN, we determined, using male rats, whether (1) antisense knockdown of nociceptor MOR attenuates CIPN, (2) and attenuates the priming associated with CIPN, and (3) CIPN also produces opioid-induced hyperalgesia (OIH). We found that intrathecal MOR antisense prevents and reverses hyperalgesia induced by oxaliplatin and paclitaxel, two common clinical chemotherapy agents. Oxaliplatin-induced priming was also markedly attenuated by MOR antisense. Additionally, intradermal morphine, at a dose that does not affect nociceptive threshold in controls, exacerbates mechanical hyperalgesia (OIH) in rats with CIPN, suggesting the presence of OIH. This OIH associated with CIPN is inhibited by interventions that reverse Type II priming [the combination of an inhibitor of Src and mitogen-activated protein kinase (MAPK)], an MOR antagonist, as well as a TLR4 antagonist. Our findings support a role of nociceptor MOR in oxaliplatin-induced pain and priming. We propose that priming and OIH are central to the symptom burden in CIPN, contributing to its chronicity and the limited efficacy of opioid analgesics to treat neuropathic pain.

A new book from the Smithsonian’s National Museum of African American History and Culture shows the images and impacts of athletes on and off the playing field

Bogotá- Latin America and the Caribbean is at a decisive juncture in its history. Thanks to its advancements in social, economic, and production-based terms, the region is on its way to [...]

More on Kathleen Turner and her show at Arena Stage: http://j.mp/T0IkkZ Before taking the stage in "Red Hot Patriot: The Kick-Ass Wit of Molly Ivins," Academy Award nominee Kathleen Turner discusses the woman who inspired the show.

The Black Death of 1348 was a devastating event, wiping out half the population of Britain. And in churches like this one, drawings on the wall provide a haunting visual record of the scale of the tragedy.

In 1619, George Yeardley, the newly appointed governor of Jamestown, made history: He convened 22 elected members of a burgeoning commonwealth, creating the first democratic assembly in America.

Historically feared by humans, brown bears were once aggressively hunted in the contiguous U.S. Because of this, 95% of these majestic creatures live in Alaska.

Uncover the dark and curious truth behind the death of one of America's most beloved authors, Edgar Allan Poe. For centuries, the circumstances surrounding his death have remained shrouded in mystery, sparking endless speculation and debate. Was it murder, disease, or something even more sinister? ___ A little more information: In 1849, Edgar Allan Poe was found delirious on the streets of Baltimore. He was taken to a hospital but died four days later, with no clear explanation for his condition. Theories about his demise range from alcoholism to rabies to a neurological disorder. Some suggest a more sinister plot, involving foul play or a conspiracy. Despite extensive speculation, Poe's death ultimately remains an enigma, adding to the haunting allure of his literary legacy. #unsolvedmysteries #gothicliterature #theraven #edgarallanpoe #truecrime #Smithsonianmagazine Subscribe: https://www.youtube.com/@SmithsonianMagazine Read more about the mystery of Edgar Allan Poe’s death here: https://www.smithsonianmag.com/history/still-mysterious-death-edgar-allan-poe-180952936/ How did Edgar Allan Poe become such a prolific and popular storyteller, even after his death? Learn more about his history here: https://www.smithsonianmag.com/arts-culture/edgar-allan-poe-became-era-premier-storyteller-180971001/ For more videos from Smithsonian Magazine: https://www.smithsonianmag.com/videos/ Get More Smithsonian Magazine: Official Site: https://www.smithsonianmag.com/ Facebook: https://www.facebook.com/smithsonianmagazine/ X: https://x.com/smithsonianmag Instagram: https://www.instagram.com/SmithsonianMagazine/ Digital Editorial Director: Brian Wolly Director of Programming: Nicki Marko Manager of Programming: Michelle Mehrtens Scriptwriter: Dan Wolf Video Editor and Narrator: Adam Benavides

Artist Abbot Thayer illustrated the prevalence of camouflage in the animal world and advocated using it as a military tactic

The grand buildings of Washington, D.C. would look quite different were it not for the work of Palladio. Read more at Smithsonian.com

Gasp! The answer will amaze you. Still Image Credit: MaFelipe / iStock

In WW2, the British made destroying German dams a key strategic target in order to kneecap the German industrial effort. To accomplish this, they needed a special plane to deliver the payload: the Lancaster Bomber.

Mathew Brady is known for his Civil War photography and groundbreaking work in the field. Read more about the Civil War at http://www.smithsonianmag.com/history-archaeology/Civil-War-History.html.

Atlantic staff writer Frank Foer interviews Damion Thomas about athletes moving from a position of apathy to engagement

This traveling exhibit reveals the mystery behind some of the women that helped shape this country's social and cultural landscape

Photographer Drew Gardner has a passion for history. His long-term project, “The Descendants,” (https://www.drewgardner.com/descendants)  wherein he recreates famous portraits of historical figures featuring their direct offspring, is his most visible expression of this interest. But like a lot of people who study history, Gardner has in recent years begun to contemplate more deeply the question of whose stories have been judged worthy of preservation, and whose have been allowed to fade into obscurity. That was how he decided to shift his specific focus to locating and photographing Black American descendants of Civil War veterans. You can take a look at Gardner’s photographs and read magazine editor Jennie Rothenberg Gritz’s exploration of their meaning here (https://www.smithsonianmag.com/history/descendants-black-civil-war-heroes-wear-heritage-pride-180983397/) . On the latest episode of the Smithsonian podcast “There’s More to That,” (https://www.smithsonianmag.com/podcast)  I speak with Janisse Flowers and her 9-year-son, Neikoye, who are descended from the Civil War drummer boy David Miles Moore Jr. After some reflection, Janisse and her husband decided to grant Gardner’s request to photograph Neikoye dressed in a replica of Moore’s Union Army uniform. Both Janisse and Neikoye share their surprise over how this experience made them more conscious of their heritage. I’m also joined by Gardner himself, who describes the challenges—and, he hopes, the potential benefits—of asking Black Americans to revisit one of the most painful chapters of America’s history by (almost) literally stepping into their ancestors’ shoes. You can learn more about Drew and his work at his website (https://www.drewgardner.com/) . Find prior episodes of our show here (https://www.smithsonianmag.com/podcast/) . There’s More to That is a production of Smithsonian magazine and PRX Productions. From the magazine, our team is Chris Klimek, Debra Rosenberg and Brian Wolly. From PRX, our team is Jessica Miller, Adriana Rosas Rivera, Genevieve Sponsler, Terence Bernardo, and Edwin Ochoa. The Executive Producer of PRX Productions is Jocelyn Gonzales. Fact-checking by Stephanie Abramson. Episode artwork by Emily Lankiewicz. Music by APM Music.

Regular dust bathing removes pest and parasites and keeps the wild bird's iridescent feathers in top condition. (Credit: Carla Rhodes)

A new paper analyzes three decades of fatalities around the world and predicts how "superbugs" will affect human health in the future

The annual award ceremony featured costumes, songs and paper airplanes as scientists recognized comedic research across ten disciplines

Kleptoparasitism, in which a bird harasses another to steal its food, might introduce avian flu to the continent, currently the only one without the severe H5N1 strain

The artist's cityscapes, once dismissed as too masculine, would later influence the floral artworks that became central to her iconic style

The discoveries include sharks, shorebirds, mammals and saber-toothed salmon, with the oldest remains dating to almost nine million years ago

New research suggests the sarcophagus' occupant, previously known only as "the horseman," is Joachim du Bellay, a French Renaissance poet who died in 1560

A blockbuster exhibition in London examines the Dutch Post-Impressionist's creative output between 1888 and 1890, which was one of the most productive periods of his career

Experts are carefully uncovering traces of the original paint and fragments of gold leaf that once adorned the 2,000-year-old Temple of Edfu

Researchers say that the iconic painting's swirling sky lines up with Kolmogorov's theory of turbulence, suggesting that the artist was a careful observer of the world around him

The so-called good-luck flag, which hung on an American veteran's wall for many years, returned home last month after nearly eight decades

If the structures look familiar, it's probably because nature has been using them for a long time in places like nautilus shells, zebra stripes and onions

The recent excavation beneath the Treasury has revealed 12 complete human skeletons and a trove of grave goods dating back 2,000 years

At a new park in Bosnia and Herzegovina, two dozen gardeners have spent years replicating the Dutch artist's masterpiece using the land as their canvas

Each of the 11 dolphins sampled exhaled at least one suspected particle of microplastic, which researchers say “highlights how extensive environmental microplastic pollution is”

The discovery of worms and snails confirms that these still-mysterious, dark hotspots of life extend beyond what’s visible above the crust

Called M136279841, the value belongs to a rare class of prime numbers called Mersenne primes and was found using a supercomputer system spread across 17 countries

Chinook salmon spark excitement among local Klamath Tribes, who have advocated for decades to restore the flow of the river in California and Oregon

Study participants with lifelong anosmia sniffed less than those with a normal sense of smell. Future research could shed light on whether this has negative implications for their health

Despite its unusually small size, the newly unearthed House of Phaedra is covered in elaborate frescos depicting mythological scenes

Grizzly 399 became a celebrity of Grand Teton National Park in her lifetime. Now, her death has drawn attention to wildlife-vehicle collisions and how they might be reduced

By analyzing an old lidar survey, researchers found evidence of more than 6,500 ancient structures in a previously unexplored area of Campeche

Ne’Kiya Jackson and Calcea Johnson of Louisiana published a new study proving the Pythagorean theorem using trigonometry, a feat mathematicians long thought could not be done

This brief chapter of art history is often overlooked. Now, an exhibition in New York City makes a strong argument for the integral role played by four artists in the city of Siena

The beloved reptile in Australia died last weekend and was thought to be up to 120 years old, though that age is only an estimate. Research on his bones might reveal a more exact number

The viral king penguin chick at Sea Life Melbourne Aquarium is beginning to lose his youthful down, a process that will give him his distinctive and waterproof adult plumage

This story and others have come to light during a project to translate and digitize a series of texts about archbishops in York, England

Sławomir and Szymon Milewski were searching for a Roman road when they stumbled upon the cache of coins, which is worth more than $120,000

In the international competition, people with physical disabilities put state-of-the-art devices to the test as they race to complete the tasks of everyday life

Adverse weather has cancelled ferry crossings between Newfoundland and Labrador and Nova Scotia heading into the long weekend.

As Week 3 of the provincial election campaign begins, there are questions about how Nova Scotia's major political parties plan to combat the rising number of opioid overdose deaths. 

Loved ones, friends, and people from across the city have all come together to support each other at Pastel Rita, the café Jocelyn Després helped so many call home.

New Brunswick’s Court of Appeal has reserved judgment in the case of a man found guilty of criminal negligence in the death of Fredericton teenager in 2018.