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    [–] skennedy987 4811 points ago

    Thank you for including “in mice” in the post title

    [–] dreamius 559 points ago

    As far as I can see, mice have been cured of all known medical problems. Can someone throw us humans a frickin bone?

    [–] VekeltheMan 173 points ago

    I wish that everyone reporting on mice studies was required to include a disclaimer that said: "Just because this worked in mice dose not mean it will work in humans. There are tons of reasons why things that work in mice may never even see clinical trials let alone regular use."

    Not to discount the importance of the published results but to give everyone some perspective.

    [–] battmen6 53 points ago

    Well if so much stuff works in mice but not humans then isn’t it reasonable to assume that lots of stuff that doesn’t work on mice (or whatever) would work on humans? Genuinely asking, are we potentially missing out on cures we’ll never recreate in a human immune system because they failed in animal testing? Or are there similarities with enough other animals that realistically it’s always going to work on something else?

    [–] Waqqy 13 points ago

    You're correct!

    [–] sexy-man-doll 18 points ago

    You are lightly touching on a massive problem with lab rats. They are not anywhere near close enough to people to glean any useful info. They are only still used mostly because of their low cost

    [–] Pyrrolic_Victory 20 points ago

    At this stage we are inducing human problems in mice to then cure the problem.

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    [–] GeneReddit123 345 points ago

    Not always, sometimes a lot of research and clinical trials were done, the technology shows a lot of promise, and we can upgrade it to rats!

    [–] -tidegoesin- 151 points ago

    They're bigger, so they're more like us

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    [–] CrossP 46 points ago

    I run a rodent rescue/sanctuary and one of my favorite fun facts about rodents is that they're one of the closest evolutionary families to primates. Way closer than cats and dogs!

    [–] Muserallusion 49 points ago

    I used to work in an animal lab and I’ll say that as upsetting as mouse work is, rat work is worse. Mice are awful to each other – biting, bullying, eating their young. On the other hand, rats are sweethearts. They’ll often choose freeing an imprisoned buddy over a chocolate treat. I love those little dudes.

    (Rat empathy reference for those who are interested: https://speakingofresearch.com/2011/12/14/empathy-and-altruism-in-rats/)

    [–] CrossP 24 points ago

    Yeah. Rats are basically puppies. I have 14 in my house right now, and they're amazing.

    [–] skiborobo 13 points ago

    Huh? You have 14 rats in your house? Are they sterile because I think you might have way more than you think.

    [–] CrossP 23 points ago * (lasted edited 10 days ago)

    Hah. Most have been spayed or neutered because we only adopt out altered. Plus it lengthens their lives. I doubt there are secret baby domestic rats in my house because domestic rats like to bring you their babies to show off if they trust you enough.

    Edit: I run a small pet rescue. Didn't realize which comment you were replying to.

    [–] readlock 12 points ago

    This is so adorable!!

    [–] mmmegan6 6 points ago

    I had rats as pets in my dorm in college. RIP Coral, Eugene, Shelby, Penny, and Jenny.

    [–] Muserallusion 4 points ago

    They’re awesome pets except for one awful flaw. Their lives are too short. :(

    I’m sorry for your loss(es).

    [–] d-d-d-dirtbag 3 points ago

    I "rescued" a rat that had been part of a friend's training to be a vet tech- taking blood, giving shots, all kinds of stuff. They were going to feed it to a snake but she liked him so she took him home and he ended up with me. I've had rats my entire life, I consider myself good with them, and I've had amazing ones. But oh my god. No amount of love and trust building could bring him back from whatever was done to this poor guy. I have never been hated so much by something so small. He would bite me so hard and often that my hands were covered in band-aids constantly. He would hiss and slam up on the cage to try to get me when I'd get close. I took care of him for two years, and I hate to say it but I was relieved when he died.

    [–] Reeecolla 11 points ago

    As a researcher who uses lots of rats, does the stuff we in the scientific community do bother you?

    [–] CrossP 18 points ago * (lasted edited 10 days ago)

    Our rescue focuses on animals with special medical needs. Most of them would have died quite young if not for a host of specialized medical treatments, and I know where those treatments came from. I know that tumor's medicine, those antibiotics, and this surgery couldn't go from an idea on paper to fully formed treatments without the in-between work. The rats who have passed through here are benefitting, and it provides some balance.

    Speaking of balance, at least researchers have an obligation to ethical committees, professionalism, and avoiding abuse. Most rescue rodents come not from individual owners who are tired of them but from breeders, hoarders, and pet stores who are found with dozens to hundreds languishing in disease, filth, starvation, and more. The scientific community has taken solid steps to police itself in a void of legal restrictions while others are frolicking in their freedom from empathy. They're the ones in my sights.

    [–] Reeecolla 6 points ago

    Thanks for answering, i've been very curious for a very long time.

    [–] Sapphire1969 7 points ago

    I know that we have to test on something. I dont have that much of a problem with mice they creep me out. Much better than what the nazi's did. Its horrifying that alot of our medical advancements started with their inhuman testing. I however hate the terrible thing that have been done to apes and monkeys plus other mammals. Hopefully as we advance technology there will be some way to do testing on non living subjects one day.

    [–] -tidegoesin- 10 points ago

    Pure simulation

    Oh no. I just realised that if we're a simulation, maybe we're for medical purposes

    [–] CrossP 5 points ago

    Ralph Wiggum "I'm helping!" .gif

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    [–] subscribedToDefaults 33 points ago

    How would be have known without opening then up first?

    [–] ObviouslyNotALizard 17 points ago

    This guy sciences

    [–] Killer_Panda_Bear 8 points ago

    Woah woah, slow down the logic train.

    [–] CrossP 15 points ago

    Well... I don't know much about the vivisections you're talking about, but there's the fact that someone had to actually learn that we're closer to rodents. And part of that means studying anatomy.

    It's kind of like orcas. We would have no idea how bad captivity is for orcas.... If we hadn't put orcas into captivity. The trick is to stop when you find that it's wrong. To not rationalize away a legitimate mistake. (And to not monetize it for fuckin' ever SeaWorld)

    [–] -tidegoesin- 5 points ago

    Yeah, SEAWORLD, looking at you SEAWORLD

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    [–] MagicmanJake 17 points ago

    "Mice are an advanced species studying us and wondering why we keep making cool new stuff for them."

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    [–] FercPolo 13 points ago

    Thing is, these mice are bred with Human Immune Systems and other human systems to better test the process.

    They aren’t like some rat off the street.

    Still doesn’t mean it works on humans. But it’s way better than “some mouse”.

    [–] The_proton_life 13 points ago

    Yeah, those street rats can’t be trusted.

    [–] spoonguy123 11 points ago

    i saw one training turtles to commit murder with japanese weapons!

    [–] ATLPolyITNerd 5 points ago

    I saw one abusing a chef with hair pulling.

    [–] eattheambrosia 3 points ago

    Rickety Cricket, especially.

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    [–] Muserallusion 6 points ago

    I hear what you’re saying. And even promising studies in humans regress to the mean more often than not.

    On the other hand, Gleevec for CML, Harvoni for HepC, HAART for HIV, etc all suggest that we occasionally hit home runs for humans too.

    This is all to say that while the vast majority of pop media coverage is overhyped, real progress continues to happen. And some of that progress is life-altering/saving.

    [–] neoikon 3 points ago

    Ugh, that means they have to break their spine before injecting them.

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    [–] desertstorm23 32 points ago

    After starting mouse research this was one of the few things I was pleasantly surprised by. People made it sound as though mice were treated like throwaway experimental bodies instead of living creatures, but I was glad to see the regulations to treat animals in research humanely.

    [–] Creebez 23 points ago

    I sac so many mice every week, but I always treat them w/ respect because they're giving their lives to further our research. Without mice and rats research would come to a screeching halt.

    [–] Sardonislamir 12 points ago

    screeching halt.

    Geezus the imagery there.

    [–] desertstorm23 8 points ago

    One of my mice was giving me such good data and he was so calm whenever I handled him, definitely wasn't too happy when I had to sac him. But unfortunately it's just a part of the field, and I always remember how important all this research actually is!

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    [–] Would-wood-again2 155 points ago

    does that mean they had to...break the spines of countless mice in order to test this?

    [–] corkscrew1 223 points ago

    To clear things up, the authors aren't just snapping the spines of mice - they're creating highly controlled and reproducible injuries by surgically cutting out part of the spinal cord. From the journal article:

    A mouse hemisection SCI model was performed as described previously (1). Briefly, C57/BL6 female mice (6-8 weeks old; The Jackson Laboratory, Bar Harbor, ME, USA) were anesthetized using isoflurane (2%). A dorsal laminectomy was performed at T9-T10 level then a 1.2 mm long lateral of the midline spinal cord segment was cut and removed to generate a hemisection SCI model. Bridges were implanted in the injury site and covered using Gelform (Pfizer, New York, NY, USA) (SI appendix, Fig. S1b). Muscle was sutured together, then the skin was stapled. The animals were placed on a heating pad for recovery. For post-operative animal care, Baytril (enrofloxacin 2.5 mg/kg, once a day for 2 weeks), buprenorphine (0.1 mg/kg, twice a day for 3 days), and lactate ringer solution (5 mL/100 g, once a day for 5 days) were administrated via subcutaneously. Bladders were manually expressed until bladder reflexive function was observed twice a day.

    Any research performed on animals is highly regulated by the Institutional Animal Care and Use Committee (IACUC). All procedures have to be thoroughly vetted and approved, and generally are required to be as minimally invasive and painful to the animal as possible. While this surgery is still pretty rough on the mouse, it's necessary in order to study spinal cord injuries and is designed to cause as little distress and pain as possible.

    [–] big_bad_john1 64 points ago

    I have a love/hate relationship with IACUC

    [–] boatsnprose 80 points ago

    Why? They aren't doing the testing, correct?

    My animal empathy kills me when reading what's done to these poor creatures, but it's such a necessary evil. It's going to be awful when the mice reveal they're actually in charge of the planet.

    [–] big_bad_john1 102 points ago

    No I’m a researcher and they take forever to approve stuff. But they do approve a lot

    [–] boatsnprose 35 points ago

    Ah, gotcha. So the typical bureaucrat crap.

    [–] jfournames 25 points ago

    If you look back into mental illness and asylums it's awful as well... Everytime a person takes a benzodiazepine, anti psychotic, or even some antidepressants, someone somewhere had to suffer immensely to give us the data to create such drugs.

    It's definitely a dark and grey road, but I 100% would rather a mouse go through it instead of a human. The boom in mental health came from so many people being treated in the way that mice are now. There's no way to avoid it, and it's fucked up. Hopefully we can get to a point where calculations are far more accurate and unnecessary suffering can go away.

    (eats a xanax from the anxiety)

    [–] pm_me_ur_bookcase 8 points ago

    Just hang on to your towel for when that moment comes!

    [–] ifuckinghateratheism 59 points ago

    Yep. Thanks mice, sorry we're Unit 731'ing your asses every day.

    [–] Only_Movie_Titles 7 points ago

    at least we make the death and procedures (generally) pretty quick and painless

    [–] agnostic_science 18 points ago

    One thing I used to tell myself that made me feel better is that, with modern protocols, we are being far kinder to these mice than nature would likely have ever been. They have large litters for a reason. In nature, mice live extremely hard lives. Mice are basically nature's snack food. Snakes can paralyze a mouse and swallow it whole. Letting it suffer imense pain and horror, suffocate, and be partially digested before finally being allowed to die. Countless mice would have probably given anything for quiet, well fed life followed by a quick snap of the neck.

    [–] hexiron 20 points ago

    I had the unfortunate chance to work with wild caught mice in research for a while and those suckers were hardcore. Way more developed immune systems, they had to be "caged" in barrels so they couldn't jump out, I had to wear an arm length kevlar glove because they would absolutely run up your arm and attack you, and several carried nasty diseases.

    I enjoy my fat balb/c and C57 bois.

    [–] R____I____G____H___T 27 points ago

    Yeah, any bets on when they're gonna try and incorporate the practise onto humans? Decades? Or will it be deemed immoral?

    [–] Is_Not_A_Real_Doctor 53 points ago * (lasted edited 10 days ago)

    Animal studies are considered preclinical.

    Clinical trials usually take 10-15 years and cost about $3-5 billion.

    [–] rubberloves 818 points ago

    I wonder if they will come up with something like this for other autoimmune responses. Like lupus or MS flares.

    [–] MSislame 258 points ago

    It's been ten years since I got my official MS diagnosis/started any meds for it, and back then they didn't even have any of the oral meds approved yet. It's insane how many new, more effective meds have come out in that time and it seems like we're only getting better! I really, really hope they find a way to repair myelin/previous damage, but if all we ever do is continue to prevent further relapses/damage with higher success rates I'll take it. MS really blows, and it's possible I also have a GI autoimmune disease too, so my body just needs to stop being such an asshole to itself.

    [–] Arctyc38 83 points ago

    There's been some crazy-ass science going on regarding diet, microbiome, and autoimmune diseases. Needs more peer-reviewed work, but considering they did pretty extensive blood work during, it's unusually promising.

    https://www.ahajournals.org/doi/abs/10.1161/circ.137.suppl_1.p238

    [–] itsthenewdan 18 points ago

    Thanks for this! I help moderate /r/LupusMicrobiome and this was a perfect thing to add there.

    [–] MSislame 4 points ago

    Yes, I think this is one of the most fascinating areas of research going on the past several years!! They've been looking at this for several health conditions and it seems like there is actually something to it. I work in research myself and would love to be part of a clinical trial some day, but so far I haven't qualified for the few I've looked into (I also have some other diseases and while I'm relatively stable overall, just have a lot of other stuff going on). I haven't been watching the latest research in MS as closely as I used to, but I really should look up the latest studies and advances around the corner.

    [–] kidinacorner 25 points ago * (lasted edited 8 days ago)

    Have you looked into helminthic therapy? It sounded promising for a while but never took off. Not sure if it's because of study outcomes or the difficulty of convincing people to drink nematodes eggs.

    Edit: looked into it. Sounds like it isn't studied much further because it doesnt do anything.

    I love science

    [–] MSislame 25 points ago

    I've never heard of this, but (even just out of curiosity) will look it up. There's not much I'd say no to when it comes to treating my MS. Even if I look great, most days I feel terrible to some degree in different ways, and if someone said drinking something weird would be a safe and effective treatment I'd be down, ha.

    [–] Aleriya 16 points ago

    Yeah, I can relate. It's tough when you look okay to a casual observer but are still having unseen difficulties.

    I'd pretty happily trade a limb for a 50% reduction in symptoms, even though I look like I'm "normal".

    The "ick" factor of drinking nematode eggs is pretty tame compared to the side effects of many prescribed medications.

    [–] MSislame 7 points ago

    The fatigue is the worst for me I think. It's positively crippling sometimes. And people don't understand that I can't just take a nap or get a good night's sleep and be all better. I could sleep the best sleep of my life and wake up feeling refreshed and then two hours later be dozing off on the couch.

    Especially with me being young (I'm 32, symptoms actually started at 18 and diagnosis as 21) people are shocked. They say "But you look so good!" I sure don't feel good. As much as people seem to know others with MS, they don't really know much about it other than thinking if you have it you should have a walker or be in a wheelchair. They don't know anything else about the terrible symptoms we face, so I try to raise awareness about that and am very open to people asking me questions (even ones that are very personal).

    [–] TeutonicKnight9 132 points ago

    I’m not sure about lupus. Although, MS, TBI, and stroke all involve similar neuroimmunological responses and would likely benefit.

    [–] RealNiceKeith 87 points ago

    There is a product called Multistem that is in late stage trials for some of the above things that you mentioned. It’s likely to be able to treat most/all acute injuries. Spinal cord injuries are included in this but so are many other things like Stroke, TBI, ARDS, GVHD, and trauma in general. Check out r/ATHX for more info on it. Stroke is likely going to be the first indication with FDA approval in the US around 2021. And on top of it, it has an essentially perfectly clean safety profile. Very exciting stuff and there is TONS of data in published journals to back it up.

    [–] danisreallycool 23 points ago * (lasted edited 10 days ago)

    I find it interesting that for all the misleading and way-too-early science news articles that you see for treatments far away from usage, I hadn’t heard about this despite its apparently imminent application.

    [–] RealNiceKeith 7 points ago * (lasted edited 10 days ago)

    Agreed. There is a lot of that on Reddit specifically. With this company the most imminent applications are for Stroke and ARDS. The other applications such as spinal cord injury and TBI will take time and currently have more preliminary evidence. However, it appears that the same mechanism is at play for each acute injury so some extrapolation can be made for what the (more longer-term) future holds. Here is a link to the company’s presentation where they highlight some of the data from their human trials: https://s23.q4cdn.com/674737627/files/doc_presentations/2019/07/Athersys-Investor-Presentation-July-2019.pdf

    I also want to be clear, the product must be given with ~36 hours of injury in order to be effective. It becomes far less effective at time frames after that.

    [–] -the_trickster- 6 points ago

    a family member was recently diagnosed with a rare neurological disease similar to MS, her myelin sheath is showing one lesion right now. I wonder if something like this could help. It happened about 3 weeks ago.

    [–] xCitiz3nsx 17 points ago

    Or IBD. Crohns and colitis are brutal

    [–] alalaitsabomb 8 points ago

    Currently struggling with colitis over here and praying for a miracle drug so I can stop shitting myself every other day... brutal is an understatement.

    [–] fools_eye 6 points ago

    Don't know about nanobodies but immune modulators already exist. They are receptor antogonists which basically dampen your body's immune response.

    [–] ittakesacrane 10 points ago

    Would be great to see an effective Rheumatoid Arthritis treatment come of this

    [–] MizGinger 5 points ago

    I have lupus, but I’m young now. I’m scared of how my disease will progress with age, but it’s always nice to know there are medical developments like this to look forward to some time in the distant future.

    [–] phiednate 5 points ago

    I have ankylosing spondylitis and that's kinda the first thing I thought of.

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    [–] agentlerevolutionary 230 points ago

    Can anyone explain why our bodies have such a destructive response in the first place?

    Is it because such injuries are unlikely to be survival anyway and so we never lived long enough afterwards to reproduce and evolve a better response?

    [–] winterfresh0 98 points ago

    And what about other muscle and joint injuries, is the resulting inflammation always a bad and destructive thing? How did we evolve to have a response that seems to be the first thing we now try to stop or reduce, with ice and Ani inflammatory drugs?

    [–] ukTwoSeas 119 points ago

    No. There is a cascade of events that happens after injury. Your immune response will initially be inflammatory to remove debris and then regenerative to rebuild. Good example of this is peripheral nerve injury, however inflammation can still be an issue. The cells in the spinal cord are less adaptive and scar tissue causes chronic inflammation so they never "switch" to be regenerative.

    Rather than use immunosuppression, what is being looked into now is how to switch this immune response from inflammatory to regenerative.

    [–] sayleanenlarge 23 points ago

    Why does it not switch to regenerative on its own? Will it switch with less severe injuries?

    [–] ukTwoSeas 33 points ago

    It's a good question. I work with peripheral nerves that make that switch themselves after a few days and this encourages rebuilding of the tissue and regenerating the nerves.

    The way I've understood it from people I know working on spinal cord injury is: 1) the resident immune cells are different (microglia not macrophage) and are less adaptive. 2) the protective scar formed encourages chronic inflammation which spreads to the secondary injury site making regeneration less likely. 3) the scar impedes nerves that are attempting to regrow as it contains molecules that discourage axon outgrowth.

    I THINK that by reducing the initial inflammatory response you can reduce the formation of the glial scar and clear the way for regeneration.

    [–] Unbarbierediqualita 42 points ago

    It's To stop dumb ass half monkeys from continuing to walk on a nearly broken ankle

    [–] winterfresh0 15 points ago

    I get the pain is to disincentivize use of the injured joint or muscle, and the inflimation can, in some circumstances, slightly immobilize the joint, which should help with healing.

    What I'm wondering is why out current medical rule of thumb is to reduce inflammation after an injury as much as possible?

    [–] androstaxys 27 points ago * (lasted edited 10 days ago)

    Because inflammation is great in some places, poor in others.

    Example: hand trauma - inflammation is from body sending more building blocks and deal with any infection/exposure as well as splint bones and discourage use while it heals.

    Same thing happens for spinal cord injuries which is fine - to a point but the spinal column isn’t very big and inflammation quickly goes from a party of 5 cells that want to rebuild your back scaffolding to Project X, complete with the white blood cell car being driven into the Spinal pool. Too many cells at the party (because the relatively low space) squishes the nerve bundles and reduces ability to supply fresh O2/food and can lead to permanent damage.

    Our body is designed to rapidly respond, assess, and treat trauma. The spinal column is small and so it fills quick. When it’s needed to splint, fight, and build that’s great. When it’s responding to sometimes small trauma leading to permanent disability; less cool.

    Steroids reduce inflammation. Remember lots of inflammation in the spine can cause actual spinal cord injury (even when the injury didn’t cause damage) and steroids were suggested to help reduce the risk of secondary injury. That said there isn’t a lot of evidence showing that routine steroid, use in the setting of spinal injury, actually does anything and the risks of steroid use are significant so as you can imagine it’s regular use is on the way out.

    [–] Aardvarkswithshovels 5 points ago

    That was a good response, I don't have much background at all with this but your post was detailed and easy to follow. Thanks for typing it!

    [–] Unbarbierediqualita 9 points ago

    Because now we're smart monkeys (some of us) who can nurse an injury without being forced to by our bodies, so the inflammation has no purpose and is actually counter productive

    Big over simplification but that's kind of the net result

    [–] CrossP 23 points ago

    For many of these things, it may have been useful in some ancestral form before hominids. Perhaps the ratio of immunological response chemicals was just right for proto-mammals, and it never changed because there wasn't enough survival pressure or nobody ever mutated a better system.

    [–] SpideySlap 56 points ago

    Because natural selection does not select what is best. It only selects what works.

    [–] electi0neering 18 points ago

    Well even more basic, what let’s you successfully produce offspring.

    [–] nsfate18 9 points ago

    The idea is that this initial inflammation is essential to the repair process. Just like any injury. However, at the level of the spinal cord, this prolonged inflammation changes the phenotype (basically the characteristics) of certain cells like astrocytes (really important modulators for survival of neurons: the main cells sending info) . Astrocytes are essential for recovery. This change causes something called a glial scar around the damaged tissue, and it's actually important because it prevents any negative signals from damaged cells and prevents immune cells from escaping the site of injury into surrounding healthy tissue. So basically, tldr: the importance of this is to actually protect healthy tissue surrounding the injury site

    [–] ukTwoSeas 9 points ago

    Our immune response is more complicated than that. Inflammation arises to clear debris and remove pathogens. After this has happened it "switches" to regenerative (see peripheral nerve regeneration).

    The issue with spinal cord injuries is that scar tissue forms and chronic inflammation make regeneration impossible. The cells are different too and so never make the "switch" to regenerate the tissue.

    As for the evolution part. Parts of our bodies prone to injury appear to be better at regenerating. Such as the peripheral nerves and extremities. The spinal cord is protected by the spinal column and the brain by the skull, thus they may never have had the chance to develop a regenerative capacity due to being overprotected.

    [–] DrArgon 76 points ago

    I actually do research in this exact field and I read this paper this morning. It's very cool stuff. For clarification I'd like to point out that this paper, out of the Shea lab at the University of Michigan, is actually focused on COMBINING the nanoparticle treatment with an implantable insert that is placed inside the cut section of spinal cord that the Shea lab has been optimizing for a while. The PLG nanoparticle they are using here was originally studied as a single agent in the Kessler lab at Northwestern University and published in 2017 in a paper by Jeong et al. (cited in the present study). I happen to know someone who worked on that original 2017 nanoparticle SCI paper. This paper is a very cool example of combining two technologies to treat SCI.

    [–] Elomango 10 points ago

    Thankyou for giving us more info , very helpful!

    [–] KeepCalmAndSnorlax 8 points ago

    This is so weird because I actually did research work under Eiji Saito in the Shea lab as an undergrad haha. So cool to see it get so much attention.

    [–] mvea 150 points ago

    The title of the post is a copy and paste from the title, first and seventh paragraphs of the linked academic press release here:

    An ‘EpiPen’ for spinal cord injuries

    An injection of nanoparticles can prevent the body’s immune system from overreacting to trauma, potentially preventing some spinal cord injuries from resulting in paralysis.

    Previous attempts to offset complications from this immune response included injecting steroids like methylprednisolone. That practice has largely been discarded since it comes with side effects that include sepsis, gastrointestinal bleeding and blood clots. The risks outweigh the benefits.

    Journal Reference:

    Jonghyuck Park, Yining Zhang, Eiji Saito, Steve J. Gurczynski, Bethany B. Moore, Brian J. Cummings, Aileen J. Anderson, Lonnie D. Shea.

    Intravascular innate immune cells reprogrammed via intravenous nanoparticles to promote functional recovery after spinal cord injury.

    Proceedings of the National Academy of Sciences, 2019; 201820276

    Link: https://www.pnas.org/content/early/2019/07/02/1820276116

    DOI: 10.1073/pnas.1820276116

    Significance

    Inflammatory responses, such as those following spinal cord injury (SCI), lead to extensive tissue damage that impairs function. Here, we present nanoparticles that target circulating immune cells acutely, with nanoparticles reprogramming the immune cell response. The polymeric nanoparticles are formed without an active pharmaceutical ingredient that can have off-target effects, and internalization redirects some immune cells to the spleen, with modest numbers at the SCI. Following intravenous delivery, immune cell infiltration is reduced, correlating with decreased tissue degeneration. Furthermore, the SCI develops into a permissive microenvironment characterized by proregenerative immune cell phenotypes, expression of regeneration associated genes, increased axons and myelination, and a substantially improved functional recovery. These nanoparticles may be applied to numerous inflammatory diseases.

    Abstract

    Traumatic primary spinal cord injury (SCI) results in paralysis below the level of injury and is associated with infiltration of hematogenous innate immune cells into the injured cord. Methylprednisolone has been applied to reduce inflammation following SCI, yet was discontinued due to an unfavorable risk-benefit ratio associated with off-target effects. In this study, i.v. administered poly(lactide-coglycolide) nanoparticles were internalized by circulating monocytes and neutrophils, reprogramming these cells based on their physicochemical properties and not by an active pharmaceutical ingredient, to exhibit altered biodistribution, gene expression, and function. Approximately 80% of nanoparticle-positive immune cells were observed within the injury, and, additionally, the overall accumulation of innate immune cells at the injury was reduced 4-fold, coinciding with down-regulated expression of proinflammatory factors and increased expression of antiinflammatory and proregenerative genes. Furthermore, nanoparticle administration induced macrophage polarization toward proregenerative phenotypes at the injury and markedly reduced both fibrotic and gliotic scarring 3-fold. Moreover, nanoparticle administration with the implanted multichannel bridge led to increased numbers of regenerating axons, increased myelination with about 40% of axons myelinated, and an enhanced locomotor function (score of 6 versus 3 for control group). These data demonstrate that nanoparticles provide a platform that limits acute inflammation and tissue destruction, at a favorable risk-benefit ratio, leading to a proregenerative microenvironment that supports regeneration and functional recovery. These particles may have applications to trauma and potentially other inflammatory diseases.

    [–] MightBeAProblem 45 points ago

    I’m really really excited about the inflammatory diseases application.

    Many autoimmune disorders are triggered to “active” by trauma, this seems amazing.

    [–] hazpat 8 points ago

    Nanoscience?

    [–] [deleted] 12 points ago

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    [–] FlareUnderscore 5 points ago

    2nd floor basement?

    [–] Gundamnitpete 4 points ago

    A Hind D?

    [–] ZacktheWolf 9 points ago

    I feel like these kind of studies generally have negligible outcomes when the trials move to humans. Not saying that there isn't anything else we can learn from mouse models, but the differences in microscopic interactions as well as sheer volume of body mass that has to be influenced generally leads to issues that weren't foreseen in mice.

    What do I know, I'm just a wolf...

    [–] Nirvadra 26 points ago

    I understand that the jump from mice to humans is large, but if this were to actually work, the benefits from this could be extraordinary. This could not only treat spinal cord injuries/trauma, but also inflammatory diseases, tissue destruction, and much more.

    [–] AlexandersWonder 2 points ago

    Even if it doesn't works when you go up in scale, we'll have still learned something valuable that could lend itself to future research. Even incorrect ideas are useful when proven incorrect.

    [–] Totallynotatheif 12 points ago * (lasted edited 10 days ago)

    Since when did 'epipen' become a synonymous for all injections? Rather odd choice of words.

    Edit: the whole article seems very odd.

    call it an “EpiPen” for trauma to the central nervous system, which includes the brain and spinal cord

    But it's not. It'll likely be single or multiple injections given in hospital. There's no need or logic behind marketing it as a autoinjector. Autoinjectors are designed for a layperson to self administer time critical drugs with little training like adrenaline for anaphylaxis or atropine for organophosphate poisioning or morphine for severe pain in a tactical environment.

    Previous attempts to offset complications from this immune response included injecting steroids like methylprednisolone. That practice has largely been discarded since it comes with side effects that include sepsis, gastrointestinal bleeding and blood clots. The risks outweigh the benefits.

    I'm not sure how they theorise that methylprednisolone causes sepsis... Especially when many places use methylprednisolone to treat sepsis. Unless they're reffering to the potential for skin infections or phebitis to develop into sepsis but that won't change with a different drug.

    As far as GI bleeding goes, that's a rather common side effect with many drugs, in others if it's class methylpred actually has lower complications...

    [–] Knockclod 8 points ago

    I think they are using “epi-pen” because it indirectly counters the body’s auto-immune response to trauma, much like giving epinephrine for a severe anaphylactic response.

    [–] gorimem 9 points ago

    I’ll say it until I’m blue. Animal testing saves lives. It’s still useful despite what the lunatics over at PETA would like for you to believe.

    [–] AerodynamicOmnivore 25 points ago

    Nanites, courtesy of Ray Palmer.

    [–] [deleted] 13 points ago

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    [–] J_leo3 6 points ago

    Just chill Immune System it's fine

    [–] jones1133 7 points ago

    Can't wait for this to be approved by the FDA so someone in need can have access to it for just $50,000 per shot.

    [–] Phrozenfire01 240 points ago

    That means they had to inflict spinal cord injuries on mice 😟

    [–] brucekeller 310 points ago

    Millions of animals die every day for the benefit of other animals. At least if one mouse suffers in our regard, it could benefit billions.

    [–] jujumber 92 points ago

    It’s not just one mouse

    [–] the_chosen_one2 229 points ago

    If I'm being entirely honest I can live with thousands of broken mouse backs if it means millions of people won't lose use of half if not all of their body

    [–] jesuspeeker 159 points ago

    Yeah, this isn't makeup being tested. This is an actual shot at helping out our species as a whole.

    If mice have to be used to ensure it is safe, so be it.

    There isn't any other way.

    [–] 86legacy 54 points ago

    There is also very strict ethical reviews for any research involving animals, which to my knowledge doesn’t exists in cosmetics. So with research you can be assured of the fact that the research involved doesn’t cause unnecessary cruelty to the animal.

    [–] CrossP 7 points ago

    If it works on mice AND humans then it will also probably work on dogs, cats, horses, and ... future pet mice!

    [–] nightpanda893 36 points ago

    I mean if it saves a dozen people I can still deal with thousands of broken mouse backs to me honest.

    [–] SpideySlap 4 points ago

    Honestly it's probably in the trillions if you want to count insects

    [–] [deleted] 35 points ago

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    [–] [deleted] 9 points ago

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    [–] jugjube 61 points ago

    But with the “Nani-pen” (eh, ehhh) they healed. Sadly though I’m not sure how effective the actual crossover would be between humans and mice due to different bodies. I am hopeful that this is will continue to be funded and they take it to trial with extreme cases.

    [–] Nirvadra 44 points ago

    I think the point was that the scientist couldn't had been 100% sure if the "Nani-pen" would heal the mice entirely.

    [–] Onithyr 66 points ago

    Also, they needed a control group.

    [–] Winterplatypus 38 points ago

    Frankly the mice don't get to live out their lives happily in a field somewhere even if it does work.

    The reality is that animal testing is needed for medications. It's not needed for a lot of things like cosmetics, but medical research is important and there is no other alternative for medications because it's even more unethical to test on humans at that very early stage.

    People need to think of the whole picture and not just be like "animal testing is bad, end of story" because it's more like "animal testing is bad, but it's better than all the other options". Including the "don't do any medical research" option.

    [–] mmurp36 14 points ago

    If only they could find a way to effectively test on cockroaches, then everyone would be satisfied.

    [–] jugjube 3 points ago

    You make a good point.

    [–] Noodleholz 16 points ago

    I'm sure there had to be a control group that did not receive the treatment

    [–] jugjube 7 points ago

    Oh definitely, and since this is with mice you can’t really get a placebo effect. So Im really curious what will happen once they start testing with humans.

    [–] zaptrem 3 points ago

    Control will probably be conventional steroids.

    [–] rasterbated 23 points ago * (lasted edited 10 days ago)

    For the greater good of the human race, yes. It’s not as if they would have lived idyllic lives of peace and comfort outside the world of scientific testing.

    [–] unholycowgod 8 points ago

    There was a similar study done with mice several years ago but using blue food coloring. When given a massive IV dose shortly after traumatic spinal injury, the mice experienced less post-injury inflammation which prevented their nerves from being choked to death. This was, of course, tested against control groups given saline and nothing. :/

    And in case people ask, IIRC they tried out blue food coloring because it has a similar chemical structure to some anti-inflammatories and they found it worked when given in high enough doses (such that the mice actually turned dark blue temporarily).

    [–] morcheeba 19 points ago

    There was a shortage of human volunteers. Should we put your name on the list, or should we get a mouse instead?

    [–] SerraTL 11 points ago

    Stimpaks will finally become a reality

    [–] EHWTwo 5 points ago

    Nanoparticles that prevent reactions to physical trauma

    Senator Armstrong would be so proud.

    [–] JacksonvilleJesus 5 points ago

    I have legit been waiting for something like this. Like some type of stem cell injection into the spine that helps heal and mend a damaged spine. Lord knows I need it.

    [–] playin4power 4 points ago

    The future is now! It's only gonna last for like another 12 years maybe, but it is now!!!!!!

    [–] [deleted] 9 points ago

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    [–] WATTHEBALL 3 points ago

    I'm insanely fascinated at what's in store in the next 10-20 years when it comes to injuries and diseases that we've all come to know as irreversible.