MSGID: 1:317/3 640960f9   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
   surgical treatment    
    A noninvasive way to avoid the repeat failures of shunt placement in   
   patients with hydrocephalus has been the holy grail of scientists in the field   
      
      
     Date:   
         March 8, 2023   
     Source:   
         Massachusetts General Hospital   
     Summary:   
         Researchers have learned that the same molecular pathway is   
         involved in both the infectious and hemorrhagic forms of acquired   
         hydrocephalus, a life-threatening disease that triggers a massive   
         neuroinflammatory response and swelling of the ventricles of   
         the brain.   
      
      
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   FULL STORY   
   ==========================================================================   
   Mass General researchers have discovered a novel molecular mechanism   
   responsible for the most common forms of acquired hydrocephalus,   
   potentially opening the door to the first-ever nonsurgical treatment for   
   a life-threatening disease that affects about a million Americans. As   
   reported in the journal Cell, the team uncovered in animal models the   
   pathway through which infection or bleeding in the brain triggers a   
   massive neuroinflammatory response that results in increased production   
   of cerebrospinal fluid (CSF) by tissue known as the choroid plexus,   
   leading to swelling of the brain ventricles.   
      
      
   ==========================================================================   
   "Finding a nonsurgical treatment for hydrocephalus, given the fact   
   neurosurgery is fraught with tremendous morbidity and complications,   
   has been the holy grail for our field," says Kristopher Kahle, MD, PhD,   
   a pediatric neurosurgeon at MGH and senior author of the study. "We've   
   identified through a genome-wide analytical approach the mechanism that   
   underlies the swelling of the ventricles which occurs after a brain   
   bleed or brain infection in acquired hydrocephalus.   
      
   We're hopeful these findings will pave the way for approval of an anti-   
   inflammatory drug to treat hydrocephalus, which could be a game-changer   
   for populations in the U.S. and around the world that don't have   
   access to surgery."  Acquired hydrocephalus occurs in about one of   
   every 500 births globally. It is the most common cause of brain surgery   
   in children, though it can affect people at any age. In underdeveloped   
   parts of the world where bacterial infection is the most prevalent form   
   of the disease, hydrocephalus is often deadly for children due to the   
   lack of surgical intervention. Indeed, the only known treatment for   
   acquired hydrocephalus is brain surgery, which involves implantation   
   of a catheter-like shunt to drain fluid from the brain. But about half   
   of all shunts in pediatric patients fail within two years of placement,   
   according to the Hydrocephalus Association, requiring repeat neurosurgical   
   operations and a lifetime of brain surgeries.   
      
   By deciphering the unique cellular and molecular biology that occurs   
   within the brain after infection or severe hemorrhage, the MGH-led   
   research team has taken a major step toward nonsurgical, pharmacologic   
   treatment for humans. Pivotal to the process is the choroid plexus, the   
   brain structure that routinely pumps cerebrospinal fluid into the four   
   ventricles of the brain to keep the organ buoyant and injury-free within   
   the skull. An infection or brain bleed, however, can create a dangerous   
   neuroinflammatory response where the choroid plexus floods the ventricles   
   with cerebral spinal fluid and immune cells from the periphery of the   
   brain -- a so-called "cytokine storm," or immune system overreaction,   
   so often seen in COVID-19 infections -- swelling the brain ventricles.   
      
   "Scientists in the past thought that entirely different mechanisms were   
   involved in hydrocephalus from infection and from hemorrhage in the   
   brain," explains co-author Bob Carter, MD, PhD, chair of the Department   
   of Neurosurgery at MGH. "Dr. Kahle's lab found that the same pathway was   
   involved in both types and that it can be targeted with immunomodulators   
   like rapamycin, a drug that's been approved by the U.S. Food and Drug   
   Administration for transplant patients who need to suppress their immune   
   system to prevent organ rejection."  MGH researchers are continuing   
   to explore how rapamycin and other repurposed drugs which quell the   
   inflammation seen in acquired hydrocephalus could be turned into an   
   effective drug treatment for patients. "What has me most excited is that   
   this noninvasive therapy could provide a way to help young patients who   
   don't have access to neurosurgeons or shunts," emphasizes Kahle. "No   
   longer would a diagnosis of hydrocephalus be fatal for these children."   
   Kahle is director of Pediatric Neurosurgery at MGH, and director of the   
   Harvard Center for Hydrocephalus and Neurodevelopmental Disorders. Carter   
   is chief of Neurosurgery Service at MGH and professor of Surgery at   
   Harvard Medical School.   
      
   The study was funded by the National Institutes of Health and the   
   Hydrocephalus Association.   
      
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                   # Brain_Tumor # Birth_Defects # Nervous_System #   
                   Diseases_and_Conditions   
             o Mind_&_Brain   
                   # Brain-Computer_Interfaces # Brain_Injury # Neuroscience   
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             o Inflammation o Ebola o Allergy o Molecular_biology o   
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   ==========================================================================   
   Story Source: Materials provided by Massachusetts_General_Hospital. Note:   
   Content may be edited for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Stephanie M. Robert, Benjamin C. Reeves, Emre Kiziltug, Phan Q. Duy,   
         Jason K. Karimy, M. Shahid Mansuri, Arnaud Marlier, Garrett   
         Allington, Ana B.W. Greenberg, Tyrone DeSpenza, Amrita K. Singh,   
         Xue Zeng, Kedous Y.   
      
         Mekbib, Adam J. Kundishora, Carol Nelson-Williams, Le Thi Hao,   
         Jinwei Zhang, TuKiet T. Lam, Rashaun Wilson, William E. Butler,   
         Michael L.   
      
         Diluna, Philip Feinberg, Dorothy P. Schafer, Kiavash Movahedi, Allen   
         Tannenbaum, Sunil Koundal, Xinan Chen, Helene Benveniste, David D.   
      
         Limbrick, Steven J. Schiff, Bob S. Carter, Murat Gunel,   
         J. Marc Simard, Richard P. Lifton, Seth L. Alper, Eric Delpire,   
         Kristopher T. Kahle. The choroid plexus links innate immunity to   
         CSF dysregulation in hydrocephalus. Cell, 2023; 186 (4): 764 DOI:   
         10.1016/j.cell.2023.01.017   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2023/03/230308112221.htm   
      
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