Looking at the Brain of PANDAS and PANS Children

looking at the brains of pandas and Pan's children how peripheral infection triggers brain inflammation this animation will show you some of the new research conducted by several research Labs related to the diagnosis and treatment of pandas and pans which was made possible by the generous donations of pandas Network families this science shows the imperative of early diagnosis and treatment for this complex patient population in order to prevent Progressive brain damage pediatric autoimmune Neuropsychiatric disorders associated with streptococcal infection or pandas and pediatric acute onset Neuropsychiatric syndrome or pans are a group of related autoimmune or autoinflammatory disorders that affect the central nervous system or CNS these disorders are triggered by infections either bacterial viral or fungal they occur when the body's immune system inappropriately attacks healthy brain tissue triggering neurological and or psychiatric symptoms post-infectious responses in pandas and pans primarily affect the region of the brain known as the basal ganglia the basal ganglia are a group of interconnected structures within the brain that are associated with regulating functions such as motor movement cognitive and emotional response and procedural learning as a consequence pandas and pans are characterized primarily by an Abrupt onset of abnormal movement and or psychiatric symptoms how do peripheral bacterial or viral infections cause brain inflammation repeated exposure to an infectious agent such as group a Streptococcus or group a strep or viruses like covid-19 cause the body to launch an immune response against the Infectious agent the body produces antibodies to fight the invading infection however in certain patients this immune response leads to the production of abnormal antibodies known as autoantibodies which attack the host's own healthy brain cells how these Auto antibodies enter the brain is not well understood however Recent research in both mice and pandas children may provide an answer in the mouth disease model for pandas and pans repeated group a strep infections of the mucous membrane in the upper nasal cavity lead to the production and accumulation of th17 and th1 lymphocytes in the surrounding tissue th17 and th1 lymphocytes are pro-inflammatory immune cells that are generated to fight the bacterial infection however in many autoimmune diseases these cells may cause a misdirected immune response that targets the host's own healthy cells research studies in mice suggest that th17 lymphocytes May travel along the nerves that sense smells called olfactory nerves from the nose to the brain once in the brain th17 cells release inflammatory cytokines that are important for immune cell communication these cytokines also stimulate specialized immune cells of the CNS called microglia which release their own inflammatory cytokines in addition to microglial activation th17 lymphocytes release two pro-inflammatory cytokines called il17a and gmcsf which trigger the breakdown of the blood-brain barrier or BBB the BBB is a highly selective semi-permeable boundary of specialized cells known as endothelial cells that line the blood vessels of the brain and prevent molecules in the circulating blood from indiscriminately entering the brain these inflammatory cytokines caused the BBB to break down in two ways first they damaged the tight Junction or TJ proteins of the endothelial cells TJ proteins join the endothelial cells of the BBB to one another and prevent the transport of molecules from the blood to the brain the second way in which the cytokines break down the BBB is by increasing transitosis or the transport of molecules within endothelial cells and into the brain how is this relevant to pandas and pans the damage to tight junctions and the increase in endothelial transcytosis allows potential Auto antibodies circulating in the blood to enter the brain where they can cause further damage recent work from Yale University with pandas and Pan's children has shown that once these Auto antibodies crossed the BBB they attack a group of neurons in the basal ganglia called cholinergic interneurons that are important for movement and mood in addition work from the University of Oklahoma has suggested these antibodies interact with dopamine receptors in the basal ganglia triggering their abnormal activation and causing mood and movement disorders recent studies in the mouse model have further demonstrated that blocking il-17a function does not prevent the entry of th17 lymphocytes into the brain however this treatment is very effective in blocking the activation of microglia and preventing blood-brain barrier damage improving disease outcomes therefore therapies that Target il-17a may prove beneficial in children suffering from pandas and pans human Studies have identified that a set of pro-inflammatory cytokines are highly elevated in pandas and Pan's children at the acute phase of the disease additionally these pro-inflammatory cytokines are able to break down the BBB in research experiments this implies that they may potentially trigger BBB breakdown in patients this is the first study that has identified th17 lymphocytes and cytokines il-17a NGM CSF does major players and causing the breakdown of the BBB after repeated group a strep infections in mice additional studies are currently underway to examine the role of th17 cells or other immune cells in humans suffering from pandas and pans in order to improve the diagnosis of these CNS disorders it is imperative to develop biomarkers that can be used to test for the disease these tests can range from analysis of cerebrospinal fluid blood tests for inflammatory cytokines and using Dynamic contrast enhanced MRI imaging tools to detect BBB breakdown during flare-ups of the disease existing therapies that Target il-17a have already been developed and are being used to treat certain autoimmune diseases these therapies may prove beneficial in children suffering from pandas and pans the findings from the mouth studies indicate that there is previously undiscovered communication between the CNS and adaptive cellular immunity to infections this may help lead to understanding how many other CNS autoimmune disorders develop such as sydnum's Korea a disease related to pandas and pans multiple sclerosis nmdar Encephalitis and long covid additionally these findings support the need for early identification of pandas and pans cases and the critical role of immune modulating Therapies in treating these disorders thank you for watching we hope this has shed light on the mechanisms in a difficult CNS disease groundbreaking research and treatment protocols will continue to be published please stay tuned for the latest developments

Channel: PANDAS Network Official

Views: 22,071

Keywords: pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, pediatric autoimmune neuropsychiatric, pediatric autoimmune neuropsychiatric disorders, paediatric autoimmune neuropsychiatric disorder, pediatric autoimmune neuropsychiatric disorder (panda), autoimmune, pediatric acute-onset neuropsychiatric syndrome (pans), pediatric autoimmune neuropsychiatric disorder, pediatric autoimmune neuropsychiatric disorder associated with strep infections

Id: WzA1Pw1xwqM

Length: 8min 23sec (503 seconds)

Published: Tue Mar 28 2023