{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:42:20Z","timestamp":1788273740047,"version":"build-2803163510"},"reference-count":157,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T00:00:00Z","timestamp":1628208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000073","name":"Autism Speaks","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000073","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["P30ES030283"],"award-info":[{"award-number":["P30ES030283"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Autism Spectrum Disorder (ASD) is a neurodevelopmental disease originating from combined genetic and environmental factors. Post\u2010mortem human studies and some animal ASD models have shown brain neuroinflammation, oxidative stress, and changes in blood\u2013brain barrier (BBB) integrity. However, the signaling pathways leading to these inflammatory findings and vascular alterations are currently unclear. The BBB plays a critical role in controlling brain homeostasis and immune response. Its dysfunction can result from developmental genetic abnormalities or neuroinflammatory processes. In this review, we explore the role of the Sonic Hedgehog\/Wingless\u2010related integration site (Shh\/Wnt) pathways in neurodevelopment, neuroinflammation, and BBB development. The balance between Wnt\u2010\u03b2\u2010catenin and Shh pathways controls angiogenesis, barriergenesis, neurodevelopment, central nervous system (CNS) morphogenesis, and neuronal guidance. These interactions are critical to maintain BBB function in the mature CNS to prevent the influx of pathogens and inflammatory cells. Genetic mutations of key components of these pathways have been identified in ASD patients and animal models, which correlate with the severity of ASD symptoms. Disruption of the Shh\/Wnt crosstalk may therefore compromise BBB development and function. In turn, impaired Shh signaling and glial activation may cause neuroinflammation that could disrupt the BBB. Elucidating how ASD\u2010related mutations of Shh\/Wnt signaling could cause BBB leaks and neuroinflammation will contribute to our understanding of the role of their interactions in ASD pathophysiology. These observations may provide novel targeted therapeutic strategies to prevent or alleviate ASD symptoms while preserving normal developmental processes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15460-fig-0004-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:bold>Cover Image for this issue:<\/jats:bold>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/doi.org\/10.1111\/jnc.15081\">https:\/\/doi.org\/10.1111\/jnc.15081<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jnc.15460","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T04:51:36Z","timestamp":1624596696000},"page":"15-28","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Potential crosstalk between sonic hedgehog\u2010WNT signaling and neurovascular molecules: Implications for blood\u2013brain barrier integrity in autism spectrum disorder"],"prefix":"10.1111","volume":"159","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7451-087X","authenticated-orcid":false,"given":"Evelyne","family":"Gozal","sequence":"first","affiliation":[{"name":"Department of Pediatrics Pediatric Research Institute University of Louisville Louisville KY 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