{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T05:44:21Z","timestamp":1793598261968,"version":"4.5.0"},"posted":{"date-parts":[[2025,9,7]]},"group-title":"Physiology","reference-count":39,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T00:00:00Z","timestamp":1757203200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["T32-HL091816"],"award-info":[{"award-number":["T32-HL091816"]}],"id":[{"id":"https:\/\/ror.org\/023ny1p48","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01HL160138"],"award-info":[{"award-number":["R01HL160138"]}],"id":[{"id":"https:\/\/ror.org\/023ny1p48","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01HL127342"],"award-info":[{"award-number":["R01HL127342"]}],"id":[{"id":"https:\/\/ror.org\/023ny1p48","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01HL111656"],"award-info":[{"award-number":["R01HL111656"]}],"id":[{"id":"https:\/\/ror.org\/023ny1p48","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01HL158108"],"award-info":[{"award-number":["R01HL158108"]}],"id":[{"id":"https:\/\/ror.org\/023ny1p48","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["24CDA1274310"],"award-info":[{"award-number":["24CDA1274310"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Pulmonary arterial hypertension (PAH) is associated with neurocognitive deficits and abnormal brain MRI. Little is known about the mechanisms underlying these clinical observations. TDP-43 is a proteinopathy associated with frontotemporal lobar degeneration (FTLD), Alzheimer\u2019s Disease, and Amyotrophic Lateral Sclerosis (ALS). In this study, we hypothesize PAH will result in gliosis, reduced neuronal density, and increased TDP-43 mislocalization.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Sprague Dawley rats were randomly assigned to receive Vehicle (DMSO) Monocrotaline, or Sugen\/Hypoxia to induce PH. Right heart catheterization was used to confirm PAH. Brain tissue was fixed and probed for microglia (Iba1), astrocytes (GFAP), neurons (NeuN), and TDP-43. Human PH vs control brain tissue was also probed for NeuN and TDP-43.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results and Conclusions<\/jats:title>\n                  <jats:p>We identify an increase in microglia and astrocyte density in the frontal cortex along with reduced neuronal density and neuronal TDP-43 mislocalization in rat models of PH. In addition, human PH frontal cortex demonstrated neuronal TDP-43 mislocalization. This is the first evidence of TDP-43 proteinopathy in PH.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.09.02.673803","type":"posted-content","created":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T16:05:13Z","timestamp":1757261113000},"source":"Crossref","is-referenced-by-count":2,"title":["Pulmonary Hypertension Promotes Neuroinflammation and Neurodegeneration"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4620-9769","authenticated-orcid":false,"given":"Priscilla M.","family":"De La Cruz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelia","family":"Lockett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta T.","family":"Gomes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somanshu","family":"Banerjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asif","family":"Razee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Fisher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D.","family":"Lloyd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shino","family":"Magaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8036-3079","authenticated-orcid":false,"given":"Soban","family":"Umar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian L.","family":"Oblak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto F.","family":"Machado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025091105200629000_2025.09.02.673803v2.1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(15)00543-3"},{"key":"2025091105200629000_2025.09.02.673803v2.2","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51867"},{"key":"2025091105200629000_2025.09.02.673803v2.3","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-7-55"},{"key":"2025091105200629000_2025.09.02.673803v2.4","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202204-0726LE"},{"key":"2025091105200629000_2025.09.02.673803v2.5","doi-asserted-by":"publisher","DOI":"10.1111\/jon.12840"},{"key":"2025091105200629000_2025.09.02.673803v2.6","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.118.10934"},{"key":"2025091105200629000_2025.09.02.673803v2.7","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.122.20782"},{"key":"2025091105200629000_2025.09.02.673803v2.8","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-020-00513-7"},{"key":"2025091105200629000_2025.09.02.673803v2.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-020-00537-7"},{"key":"2025091105200629000_2025.09.02.673803v2.10","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ads0505"},{"key":"2025091105200629000_2025.09.02.673803v2.11","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1350-y"},{"key":"2025091105200629000_2025.09.02.673803v2.12","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-023-01625-7"},{"key":"2025091105200629000_2025.09.02.673803v2.13","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232314516"},{"key":"2025091105200629000_2025.09.02.673803v2.14","doi-asserted-by":"publisher","DOI":"10.3791\/52434"},{"key":"2025091105200629000_2025.09.02.673803v2.15","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-48077-6"},{"key":"2025091105200629000_2025.09.02.673803v2.16","unstructured":"R: The R Project for Statistical Computing. 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