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Agglomeration of preclinical and clinical evidence in recent years specified that alterations in neural networks favor certain characteristics of PTSD. Besides the disruption of hypothalamus-pituitary-axis (HPA) axis, intensified immune status with elevated pro-inflammatory cytokines and arachidonic metabolites of COX-2 such as PGE2 creates a putative scenario in worsening the neurobehavioral facet of PTSD. This review aims to link the Diagnostic and Statistical Manual of mental disorders (DSM-V) symptomology to major neural mechanisms that are supposed to underpin the transition from acute stress reactions to the development of PTSD. Also, to demonstrate how these intertwined processes can be applied to probable early intervention strategies followed by a description of the evidence supporting the proposed mechanisms. Hence in this review, several neural network mechanisms were postulated concerning the HPA axis, COX-2, PGE2, NLRP3, and sirtuins to unravel possible complex neuroinflammatory mechanisms that are obscured in PTSD condition.<\/jats:p>","DOI":"10.1007\/s11481-023-10064-z","type":"journal-article","created":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T07:02:55Z","timestamp":1682406175000},"page":"248-266","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Emphasizing the Crosstalk Between Inflammatory and Neural Signaling in Post-traumatic Stress Disorder (PTSD)"],"prefix":"10.1007","volume":"18","author":[{"given":"Anusha","family":"Govindula","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niraja","family":"Ranadive","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhavan","family":"Nampoothiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C Mallikarjuna","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7106-7769","authenticated-orcid":false,"given":"Devinder","family":"Arora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8190-7031","authenticated-orcid":false,"given":"Jayesh","family":"Mudgal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,4,25]]},"reference":[{"key":"10064_CR1","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1016\/j.psyneuen.2009.05.003","volume":"34","author":"B Aisa","year":"2009","unstructured":"Aisa B, Gil-Bea FJ, Marcos B et al (2009) Neonatal stress affects vulnerability of cholinergic neurons and cognition in the rat: involvement of the HPA axis. 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