Systemic inflammation following non-cranial trauma and its impact on neuroinflammatory-neurodegenerative gene expression in the rodent brain

Cassie Rowe, Uloma Nwaolu, Laura Martin, Benjamin Huang, Josef Mang, Daniela Salinas, Cody D. Schlaff, Sennay Ghenbot, Jefferson L. Lansford, Benjamin K Potter, Seth Schobel-McHugh, Eric Gann, Thomas Davis

Research output: Contribution to specialist publicationArticle

Abstract

Trauma can result in systemic inflammation that leads to organ dysfunction, but the
impact on the brain, particularly following non-cranial traumatic insults, has been
largely overlooked. Building upon our prior findings, we aimed to understand the
impact of trauma-induced inflammation on the neuroinflammatory-neurodegenerative
transcription in eight brain regions using rats exposed to (1) blast overpressure exposure [BOP], (2) cutaneous thermal injury [BU], (3) complex extremity injury, three hours
of tourniquet-induced ischemia, and hind limb amputation [CEI+tI+HLA], (4)
BOP+BU or (5) BOP+CEI and delayed HLA [BOP+CEI+dHLA] at 6, 24, and 168 hours
post-injury (hpi). Globally, the number and magnitude of differentially expressed genes
(DEGs) correlated with injury severity, markers systemic inflammation, and end organ
damage, driven by several chemokines/cytokines (Csf3, Cxcr2, Il16, Tgfb2),
neurosteroids/prostaglandins (Cyp19a1, Ptger2, Ptger3), and markers of
neurodegeneration (Gfap, Grin2b, Homer1). Regional neuroinflammatory activity was
least impacted following BOP. Non-cranial trauma (BU and CEI+tI+HLA groups)
contributed to an earlier, robust and diverse neuroinflammatory response across brain
regions (up 2-50-fold from BOP), while combined trauma (BOP+CEI+dHLA)
significantly advanced neuroinflammation in all regions except for the cerebellum. In
contrast, BOP+BU resulted in differential activity of several critical neuroinflammatory-neurodegenerative markers compared to BU. t-SNE plots of DEGs demonstrated the
onset, extent, and duration of the inflammatory response is brain region-dependent.
Irrespective of injury type, the hypothalamus and thalamus – critical for maintaining
homeostasis – resulted in the most DEGs. Our results indicate that neuroinflammation
in all groups progressively increased or remained at peak levels over the study
duration, while markers of end-organ dysfunction decreased or otherwise resolved.
Collectively, these findings emphasize the brain's sensitivity to mediators of systemic
inflammation and an example of immune-brain crosstalk. Molecular and behavioral
investigations are warranted to understand the short-long-term pathophysiological
consequences on the brain, in particular mechanism of blood-brain barrier breakdown,
immune cell penetration-activation, and microglial activation.
Original languageAmerican English
Specialist publicationJournal of Neuroinflammation
StateSubmitted - 1 Apr 2024

Fingerprint

Dive into the research topics of 'Systemic inflammation following non-cranial trauma and its impact on neuroinflammatory-neurodegenerative gene expression in the rodent brain'. Together they form a unique fingerprint.

Cite this