Traumatic Injury Leads to Inflammation and Altered Tryptophan Metabolism in the Juvenile Rabbit Brain

Research output: Contribution to journalArticle

Abstract

Neuroinflammation after traumatic brain injury (TBI) contributes to widespread cell death and tissue loss. Here, we evaluated sequential inflammatory response in the brain, as well as inflammation-induced changes in brain tryptophan metabolism over time, in a rabbit pediatric TBI model. On post-natal days 5-7 (P5-P7), New Zealand white rabbit littermates were randomized into three groups: naïve (no injury), sham (craniotomy alone), and TBI (controlled cortical impact). Animals were sacrificed at 6 h and 1, 3, 7, and 21 days post-injury for evaluating levels of pro- and anti-inflammatory cytokines, as well as the major components in the tryptophan-kynurenine pathway. We found that 1) pro- and anti-inflammatory cytokine levels in the brain injury area were differentially regulated in a time-dependent manner post-injury; 2) indoleamine 2,3 dioxygeenase 1 (IDO1) was upregulated around the injury area in TBI kits that persisted at 21 days post-injury; 3) mean length of serotonin-staining fibers was significantly reduced in the injured brain region in TBI kits for at least 21 days post-injury; and 4) kynurenine level significantly increased at 7 days post-injury. A significant decrease in serotonin/tryptophan ratio and melatonin/tryptophan ratio at 21 days post-injury was noted, suggesting that tryptophan metabolism is altered after TBI. A better understanding of the temporal evolution of immune responses and tryptophan metabolism during injury and repair after TBI is crucial for the development of novel therapeutic strategies targeting these pathways.

Original languageEnglish (US)
Pages (from-to)74-86
Number of pages13
JournalJournal of Neurotrauma
Volume36
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Tryptophan
Rabbits
Inflammation
Wounds and Injuries
Brain
Kynurenine
Serotonin
Anti-Inflammatory Agents
Cytokines
Craniotomy
Melatonin
Traumatic Brain Injury
Brain Injuries
Cell Death
Pediatrics
Staining and Labeling

Keywords

  • IDO
  • inflammation
  • microglia
  • serotonin
  • TBI

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

@article{cff9a26be1c04d249834044155c10fd4,
title = "Traumatic Injury Leads to Inflammation and Altered Tryptophan Metabolism in the Juvenile Rabbit Brain",
abstract = "Neuroinflammation after traumatic brain injury (TBI) contributes to widespread cell death and tissue loss. Here, we evaluated sequential inflammatory response in the brain, as well as inflammation-induced changes in brain tryptophan metabolism over time, in a rabbit pediatric TBI model. On post-natal days 5-7 (P5-P7), New Zealand white rabbit littermates were randomized into three groups: na{\"i}ve (no injury), sham (craniotomy alone), and TBI (controlled cortical impact). Animals were sacrificed at 6 h and 1, 3, 7, and 21 days post-injury for evaluating levels of pro- and anti-inflammatory cytokines, as well as the major components in the tryptophan-kynurenine pathway. We found that 1) pro- and anti-inflammatory cytokine levels in the brain injury area were differentially regulated in a time-dependent manner post-injury; 2) indoleamine 2,3 dioxygeenase 1 (IDO1) was upregulated around the injury area in TBI kits that persisted at 21 days post-injury; 3) mean length of serotonin-staining fibers was significantly reduced in the injured brain region in TBI kits for at least 21 days post-injury; and 4) kynurenine level significantly increased at 7 days post-injury. A significant decrease in serotonin/tryptophan ratio and melatonin/tryptophan ratio at 21 days post-injury was noted, suggesting that tryptophan metabolism is altered after TBI. A better understanding of the temporal evolution of immune responses and tryptophan metabolism during injury and repair after TBI is crucial for the development of novel therapeutic strategies targeting these pathways.",
keywords = "IDO, inflammation, microglia, serotonin, TBI",
author = "Zhi Zhang and Lindsey Rasmussen and Manda Saraswati and Koehler, {Raymond C} and Courtney Robertson and Sujatha Kannan",
year = "2019",
month = "1",
day = "1",
doi = "10.1089/neu.2017.5450",
language = "English (US)",
volume = "36",
pages = "74--86",
journal = "Journal of Neurotrauma",
issn = "0897-7151",
publisher = "Mary Ann Liebert Inc.",
number = "1",

}

TY - JOUR

T1 - Traumatic Injury Leads to Inflammation and Altered Tryptophan Metabolism in the Juvenile Rabbit Brain

AU - Zhang, Zhi

AU - Rasmussen, Lindsey

AU - Saraswati, Manda

AU - Koehler, Raymond C

AU - Robertson, Courtney

AU - Kannan, Sujatha

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Neuroinflammation after traumatic brain injury (TBI) contributes to widespread cell death and tissue loss. Here, we evaluated sequential inflammatory response in the brain, as well as inflammation-induced changes in brain tryptophan metabolism over time, in a rabbit pediatric TBI model. On post-natal days 5-7 (P5-P7), New Zealand white rabbit littermates were randomized into three groups: naïve (no injury), sham (craniotomy alone), and TBI (controlled cortical impact). Animals were sacrificed at 6 h and 1, 3, 7, and 21 days post-injury for evaluating levels of pro- and anti-inflammatory cytokines, as well as the major components in the tryptophan-kynurenine pathway. We found that 1) pro- and anti-inflammatory cytokine levels in the brain injury area were differentially regulated in a time-dependent manner post-injury; 2) indoleamine 2,3 dioxygeenase 1 (IDO1) was upregulated around the injury area in TBI kits that persisted at 21 days post-injury; 3) mean length of serotonin-staining fibers was significantly reduced in the injured brain region in TBI kits for at least 21 days post-injury; and 4) kynurenine level significantly increased at 7 days post-injury. A significant decrease in serotonin/tryptophan ratio and melatonin/tryptophan ratio at 21 days post-injury was noted, suggesting that tryptophan metabolism is altered after TBI. A better understanding of the temporal evolution of immune responses and tryptophan metabolism during injury and repair after TBI is crucial for the development of novel therapeutic strategies targeting these pathways.

AB - Neuroinflammation after traumatic brain injury (TBI) contributes to widespread cell death and tissue loss. Here, we evaluated sequential inflammatory response in the brain, as well as inflammation-induced changes in brain tryptophan metabolism over time, in a rabbit pediatric TBI model. On post-natal days 5-7 (P5-P7), New Zealand white rabbit littermates were randomized into three groups: naïve (no injury), sham (craniotomy alone), and TBI (controlled cortical impact). Animals were sacrificed at 6 h and 1, 3, 7, and 21 days post-injury for evaluating levels of pro- and anti-inflammatory cytokines, as well as the major components in the tryptophan-kynurenine pathway. We found that 1) pro- and anti-inflammatory cytokine levels in the brain injury area were differentially regulated in a time-dependent manner post-injury; 2) indoleamine 2,3 dioxygeenase 1 (IDO1) was upregulated around the injury area in TBI kits that persisted at 21 days post-injury; 3) mean length of serotonin-staining fibers was significantly reduced in the injured brain region in TBI kits for at least 21 days post-injury; and 4) kynurenine level significantly increased at 7 days post-injury. A significant decrease in serotonin/tryptophan ratio and melatonin/tryptophan ratio at 21 days post-injury was noted, suggesting that tryptophan metabolism is altered after TBI. A better understanding of the temporal evolution of immune responses and tryptophan metabolism during injury and repair after TBI is crucial for the development of novel therapeutic strategies targeting these pathways.

KW - IDO

KW - inflammation

KW - microglia

KW - serotonin

KW - TBI

UR - http://www.scopus.com/inward/record.url?scp=85059084517&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059084517&partnerID=8YFLogxK

U2 - 10.1089/neu.2017.5450

DO - 10.1089/neu.2017.5450

M3 - Article

C2 - 30019623

AN - SCOPUS:85059084517

VL - 36

SP - 74

EP - 86

JO - Journal of Neurotrauma

JF - Journal of Neurotrauma

SN - 0897-7151

IS - 1

ER -