Acute, regional inflammatory response after traumatic brain injury

Implications for cellular therapy

Matthew T. Harting, Fernando Jimenez, Sasha D. Adams, David W Mercer, Charles S. Cox

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Background: Although cellular therapy has shown promise in the management of traumatic brain injury (TBI), microenvironment interactions between the intracerebral milieu and therapeutic stem cells are poorly understood. We sought to characterize the acute, regional inflammatory response after TBI. Methods: Rats underwent a controlled cortical impact (CCI) injury or sham injury, were killed at 6, 12, 24, 48, and 72 hours, and intracerebral fluid (IF) was isolated from the direct injury, penumbral, ipsilateral frontal, and contralateral regions. Cortical and hippocampal areas were also isolated. Regional cytokine levels were measured. Polymorphonuclear cell (PMN) oxidative burst and marker expression were assessed after incubation with the IF. Immunohistochemistry was used to identify intracerebral CD68+ cells (microglia/macrophages). Results: The proinflammatory cytokines interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosis factor-α were significantly elevated after CCI in the injury and penumbral regions. Increases in the same cytokines were localized to the cortex and the hippocampus. Increased PMN expression of CD11b and L-selectin was identified after incubation with injury or penumbral area IF, without change in PMN oxidative burst. CD68+ cells were noted in the direct injury and penumbral areas. Conclusion: The local cerebral milieu in the first 48 hours after TBI is highly proinflammatory. This response is most pronounced in areas at or proximal to the direct injury. The local, acute proinflammatory response after TBI may serve as a therapeutic target of early cell therapy or, conversely, may create an unfavorable local milieu, limiting the efficacy of early cellular therapy.

Original languageEnglish (US)
Pages (from-to)803-813
Number of pages11
JournalSurgery
Volume144
Issue number5
DOIs
StatePublished - Nov 1 2008

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Wounds and Injuries
Respiratory Burst
Cytokines
Secondary Prevention
Interleukin-1
Therapeutics
L-Selectin
Microglia
Cell- and Tissue-Based Therapy
Traumatic Brain Injury
Interleukin-6
Hippocampus
Stem Cells
Tumor Necrosis Factor-alpha
Immunohistochemistry
Macrophages

ASJC Scopus subject areas

  • Surgery

Cite this

Acute, regional inflammatory response after traumatic brain injury : Implications for cellular therapy. / Harting, Matthew T.; Jimenez, Fernando; Adams, Sasha D.; Mercer, David W; Cox, Charles S.

In: Surgery, Vol. 144, No. 5, 01.11.2008, p. 803-813.

Research output: Contribution to journalArticle

Harting, Matthew T. ; Jimenez, Fernando ; Adams, Sasha D. ; Mercer, David W ; Cox, Charles S. / Acute, regional inflammatory response after traumatic brain injury : Implications for cellular therapy. In: Surgery. 2008 ; Vol. 144, No. 5. pp. 803-813.
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AB - Background: Although cellular therapy has shown promise in the management of traumatic brain injury (TBI), microenvironment interactions between the intracerebral milieu and therapeutic stem cells are poorly understood. We sought to characterize the acute, regional inflammatory response after TBI. Methods: Rats underwent a controlled cortical impact (CCI) injury or sham injury, were killed at 6, 12, 24, 48, and 72 hours, and intracerebral fluid (IF) was isolated from the direct injury, penumbral, ipsilateral frontal, and contralateral regions. Cortical and hippocampal areas were also isolated. Regional cytokine levels were measured. Polymorphonuclear cell (PMN) oxidative burst and marker expression were assessed after incubation with the IF. Immunohistochemistry was used to identify intracerebral CD68+ cells (microglia/macrophages). Results: The proinflammatory cytokines interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosis factor-α were significantly elevated after CCI in the injury and penumbral regions. Increases in the same cytokines were localized to the cortex and the hippocampus. Increased PMN expression of CD11b and L-selectin was identified after incubation with injury or penumbral area IF, without change in PMN oxidative burst. CD68+ cells were noted in the direct injury and penumbral areas. Conclusion: The local cerebral milieu in the first 48 hours after TBI is highly proinflammatory. This response is most pronounced in areas at or proximal to the direct injury. The local, acute proinflammatory response after TBI may serve as a therapeutic target of early cell therapy or, conversely, may create an unfavorable local milieu, limiting the efficacy of early cellular therapy.

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