Triggering Receptor Expressed on Myeloid Cells 2 Deficiency Alters Acute Macrophage Distribution and Improves Recovery after Traumatic Brain Injury

Maha Saber, Olga Kokiko-Cochran, Shweta S. Puntambekar, Justin D. Lathia, Bruce Lamb

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Traumatic brain injury (TBI) affects 1.7 million persons annually in the United States (Centers for Disease Control and Prevention). There is increasing evidence that persons exposed to TBI have increased risk of the development of multiple neurodegenerative conditions, including Alzheimer disease (AD). TBI triggers a strong neuroinflammatory response characterized by astrogliosis, activation of microglia, and infiltration of peripheral monocytes. Recent evidence suggests that alterations in innate immunity promote neurodegeneration. This includes genetic studies demonstrating that mutations in triggering receptor expressed on myeloid cells 2 (TREM2) is associated with a higher risk for not only AD but also multiple neurodegenerative diseases. To examine whether TREM2 deficiency affects pathological outcomes of TBI, Trem2 knockout (Trem2-/-) and C57BL/6J (B6) mice were given a lateral fluid percussion injury (FPI) and sacrificed at 3 and 120 days post-injury (DPI) to look at both acute and chronic consequences of TREM2 deficiency. Notably, at 3 DPI, B6 mice exposed to TBI exhibited increased expression of TREM2 in the brain. Further, Trem2-/- mice exposed to TBI exhibited enhanced macrophage activation near the lesion, but significantly less macrophage activation away from the lesion when compared with B6 mice exposed to TBI. In addition, at 120 DPI, Trem2-/- mice exposed to TBI demonstrated reduced hippocampal atrophy and rescue of TBI-induced behavioral changes when compared with B6 mice exposed to TBI. Taken together, this study suggests that TREM2 deficiency influences both acute and chronic responses to TBI, leading to an altered macrophage response at early time points, and improved pathological and functional outcomes at later time points.

Original languageEnglish (US)
Pages (from-to)423-435
Number of pages13
JournalJournal of Neurotrauma
Volume34
Issue number2
DOIs
StatePublished - Jan 15 2017

Fingerprint

Myeloid Cells
Macrophages
Macrophage Activation
Wounds and Injuries
Knockout Mice
Alzheimer Disease
Traumatic Brain Injury
Percussion
Microglia
Centers for Disease Control and Prevention (U.S.)
Innate Immunity
Neurodegenerative Diseases
Atrophy
Monocytes
Mutation

Keywords

  • behavior
  • immunohistochemistry
  • inflammation
  • neurodegenerative disorders
  • traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Triggering Receptor Expressed on Myeloid Cells 2 Deficiency Alters Acute Macrophage Distribution and Improves Recovery after Traumatic Brain Injury. / Saber, Maha; Kokiko-Cochran, Olga; Puntambekar, Shweta S.; Lathia, Justin D.; Lamb, Bruce.

In: Journal of Neurotrauma, Vol. 34, No. 2, 15.01.2017, p. 423-435.

Research output: Contribution to journalArticle

Saber, Maha ; Kokiko-Cochran, Olga ; Puntambekar, Shweta S. ; Lathia, Justin D. ; Lamb, Bruce. / Triggering Receptor Expressed on Myeloid Cells 2 Deficiency Alters Acute Macrophage Distribution and Improves Recovery after Traumatic Brain Injury. In: Journal of Neurotrauma. 2017 ; Vol. 34, No. 2. pp. 423-435.
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