Effects of radiation combined injury on hippocampal function are modulated in mice deficient in chemokine receptor 2 (CCR2)

Antiño R. Allen, Kirsten Elise Eilertson, Sourabh Sharma, Danielle Schneider, Jennifer Baure, Barrett Allen, Susanna Rosi, Jacob Raber, John R. Fike

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Chemokines and their receptors play a crucial role in normal brain function as well as in pathological conditions such as injury and disease-associated neuroinflammation. Chemokine receptor-2 (CCR2), which mediates the recruitment of infiltrating and resident microglia to sites of central nervous system (CNS) inflammation, is upregulated by ionizing irradiation and traumatic brain injury. Our objective was to determine if a deficiency in CCR2 and subsequent effects on brain microglia affect neurogenesis and cognitive function after radiation combined injury (RCI). CCR2 knock-out (-/-) and wild-type (WT) mice received 4 Gy of whole body 137Cs irradiation. Immediately after irradiation, unilateral traumatic brain injury was induced using a controlled cortical impact system. Forty-four days postirradiation, animals were tested for hippocampus-dependent cognitive performance in the Morris water-maze. After cognitive testing, animals were euthanized and their brains snap frozen for immunohistochemical assessment of neuroinflammation (activated microglia) and neurogenesis in the hippocampal dentate gyrus. All animals were able to locate the visible and hidden platform locations in the water maze; however, treatment effects were seen when spatial memory retention was assessed in the probe trials (no platform). In WT animals that received combined injury, a significant impairment in spatial memory retention was observed in the probe trial after the first day of hidden platform training (first probe trial). This impairment was associated with increased neurogenesis in the ipsilateral hemisphere of the dentate gyrus. In contrast, CCR2-/- mice, independent of insult showed significant memory retention in the first probe trial and there were no differences in the numbers of newly born neurons in the animals receiving irradiation, trauma or combined injury. Although the mechanisms involved are not clear, our data suggests that CCR2 deficiency can exert a protective effect preventing the impairment of cognitive function after combined injury.

Original languageEnglish (US)
Pages (from-to)78-88
Number of pages11
JournalRadiation research
Volume180
Issue number1
DOIs
StatePublished - Jul 1 2013

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Radiation Injuries
Chemokine Receptors
mice
animals
Neurogenesis
impairment
Microglia
radiation
brain damage
Wounds and Injuries
brain
irradiation
platforms
probes
Dentate Gyrus
Cognition
Brain
hippocampus
Parahippocampal Gyrus
central nervous system

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

Cite this

Allen, A. R., Eilertson, K. E., Sharma, S., Schneider, D., Baure, J., Allen, B., ... Fike, J. R. (2013). Effects of radiation combined injury on hippocampal function are modulated in mice deficient in chemokine receptor 2 (CCR2). Radiation research, 180(1), 78-88. https://doi.org/10.1667/RR3344.1
Allen, Antiño R. ; Eilertson, Kirsten Elise ; Sharma, Sourabh ; Schneider, Danielle ; Baure, Jennifer ; Allen, Barrett ; Rosi, Susanna ; Raber, Jacob ; Fike, John R. / Effects of radiation combined injury on hippocampal function are modulated in mice deficient in chemokine receptor 2 (CCR2). In: Radiation research. 2013 ; Vol. 180, No. 1. pp. 78-88.
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Allen, AR, Eilertson, KE, Sharma, S, Schneider, D, Baure, J, Allen, B, Rosi, S, Raber, J & Fike, JR 2013, 'Effects of radiation combined injury on hippocampal function are modulated in mice deficient in chemokine receptor 2 (CCR2)', Radiation research, vol. 180, no. 1, pp. 78-88. https://doi.org/10.1667/RR3344.1

Effects of radiation combined injury on hippocampal function are modulated in mice deficient in chemokine receptor 2 (CCR2). / Allen, Antiño R.; Eilertson, Kirsten Elise; Sharma, Sourabh; Schneider, Danielle; Baure, Jennifer; Allen, Barrett; Rosi, Susanna; Raber, Jacob; Fike, John R.

In: Radiation research, Vol. 180, No. 1, 01.07.2013, p. 78-88.

Research output: Contribution to journalArticle

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T1 - Effects of radiation combined injury on hippocampal function are modulated in mice deficient in chemokine receptor 2 (CCR2)

AU - Allen, Antiño R.

AU - Eilertson, Kirsten Elise

AU - Sharma, Sourabh

AU - Schneider, Danielle

AU - Baure, Jennifer

AU - Allen, Barrett

AU - Rosi, Susanna

AU - Raber, Jacob

AU - Fike, John R.

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