Prolonged White Matter Inflammation After Cardiopulmonary Bypass and Circulatory Arrest in a Juvenile Porcine Model

Ludmila Korotcova; Sonali Kumar; Kota Agematsu; Paul D Morton; Richard A Jonas; Nobuyuki Ishibashi

doi:10.1016/j.athoracsur.2015.04.017

Prolonged White Matter Inflammation After Cardiopulmonary Bypass and Circulatory Arrest in a Juvenile Porcine Model

Ann Thorac Surg. 2015 Sep;100(3):1030-7. doi: 10.1016/j.athoracsur.2015.04.017. Epub 2015 Jul 27.

Authors

Ludmila Korotcova¹, Sonali Kumar², Kota Agematsu¹, Paul D Morton¹, Richard A Jonas³, Nobuyuki Ishibashi⁴

Affiliations

¹ Children's National Heart Institute, Children's National Medical Center, Washington, DC; Center for Neuroscience Research, Children's National Medical Center, Washington, DC.
² George Washington University School of Medicine and Health Science, Washington, DC.
³ Children's National Heart Institute, Children's National Medical Center, Washington, DC; Center for Neuroscience Research, Children's National Medical Center, Washington, DC; George Washington University School of Medicine and Health Science, Washington, DC.
⁴ Children's National Heart Institute, Children's National Medical Center, Washington, DC; Center for Neuroscience Research, Children's National Medical Center, Washington, DC; George Washington University School of Medicine and Health Science, Washington, DC. Electronic address: nishibas@childrensnational.org.

Abstract

Background: White matter (WM) injury is common after neonatal cardiopulmonary bypass (CPB). We have demonstrated that the inflammatory response to CPB is an important mechanism of WM injury. Microglia are brain-specific immune cells that respond to inflammation and can exacerbate injury. We hypothesized that microglia activation contributes to WM injury caused by CPB.

Methods: Juvenile piglets were randomly assigned to 1 of 3 CPB-induced brain insults (1, no-CPB; 2, full-flow CPB; 3, CPB and circulatory arrest). Neurobehavioral tests were performed. Animals were sacrificed 3 days or 4 weeks postoperatively. Microglia and proliferating cells were immunohistologically identified. Seven analyzed WM regions were further categorized into 3 fiber connections (1, commissural; 2, projection; 3, association fibers).

Results: Microglia numbers significantly increased on day 3 after CPB and circulatory arrest, but not after full-flow CPB. Fiber categories did not affect these changes. On post-CPB week 4, proliferating cell number, blood leukocyte number, interleukin (IL)-6 levels, and neurologic scores had normalized. However, both full-flow CPB and CPB and circulatory arrest displayed significant increases in the microglia number compared with control. Thus brain-specific inflammation after CPB persists despite no changes in systemic biomarkers. Microglia number was significantly different among fiber categories, being highest in association and lowest in commissural connections. Thus there was a WM fiber-dependent microglia reaction to CPB.

Conclusions: This study demonstrates prolonged microglia activation in WM after CPB. This brain-specific inflammatory response is systemically silent. It is connection fiber-dependent which may impact specific connectivity deficits observed after CPB. Controlling microglia activation after CPB is a potential therapeutic intervention to limit neurologic deficits after CPB.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Age Factors
Animals
Cardiopulmonary Bypass / adverse effects*
Circulatory Arrest, Deep Hypothermia Induced / adverse effects*
Disease Models, Animal
Encephalitis / etiology*
Female
Microglia / pathology
Random Allocation
Swine
Time Factors
White Matter*

Abstract

Publication types

MeSH terms

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