Suppression of microglia activation after hypoxia-ischemia results in age-dependent improvements in neurologic injury

Ulas Cikla; Vishal Chanana; Douglas B Kintner; Lucia Covert; Taylor Dewall; Alex Waldman; Paul Rowley; Pelin Cengiz; Peter Ferrazzano

doi:10.1016/j.jneuroim.2015.12.004

Suppression of microglia activation after hypoxia-ischemia results in age-dependent improvements in neurologic injury

J Neuroimmunol. 2016 Feb 15:291:18-27. doi: 10.1016/j.jneuroim.2015.12.004. Epub 2015 Dec 12.

Authors

Ulas Cikla¹, Vishal Chanana², Douglas B Kintner³, Lucia Covert⁴, Taylor Dewall⁵, Alex Waldman⁶, Paul Rowley⁷, Pelin Cengiz⁸, Peter Ferrazzano⁹

Affiliations

¹ Waisman Center, University of Wisconsin, Madison, WI 53705, USA. Electronic address: cikla@wisc.edu.
² Waisman Center, University of Wisconsin, Madison, WI 53705, USA. Electronic address: chanana@pediatrics.wisc.edu.
³ Waisman Center, University of Wisconsin, Madison, WI 53705, USA. Electronic address: dkintner@pediatrics.wisc.edu.
⁴ Waisman Center, University of Wisconsin, Madison, WI 53705, USA. Electronic address: lcovert@wisc.edu.
⁵ Waisman Center, University of Wisconsin, Madison, WI 53705, USA. Electronic address: tdewall@wisc.edu.
⁶ Waisman Center, University of Wisconsin, Madison, WI 53705, USA. Electronic address: awaldman@wisc.edu.
⁷ Waisman Center, University of Wisconsin, Madison, WI 53705, USA. Electronic address: prawley@wisc.edu.
⁸ Waisman Center, University of Wisconsin, Madison, WI 53705, USA; Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA. Electronic address: cengiz@pediatrics.wisc.edu.
⁹ Waisman Center, University of Wisconsin, Madison, WI 53705, USA; Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA. Electronic address: ferrazzano@pediatrics.wisc.edu.

Abstract

We previously found increased microglial proliferation and pro-inflammatory cytokine release in infant mice compared to juvenile mice after hypoxia-ischemia (HI). The aim of the current study was to assess for differences in the effect of microglial suppression on HI-induced brain injury in infant and juvenile mice. HI was induced in neonatal (P9) and juvenile (P30) mice and minocycline or vehicle was administered at 2h and 24h post-HI. P9 minocycline-treated mice demonstrated early but transient improvements in neurologic injury, while P30 minocycline-treated mice demonstrated sustained improvements in cerebral atrophy and Morris Water Maze performance at 60days post-HI.

Keywords: Cerebral atrophy; Microglia; Neonatal hypoxia–ischemia; Neuroinflammation.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Aging*
Animals
Animals, Newborn
Brain / pathology*
Brain Injuries / drug therapy
Brain Injuries / etiology*
Brain Injuries / pathology*
CD11b Antigen / metabolism
Disease Models, Animal
Flow Cytometry
Functional Laterality
Hypoxia-Ischemia, Brain / complications*
Hypoxia-Ischemia, Brain / pathology
Learning Disabilities / drug therapy
Learning Disabilities / etiology
Leukocyte Common Antigens / metabolism
Magnetic Resonance Imaging
Maze Learning
Mice
Microglia / drug effects
Microglia / metabolism*
Microglia / pathology
Minocycline / therapeutic use
Neurologic Examination
Statistics, Nonparametric
Time Factors

Substances

CD11b Antigen
Leukocyte Common Antigens
Minocycline

Abstract

Publication types

MeSH terms

Substances

Grants and funding