Direct Comparison of Microglial Dynamics and Inflammatory Profile in Photothrombotic and Arterial Occlusion Evoked Stroke

Neuroscience. 2017 Feb 20;343:483-494. doi: 10.1016/j.neuroscience.2016.12.012. Epub 2016 Dec 18.

Abstract

Many focal cerebral ischemia models utilize the middle cerebral artery occlusion (MCAO) evoked by coagulation to induce ischemic damage in the cortex and mimic the pathology observed in human patients. A second, increasingly popular model, the photothrombotic stroke, uses a laser beam to irradiate the MCA after administration of a photosensitizing dye. This widely used procedure is slowly replacing the MCAO model because of the easiness of the surgical protocol and the reproducibility of the damage. However, the photochemical reaction also results in wider microvascular injury. In this study, we have evaluated the impact of these two types of stroke in the cell survival and evolution of stroke, focusing on microglial cells, the first responders to cell injury. Two groups of heterozygote Cx3CR1-GFP reporter mice (to follow microglia) were subject to stroke injury either with coagulator-mediated occlusion or photothrombotic MCA damage. Microglial cells' dynamics of activation and phagocytosis together with astrocytic response and leukocyte infiltration were characterized at 1, 3 and 7days after damage. Photothrombotic stroke delayed microglial and astrocytic invasion of the ischemic core and accumulation of phagocytic microglia. It also elicited higher levels of inflammatory cytokines/chemokines and increased infiltration from the periphery. In addition, only the neurons in the MCAO stroke showed phenotype plasticity by downregulating the transcription factor NeuN. These data provide a better understanding of the exact temporal and spatial dynamics of the inflammatory response in these two animal models of stroke and identify more relevant targets for human therapy.

Keywords: astrocytes; inflammation; ischemia; microglia; photothrombosis; stroke.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Brain Ischemia / etiology
  • Brain Ischemia / immunology
  • Brain Ischemia / pathology
  • CX3C Chemokine Receptor 1 / genetics
  • CX3C Chemokine Receptor 1 / metabolism
  • DNA-Binding Proteins
  • Disease Models, Animal*
  • Disease Progression
  • Electric Stimulation
  • Female
  • Gliosis / etiology
  • Gliosis / immunology
  • Gliosis / pathology
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Lasers
  • Leukocytes / metabolism
  • Leukocytes / pathology
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microglia / metabolism*
  • Microglia / pathology
  • Nerve Tissue Proteins / metabolism
  • Neurons / immunology
  • Neurons / pathology
  • Nuclear Proteins / metabolism
  • Phagocytosis / physiology
  • Stroke / etiology*
  • Stroke / immunology*
  • Stroke / pathology
  • Time Factors

Substances

  • CX3C Chemokine Receptor 1
  • Cx3cr1 protein, mouse
  • DNA-Binding Proteins
  • Nerve Tissue Proteins
  • NeuN protein, mouse
  • Nuclear Proteins
  • Green Fluorescent Proteins