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A Cell Culture Model for Studying the Role of Neuron-Glia Interactions in Ischemia
Published on: November 14, 2020
Neuroprotective effect of exogenous microglia in global brain ischemia
Fumihiro Imai1, Hiromi Suzuki, Jumpei Oda
1Department of Neurosurgery, Fujita Health University, Toyoake, Aichi, Japan. fimai@fujita-hu.ac.jp
Abstract:
Exogenous microglia pass through the blood-brain barrier and migrate to ischemic hippocampal lesions when injected into the circulation. We investigated the effect of exogenous microglia on ischemic CA1 pyramidal neurons. Microglia were isolated from neonatal mixed brain cultures, labeled with the fluorescent dye PKH26, and injected into the subclavian artery of Mongolian gerbils subjected to ischemia reperfusion neuronal injury. PKH26-labeled microglia migrated to the ischemic hippocampal lesion, resulting in increased numbers of surviving neurons compared with control animals, even when injected 24 h after ischemia. Interferon-gamma stimulation of isolated microglia enhanced the neuroprotective effect. Administration of exogenous microglia resulted in normal performance in a passive avoidance-learning task. Additionally, administration of exogenous microglia increased the expression of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor in the ischemic hippocampus, and thus might have induced neurotrophin-dependent protective activity in damaged neurons. Peripherally injected microglia exhibited a specific affinity for ischemic brain lesions, and protected against ischemic neuronal injury in vivo. It is possible that administration of exogenous microglia can be developed as a potential candidate therapy for central nervous system repair after transitory global ischemia.
Insights
Administering exogenous microglia protects brain cells after ischemic injury. These cells migrate to damaged areas, improving neuron survival and cognitive function, offering a potential therapy for central nervous system repair.
Area of Science:
- Neuroscience
- Cell Biology
Background:
- Ischemic stroke causes neuronal injury in the brain.
- Microglia play a role in brain inflammation and repair.
- Therapeutic strategies for central nervous system repair are needed.
Purpose of the Study:
- To investigate the neuroprotective effects of exogenous microglia on ischemic brain injury.
- To determine if microglia can cross the blood-brain barrier and migrate to damaged areas.
- To assess the impact of exogenous microglia on neuronal survival and cognitive function.
Main Methods:
- Microglia were isolated, labeled with PKH26, and injected into the circulation of gerbils with ischemic injury.
- Migration of labeled microglia to the hippocampus was tracked.
- Neuronal survival, cognitive performance, and neurotrophin expression were evaluated.
Main Results:
- PKH26-labeled microglia successfully migrated to ischemic hippocampal lesions.
- Exogenous microglia administration increased the number of surviving neurons, even when given 24 hours post-ischemia.
- Interferon-gamma stimulation enhanced the neuroprotective effect.
- Microglia treatment improved performance in a passive avoidance-learning task and increased neurotrophin expression.
Conclusions:
- Peripherally administered microglia can cross the blood-brain barrier and target ischemic brain lesions.
- Exogenous microglia demonstrate neuroprotective effects in vivo, promoting neuronal survival and functional recovery.
- Exogenous microglia represent a potential therapeutic candidate for central nervous system repair after ischemic injury.
