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Exogenous microglia enter the brain and migrate into ischaemic hippocampal lesions
1Department of Neurosurgery, Fujita Health University, Toyoake, Aichi, Japan. fimai@fujita-hu.ac.jp
Abstract:
We compared migration of systemically injected microglia into normal brain vs. ischaemic brain using a model of ischaemic hippocampal lesion. Microglia were labeled by a fluorescent dye using our standard phagocytosis procedure of microscopic particles and then injected intra-arterially into Mongolian gerbils subjected to ischaemia reperfusion neuronal injury. Delayed death of pyramidal neurons was confirmed by conventional histological analysis and dUTP nick end labeling (TUNEL) method. Clusters of dye-tagged cells migrating into the hippocampal ischaemic lesions were confirmed histochemically to be microglia. Since peripherally injected microglia exhibit specific affinity for ischaemic brain lesions and does not exacerbate ischaemic neuronal injury in the present model, we suggest that microglia may have a potential to be used as a piggy-back ride to deliver therapeutic genes and/or drugs for CNS repair following transitory global ischaemic insult.
Insights
Systemically injected microglia migrate to ischemic brain lesions in gerbils. These microglia show potential for delivering therapeutics for central nervous system (CNS) repair after ischemic injury.
Area of Science:
- Neuroscience
- Immunology
- Regenerative Medicine
Background:
- Ischemic stroke causes neuronal injury and death.
- Microglia, immune cells of the brain, play roles in neuroinflammation and repair.
- Targeting therapies to damaged brain regions remains a challenge.
Purpose of the Study:
- To investigate the migration of systemically injected microglia into ischemic brain lesions.
- To assess the safety and potential therapeutic application of microglia in a model of ischemic neuronal injury.
Main Methods:
- Microglia were fluorescently labeled and injected intra-arterially into Mongolian gerbils with induced ischemic hippocampal lesions.
- Neuronal death was confirmed using histological analysis and the TUNEL method.
- Migration and identity of labeled cells in lesions were confirmed histochemically.
Main Results:
- Dye-tagged microglia successfully migrated into the hippocampal ischemic lesions.
- The presence of injected microglia did not exacerbate ischemic neuronal injury.
- Pyramidal neuron death was confirmed in the affected brain regions.
Conclusions:
- Peripherally administered microglia exhibit specific affinity for ischemic brain lesions.
- Microglia hold potential as a delivery vehicle for therapeutic genes or drugs for central nervous system repair following transient global ischemic insults.