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Leukocytes, macrophages and secondary brain damage following cerebral ischemia
1Department of Neurology, School of Medicine, Keio University, Tokyo, Japan.
Abstract:
The involvement of white blood cells in microvascular derangement as a cause of secondary brain damage following cerebral ischemia is reviewed. Relevant data from the literature are arranged in the chronological sequence of the microvascular derangement of the brain that occurs after cerebral arterial occlusion (as based on our own experimental observations). The inflammatory processes which appeared to be elicited by polymorphonuclear leukocytes (PMNL) in the ischemic region of the brain may begin with adhesion of PMNLs to endothelial cells, followed by blood-brain barrier disruption, transudation/exudation, edema, necrosis, and scar formation. Stimulated by cytokines released from damaged neurons and axons, two types of macrophages (ameboid and ramified) appear, increase in number in the ischemic lesion, and engulf the debris of dead neurons, degenerated axons. Further, macrophages may release cytokines which stimulate healing processes, such as astroglial proliferation and revascularization, and release neurotoxins which could gradually kill surviving neurons. Even under such circumstances, individual leukocytes/macrophages are well regulated by specific mediators/cytokines. An urgent task is thus to find ways of controlling these key mediators/cytokines to reduce the inflammatory process and the extent of neuronal death for attenuating the secondary brain damage, without altering their beneficial effects.
Insights
White blood cells, particularly polymorphonuclear leukocytes (PMNLs) and macrophages, drive secondary brain damage after ischemic stroke. Controlling inflammatory mediators is crucial to reduce neuronal death and brain injury.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Cerebral ischemia triggers microvascular derangement and secondary brain damage.
- White blood cells play a critical role in the inflammatory cascade following ischemic events.
Purpose of the Study:
- To review the involvement of white blood cells in secondary brain damage after cerebral ischemia.
- To chronologically arrange the sequence of microvascular derangement following cerebral arterial occlusion.
Main Methods:
- Literature review of inflammatory processes in ischemic brain regions.
- Analysis of experimental observations on cerebral arterial occlusion.
- Examination of leukocyte and macrophage roles in neuroinflammation.
Main Results:
- Polymorphonuclear leukocytes (PMNLs) initiate inflammation via endothelial adhesion, leading to blood-brain barrier disruption, edema, and necrosis.
- Macrophages clear debris but can also release neurotoxins, contributing to delayed neuronal death.
- Cytokines modulate inflammatory and healing processes, including astroglial proliferation and revascularization.
Conclusions:
- Inflammatory responses mediated by leukocytes and macrophages significantly contribute to secondary brain damage post-ischemia.
- Targeting key mediators and cytokines is essential to mitigate neuronal loss and brain injury while preserving beneficial functions.