Leukocytes, macrophages and secondary brain damage following cerebral ischemia.
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.