TY - JOUR TI - Pathology of cerebral ischaemia - mechanisms involved in neuronal damage AU - Özben Tomris JN - Jugoslovenska medicinska biohemija PY - 2003 VL - 22 IS - 2 SP - 85 EP - 92 PT- Article AB- The following features of the ischaemic and postischaemic brain are the focus of interest: Development of acidosis, edema formation, calcium overload glutamate excitotoxicity, free radical formation and nitric oxide overproduction. The brain is critically dependent on its blood flow for a continuous supply of oxygen and glucose. Energy depletion has fundamental importance in the genesis of subsequent injurious events. Loss of ATP rapidly leads to a massive calcium influx and release of calcium from intracellular compartments. Extracellular concentrations of glutamate are markedly elevated in ischaemic brain tissue. Intracellular Ca2+ overload during ischemia has several deleterious consequences including the formation of reactive oxygen species. Nitrogen monoxide (NO) is an important mediator of cellular and molecular events which impacts the pathophysiology of cerebral ischemia. An increase in intracellular Ca2+ activates the enzyme NO synthase which catalyzes the synthesis of NO. NO is produced in neurons glia cells and vascular endothelium in central nervous system. Depending on its origin, its effects are varied. NO is a mediator having both neurotoxic and neuromodulator effects. Neuronal NO is the neurotoxic agent mediating glutamate toxicity and increasing acute ischaemic damage. Vascular NO as a potent vasodilator and an inhibitor of platelet aggregation, may be beneficial in the early stages of focal cerebral ischemia. There is increasing evidence that ischaemic brain injury secondary to arterial occlusion is characterized by acute local inflammation, which involves accumulation of polymorphonuclear neutrophils. Overexpression of inflammatory mediators such as cytokines, chemokines and adhesion molecules promotes recruitment of leukocytes in the ischaemic area.