ABSTRACT
Traumatic brain injury is the major cause of mortality and morbidity in the young age group.1 It induces acute transient edema and disruption of the blood-brain barrier, and persistent neurological deficits which include motor and memory impairments.2 The mechanisms underlying the production of these deficits are still unclear, and various mediators have been suggested to contribute to the secondary damage.3 The complex network of pathways that are triggered by the primary injury and are involved in both damage and recovery include the inflammatory response with the accumulation of cytokines and reactive oxygen species (ROS), excitatory amino acids, eicosanoids, hormones and neurotransmitters. All these mediators are triggered by the injury and have a role in its pathophysiology. In recent years, the concept of opposing responses of injury and healing has emerged, and the role of inflammatory mediators in both processes is emphasized.4-8 After the initiation of injury, various neurodestructive and neuroprotective genes are expressed. The neurodestructive mediators, such as the inflammatory cytokines and adhesion molecules, or enzymes like metalloproteases, phospholipases, inducible nitric oxide synthase (iNOS) and caspases, can drive brain inflammation to induce cell death either by necrosis or apoptosis. Neuroprotective genes include the neurotrophic and growth factors and anti-inflammatory cytokines that are either brain-derived or infiltrate from the blood. A balance between the antiand proinflammatory cytokines has been proposed as one of the key factors which controls the life and death of neurons.9 A shift of balance towards the death signals, e.g. by inhibition of survival signals,
may explain how a cytokine can exert both types of effect. The context of mediators and the interaction between the intracellular signals form the basis for the concept of the intracellular regulation which controls the dual role of cytokines in health and disease.10
