Classical inflammation is a well-characterized secondary response to many acute disorders of the central nervous system. However, in recent years, the role of neurogenic inflammation in the pathogenesis of neurological diseases has gained increasing attention, with a particular focus on its effects on modulation of the blood-brain barrier BBB. The neuropeptide substance P has been shown to increase blood-brain barrier permeability following acute injury to the brain and is associated with marked cerebral edema. Its release has also been shown to modulate classical inflammation. Accordingly, blocking substance P NK1 receptors may provide a novel alternative treatment to ameliorate the deleterious effects of neurogenic inflammation in the central nervous system. The purpose of this paper is to provide an overview of the role of substance P and neurogenic inflammation in acute injury to the central nervous system following traumatic brain injury, spinal cord injury, stroke, and meningitis. 1. Introduction Acute disorders of the central nervous system (CNS), including traumatic brain injury (TBI), spinal cord injury (SCI), stroke, and meningitis, account for a significant disease burden worldwide, with CNS injury being the leading cause of death after trauma [1]. These acute neurological conditions affect individuals of all ages and both sexes alike resulting in significant morbidity and mortality. Despite the prevalence of these conditions, current treatments remain limited and largely inadequate. New therapies are urgently required in order to reduce the death and disability associated with these conditions. One feature which is central to each of these conditions is disruption to the blood-brain barrier (BBB)/blood-spinal cord barrier (BSCB) and subsequent development of vasogenic edema. As such, targeting this aspect of the injury cascade is likely to produce beneficial outcomes in each of these conditions. Recent reports on the role of the neuropeptide substance P (SP) and neurogenic inflammation in BBB dysfunction and genesis of cerebral edema following acute brain injury suggest that this pathway provides a novel target for therapeutic intervention. The current paper will provide an overview of the BBB and vasogenic edema, followed by a discussion of the role of SP and neurogenic inflammation in CNS injury. 2. Blood-Brain Barrier/Blood-Spinal Cord Barrier The BBB is a highly selective barrier that serves to protect the fragile brain microenvironment. It is the interface between the blood and the brain, separating the brain parenchyma from the blood
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