Brain injury is the leading cause of death among individuals aged 28 to 45 years in the United States and Europe, with an incidence in the United States of 17 to 40 per 100,000 population. <sup>202 Rice D., MacKenzie E.   Cost of Injury in the United States San Francisco: Institute for Health and Aging, University of California (1989). 

Cliccare qui per andare alla sezione Riferimenti, 238 Sosin D.M., Sacks J.J., Smith S.M. Head injury-associated deaths in the United States from 1979 to 1986 JAMA 1989 ;  262 : 2251

Cliccare qui per andare alla sezione Riferimenti</sup> The occurrence of traumatic brain injury (TBI) requiring hospitalization is between 2000 and 5000 per 100,000 people, or between 2 and 12.5 million head injuries per year. <sup>129 Kraus J.F., McArthur D.L., Silberman T.A. Epidemiology of mild brain injury Semin Neurol 1994 ;  14 : 1

Cliccare qui per andare alla sezione Riferimenti</sup> The estimated cost of these injuries ranges from $1 billion to $25 billion per year. <sup>129 Kraus J.F., McArthur D.L., Silberman T.A. Epidemiology of mild brain injury Semin Neurol 1994 ;  14 : 1

Cliccare qui per andare alla sezione Riferimenti, 192 Pope A.M., Tailor A.R.   Disability in America: Toward a Nation Agenda for Prevention Washington, DC: National Academic Press (1991). 

Cliccare qui per andare alla sezione Riferimenti</sup> The cost to families and society is particularly high when it is considered that trauma to the central nervous system (CNS) is particularly common in young people.

Traumatic injury to the CNS results in neurologic dysfunction through both direct (immediate mechanical disruption of brain tissue and neural circuitry) and indirect (secondary or delayed) mechanisms. <sup>153 McIntosh T.K. The neurochemical sequelae of traumatic brain injury: Therapeutic implications Cerebrovasc Brain Metab Rev 1994 ;  6 : 109

Cliccare qui per andare alla sezione Riferimenti</sup> This delayed injury cascade develops over a period of hours to days to weeks following brain trauma. <sup>47 Cooper P.R.   Delayed brain injury: Secondary insults Bethesda, Maryland: National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health (1985). 

Cliccare qui per andare alla sezione Riferimenti, 228 Siesjö BK, Wieloch T: Brain injury: Neurochemical aspects. CNS Trauma Status Report, 1985, p 513.

Cliccare qui per andare alla sezione Riferimenti</sup> Although the precise mechanisms underlying post-traumatic secondary damage remain unclear, they are believed to result from alterations in neurochemical or cellular mediators initiated by the trauma. These cellular changes may include alterations in neurotransmitter release, neurotransmitter reuptake or clearance systems, changes in presynaptic or postsynaptic receptor binding, the synthesis of “autodestructive” and inflammatory mediators, or the alteration of endogenous neuroprotective or trophic factors. These fundamental changes in the neurochemistry of the CNS may exert deleterious effects on normal cerebral function including profound changes in regional cerebral blood flow (rCBF), alterations in ion homeostasis and brain swelling, and alterations in the local metabolic environment. <sup>226 Siesjö B.K.   Brain Energy Metabolism New York: John Wiley (1978). 

Cliccare qui per andare alla sezione Riferimenti</sup> Pathologic neurochemical activation following brain trauma may also directly kill neurons or glial cells (neurotoxic effects). Experimental identification of these injury mechanisms and elucidation of the timing of the pathologic neurochemical cascade initiated following trauma may provide enhanced opportunities for treatment with neuroprotective strategies designed to modify the synthesis, release, physiologic activity, or expression of pathogenic factors involved in these neurochemical cascades. Recently, new hope has arisen for the treatment of TBI, based on new research findings regarding the development of novel pharmacologic therapies for brain trauma. The experimental armamentarium of potentially neuroprotective pharmaceutical compounds has expanded enormously over the past several years. Many of these candidate compounds hold a great deal of promise, and this article reviews some of the more promising pharmacologic therapies for the resuscitation of the injured brain.