Pharmacotherapy for traumatic brain injury: a review.
Traumatic brain injury in the United States is a serious health problem: it is a significant factor in approximately half of all trauma-related deaths, and, leads to persistent, long-term neurologic dysfunction in survivors. Physiological changes that accompany brain trauma such as cardiovascular alterations, hypercapnia, hypoxiaischemia, metabolic dysfunction, and alterations in the endogenous neurochemical systems are associated with poor clinical outcome. Using a variety of animal models, experimental studies have begun to elucidate these neurochemical disturbances that underlie the behavioral deficits and the pathologic outcome. Modification of the post-traumatic neurochemical milieu can promote functional recovery. While a number of currently available pharmaceutical compounds have been reported to be effective in various animal models of TBI, their utility in the clinical setting has been disappointing [119]. New hope has arisen for the treatment of TBI, based upon new research findings regarding the development of novel pharmacological therapies for brain trauma. Reduction of brain temperature can maintain relative tissue homeostasis by lowering metabolic activity. Hypothermia has been attempted in patients over the past 50 years and recent experimental evidence suggests that posttraumatic hypothermia can attenuate EAA release and free-radical production [120]. In animal models, hypothermic treatment has attenuated post-traumatic neurologic motor dysfunction [121,122], improved histopathologic damage [123,124], and reduced the extent of cytoskeletal damage [120]. In addition, the armamentarium of potentially neuroprotective compounds, which has increased rapidly in the recent years, provides promising pharmacological therapies for the treatment of TBI.
Raghupathi
R
R
Department of Neurosurgery, University of Pennsylvania, Philadelphia, USA.
McIntosh
T K
TK
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D018377:Neurotransmitter Agents / Q000378:metabolism
D016207:Cytokines; D005609:Free Radicals; D006133:Growth Substances; D018377:Neurotransmitter Agents; D016718:Arachidonic Acid