title: Rescuing neurons and glia: is inhibition of apoptosis useful?
abstract: Traumatic brain injury (TBI) represents a leading cause of death in western countries. Despite all research efforts we still lack any pharmacological agent that could effectively be utilized in the clinical treatment of TBI. Detailed unraveling of the pathobiological processes initiated by/operant in TBI is a prerequisite to the development of rational therapeutic interventions. In this review we provide a summary of those therapeutic interventions purported to inhibit the cell death (CD) cascades ignited in TBI. On noxious stimuli three major forms of CD, apoptosis, autophagia and necrosis may occur. Apoptosis can be induced either via the mitochondrial (intrinsic) or the receptor mediated (extrinsic) pathway; endoplasmic reticular stress is the third trigger of caspase-mediated apoptotic processes. Although, theoretically pan-caspase inhibition could be an efficient tool to limit apoptosis and thereby the extent of TBI, potential cross-talk between various avenues of CD suggests that more upstream events, particularly the preservation of the cellular energy homeostasis (cyclosporine-A, poly ADP ribose polymerase (PARP) inhibition, hypothermia treatment) may represent more efficient therapeutic targets hopefully also translated to the clinical care of the severely head injured.
authors.affiliation: Department of Neurosurgery, University Medical School, Pécs University, Pécs, Hungary, Rét u. 2. H-7624, Hungary.
authors.forename: E
authors.initials: E
authors.lastname: Kovesdi
authors.forename: E
authors.initials: E
authors.lastname: Czeiter
authors.forename: A
authors.initials: A
authors.lastname: Tamas
authors.forename: D
authors.initials: D
authors.lastname: Reglodi
authors.forename: D
authors.initials: D
authors.lastname: Szellar
authors.forename: J
authors.initials: J
authors.lastname: Pal
authors.forename: P
authors.initials: P
authors.lastname: Bukovics
authors.forename: T
authors.initials: T
authors.lastname: Doczi
authors.forename: A
authors.initials: A
authors.lastname: Buki
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001930:Brain Injuries / Q000628:therapy*; D006801:Humans; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology