Disruption of cellular elements and water in neurotoxicity: studies using electron probe X-ray microanalysis.
Regulation of elements and water in nerve cells is a complex, multifaceted process which appears to be vulnerable to neurotoxic events. However, much of our knowledge concerning the potential role of elements in nerve cell injury is limited by the relatively gross level of corresponding analyses. If we are to confirm and understand the proposed role, more precise and detailed information is needed. As indicated in this commentary, research employing electron probe microanalysis and digital X-ray imaging has begun to provide this necessary information. Recent EPMA studies of nerve and glial cells in the peripheral and central nervous systems have shown that each cell type and their corresponding morphologic compartments exhibit unique distributions of elements and water. The use of microprobe analysis has allowed us to document precisely how elements and water redistribute in morphological compartments of damaged nerve cells. Accumulating evidence from EPMA studies suggests that, rather than being an epiphenomenon, intracellular changes in diffusible elements might mediate the functional and structural consequences of neurotoxic insult. It is also evident from this research that elements other than Ca might play a pertinent role in the injury response and that changes in intraneuronal elemental composition might develop according to a specific temporal pattern, e.g., transection-induced sequential alterations in axonal K, Na, Cl, and Ca. Therefore, rather than conducting end-point studies, longitudinal investigations are necessary to define the sequential pattern of elemental perturbation associated with a given neurotoxic event. Such research can also help identify the role of individual elements in the injury response. Future microprobe studies should be combined with measurements of ion levels (e.g., using fura-2 or ion selective electrodes) to provide a comprehensive and dynamic view of elemental deregulation. In addition, parallel biochemical studies should be performed to determine mechanisms of elemental disruption and possible biochemical and metabolic consequences of this disruption. Although evidence presented in this commentary suggests that each type of neurotoxic event produces a characteristic pattern of decompartmentalization, further work is necessary to confirm this possibility. Finally, based on a presumed involvement of elements in nerve injury, efforts are currently underway in several laboratories to develop appropriate pharmacological therapies for certain chemical- and trauma-induced neuropathological conditions (Dretchen et al., 1986; El-Fawal et al., 1989; Beattie et al., 1989).(ABSTRACT TRUNCATED AT 400 WORDS)
LoPachin
R M
RM
Department of Anesthesiology, Medical School, SUNY, Stony Brook 11794-8480.
Saubermann
A J
AJ
D000818:Animals; D004577:Electron Probe Microanalysis; D015386:Hazardous Substances / Q000633:toxicity*; D006706:Homeostasis / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects*; D009474:Neurons / Q000737:chemistry / Q000187:drug effects*; D051381:Rats; D014882:Water-Electrolyte Balance / Q000187:drug effects*
D015386:Hazardous Substances; D007473:Ion Channels