| pubmed-article:3301009 | pubmed:abstractText | Transient injuries to the central nervous system, whether due to trauma or ischemia, often produce long lasting metabolic derangements, lipid peroxidation, edema, and falls in blood flow at the lesion site. Because these post-injury responses are believed to be causes of secondary injury, much research effort has been devoted to developing therapies that prevent them. Recent studies suggest that excessive Ca entry into injured cells instigates these post-injury responses. A new theory is proposed to explain these post-injury responses. This theory posits that Ca ions entering dying cells activate phospholipases that break down membranes to release phosphates. The phosphates then bind and precipitate Ca ions, producing the profound and prolonged decreases in extracellular Ca activity that have been observed in traumatized spinal cords and ischemic brains. The phospholipase activity also facilitates release of lipid peroxides which enhance edema and reduce blood flow. Both of these in turn decrease Ca diffusion to the lesion site and slow the recovery of extracellular Ca activity, giving the tissue time to recover and avoiding the consequences of rapid restoration of extracellular Ca activity. The theory suggests that central nervous tissues evolved these Ca-activated responses as a general mechanism to protect neurons against excessive Ca entry. Brain and spinal cord tissues contain very high concentrations of phosphates, many times greater than is necessary to bind all the Ca ions in the tissues. This excessive Ca buffering capacity enables the tissue to sacrifice a small proportion of severely injured cells to reduce Ca entry into less severely injured neurons. This process will also rapidly eliminate moribund cells that may otherwise linger and consume oxygen and metabolic substrates better utilized by the remaining cells. If confirmed, this theory raises serious questions concerning the current experimental therapeutic approaches to CNS trauma and stroke. Therapy should perhaps be designed to optimize rather than to abort the post-injury responses. | lld:pubmed |
