Role of calcineurin in XXXX -mediated hypoxic injury to white matter.

@entity14855 @entity35 @entity870 @entity8119 @entity3446 @entity205 @entity519 @entity460 @entity1140 @entity141 @entity528 @entity130
BACKGROUND CONTEXT: @entity460 influx into cells is responsible for initiating the "final pathway" to cell death in neuronal tissue after traumatic or @entity130 . The specific pathways in this cascade are myriad and the importance each one plays is controversial. It is clear, though, that blocking individual pathways confers protection to these tissues. PURPOSE: In the present study we examined the role of @entity205 (CsA), @entity1140 and @entity3446 in modulating the effects of @entity141 influx through their interactions with immunophilins and specifically the end result of @entity14855 modulation. METHODS: Dorsal columns were isolated from the spinal cord of adult @entity35 and injured by exposure to @entity519 conditions for 60 minutes. The samples were monitored electrophysiologically in an in vitro recording chamber (maintained at 37 C degrees ) during injury, and the @entity8119 ( @entity8119 ) was monitored with glass microelectrodes. The dorsal column was exposed to @entity519 Ringers solution alone or with the different immunosuppressants and compared with baseline readings. Functional recovery of the dorsal column was then assessed by recovery of the @entity8119 . RESULTS: The mean @entity8119 decreased to about 20% of baseline control levels during @entity519 and returned 53.8+/-7.6% of baseline (p<.05) after reoxygenation. CsA, an immunosuppressant known to inhibit calcineurin, promoted a significantly greater recovery of @entity8119 amplitude to 76.8+/-5.2% and 72.1+/-13.2% of control (p<.05) after @entity130 and reoxygenation of dorsal column white matter when applied at concentrations of 1 microM and 10 microM, respectively. @entity1140 , which also inhibits calcineurin, was applied at a concentration of 0.1 microM, and promoted @entity8119 amplitude recovery to 82.6+/-5.0% of control after @entity130 and reoxygenation of dorsal column white matter. The addition of @entity3446 (1 microM), which binds to the same immunophilin as @entity1140 , to the @entity1140 (0.1 microM) solution during @entity130 showed recovery of @entity8119 amplitudes to only 56.9+/-6.7% of control. Electron microscopy revealed remarkable protection of axons and prevention of organelle disruption in segments treated with @entity870 and @entity1140 during @entity519 when compared with @entity519 controls. CONCLUSION: In conclusion, both CsA and @entity1140 confer in vitro protection to dorsal columns during @entity130 at physiological temperatures, and @entity3446 blocks the protective effect of @entity1140 . Thus, calcineurin may play an important role in the physiology of @entity528 .
