Artikel
Modified calcium accumulation after controlled cortical impact under Cyclosporin A treatment. A 45Ca autoradiographic study
Alteration des posttraumatischen Kalziumstoffwechsels unter Cyclosporin A im Rattenmodell ("Controlled Cortical Impact")
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Veröffentlicht: | 8. Mai 2006 |
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Objective: As a neuroprotective drug Cyclosporin A has been subject of multiple experimental studies in traumatic brain injury research. It is well known that Cyclosporin A inhibits Calcium induced mitochondrial permeability transition (mPT) and the subsequent release of proapoptotic proteins. We investigated the calcium homeostasis after CCI and Cyclosporin A treatment.
Methods: Sprague-Dawley male rats (n=36) with a mean weight of 330g (280-350 g) were anesthetized with Isofluran. The anesthetized animals (n=24) were subjected to a CCI over the left parieto-temporal cortex using round-tip impounder with a 5 mm diameter at a velocity of 3.7 m/sec and a penetration depth of 2 mm. Cyclosporin A (n=12) or vehicle (n=12) was administered 15 min post injury with a subsequent i.p. injection 24 h post-injury. One group of animals (n=12) underwent anesthesia and craniotomy without CCI. At 43 hours after injury 45Ca suspended in physiological saline solution was injected in the left femoral vein. Five hours after isotope administration animals were sacrified and the brain was quickly removed and placed in powdered dry ice. Coronal plane sections (20µm thick) taken every 400µm from the frontal cortex through the occipital cortex were exposed to Cyclotron films for 14 days. Relative optical density was utilized to provide a relative measure of 45Ca accumulation within seven different structures.
Results: The difference of calcium accumulation (measured by relative optical density) between the Cyclosporin A group and vehicle treated animals ranged between 30 and 70% in the following structures: caudate putamen, antero-medial thalamus, postero-medial thalamus, temporal cortex, occipital cortex, CA 1 and CA 3 (p<0.05). Only the frontal cortex showed no significant changes of the 45Ca accumulation between the different groups.
Conclusions: Posttraumatic calcium accumulation is modified under Cyclosporin A. There is a significant difference of calcium accumulation between the treatment groups.