Modified calcium accumulation after controlled cortical impact under cyclosporin A treatment: a 45Ca autoradiographic study

摘要

Objective: As a neuroprotective drug, cyclosporin A (CsA) has been subject of multiplenexperimental works in traumatic brain injury (TBI) research. It is well known that CsA inhibitsncalcium (Ca2z) induced mitochondrial permeability transition (mPT). The aim of this study wasnto investigate the influence of CsA on the alteration of Ca2z homeostasis after experimental brainninjury.nMethods: Sprague–Dawley male rats (n536) with a mean weight of 330 g (280–350 g) werengeneral anesthetized with isofluran through gas mask. The anesthetized animals (n524) werensubjected to a controlled cortical impact (CCI) over the left parietotemporal cortex using roundtipnimpounder with a 5 mm diameter at a velocity ofy3.7 m/s and a penetration depth of 2 mm.nThe sham group (n512) underwent anesthesia and craniotomy without CCI. In the CCI groups,nCsA (n512) or vehicle (n512) was administered 15 minutes post-injury with a subsequent i.p.ninjection after 24 hours. Thirty-three hours after injury or sham craniotomy, 45calcium (45Ca)nsuspended in physiologic saline solution was injected in the left femoral vein. Five hours afternisotope administration, animals were killed and the brain was quickly removed and placed innpowdered dry ice. Coronal plane sections (20 mm thick) taken every 400 mm from the frontalncortex through the occipital cortex, were exposed to cyclotron films for 14 days at 218uC.nRelative optical density was utilized to provide a relative measure of 45Ca accumulation withinnseven different structures.nResults: The difference of 45Ca accumulation (measured by relative optical density) in the CsAngroup was greater by 30–70% in the following structures compared to vehicle treatedntraumatized animals: temporal cortex, CA1, anteromedial and posteromedial thalamusn(p,0.05).nConclusion: Post-traumatic 45Ca accumulation is modified under CsA. The crucial neuroprotectiveneffect of CsA might be unrelated to a reduction of post-traumatic Ca2z accumulation,nespecially with regard to the importance of Ca2z as an intracellular messenger governing a largennumber of cellular functions. [Neurol Res 2008; 30: 476–479]