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

• Published in: Neurological research (New York) 2008-06, Vol.30 (5), p.476-479
• Main Authors: Mirzayan, M. Javad, Klinge, Petra M., Ude, Sven, Hotop, Anke, Samii, Madjid, Brinker, Thomas, Korkmaz, Zekiye, Meyer, Geerd J., Knapp, Wolfram H., Samii, Amir
• Format: Article
• Language: English
• Subjects: Animals; Autoradiography; Brain - drug effects; Brain - metabolism; Brain - pathology; Brain Injuries - drug therapy; Brain Injuries - metabolism; Brain Injuries - pathology; BRAIN INJURY; Calcium - metabolism; Calcium Radioisotopes - metabolism; Cyclosporine - therapeutic use; Disease Models, Animal; Male; NEUROPROTECTION; Neuroprotective Agents - therapeutic use; RAT; Rats; Rats, Sprague-Dawley; SHOCK; TRAUMA
• ISSN: 0161-6412; 1743-1328
• DOI: 10.1179/174313208X276916

Objective: As a neuroprotective drug, cyclosporin A (CsA) has been subject of multiple experimental works in traumatic brain injury (TBI) research. It is well known that CsA inhibits calcium (Ca 2+ ) induced mitochondrial permeability transition (mPT). The aim of this study was to investigate the influence of CsA on the alteration of Ca 2+ homeostasis after experimental brain injury. Methods: Sprague-Dawley male rats (n=36) with a mean weight of 330 g (280-350 g) were general anesthetized with isofluran through gas mask. The anesthetized animals (n=24) were subjected to a controlled cortical impact (CCI) over the left parietotemporal cortex using round-tip impounder with a 5 mm diameter at a velocity of ∼ 3.7 m/s and a penetration depth of 2 mm. The sham group (n=12) underwent anesthesia and craniotomy without CCI. In the CCI groups, CsA (n=12) or vehicle (n=12) was administered 15 minutes post-injury with a subsequent i.p. injection after 24 hours. Thirty-three hours after injury or sham craniotomy, 45 calcium ( 45 Ca) suspended in physiologic saline solution was injected in the left femoral vein. Five hours after isotope administration, animals were killed and the brain was quickly removed and placed in powdered dry ice. Coronal plane sections (20 μm thick) taken every 400 μm from the frontal cortex through the occipital cortex, were exposed to cyclotron films for 14 days at - 18° C. Relative optical density was utilized to provide a relative measure of 45 Ca accumulation within seven different structures. Results: The difference of 45 Ca accumulation (measured by relative optical density) in the CsA group was greater by 30-70% in the following structures compared to vehicle treated traumatized animals: temporal cortex, CA1, anteromedial and posteromedial thalamus (p