These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: The protective effect of cyclosporin A upon N-acetylaspartate and mitochondrial dysfunction following experimental diffuse traumatic brain injury.
    Author: Signoretti S, Marmarou A, Tavazzi B, Dunbar J, Amorini AM, Lazzarino G, Vagnozzi R.
    Journal: J Neurotrauma; 2004 Sep; 21(9):1154-67. PubMed ID: 15453986.
    Abstract:
    Pre- and post-injury Cyclosporin A (CsA) administration has shown neuroprotective properties by ameliorating mitochondrial damage. The aim of this study was to assess the effect of CsA upon N-acetylaspartate (NAA) reduction and ATP loss, two sensitive markers of mitochondrial dysfunction and bioenergetic impairment. Adult male Sprague-Dawley rats were exposed to impact acceleration traumatic brain injury (2 m/450 g) and randomized into the following experimental groups: intrathecal CsA/vehicle treated (n = 12), intravenous CsA/vehicle treated (n = 18) and sham (n = 12). Intrathecal treatment consisted of post-injury (30 min) cisternal bolus of CsA or Vehicle (0.15 mL, 10 mg/kg). Intravenous administration consisted of 30 min post-injury continuous 1 hour infusion of either 20 or 35 mg/kg CsA or Vehicle. Quantitative HPLC analysis of whole brain samples was performed 6 h post-injury for levels of NAA and ATP. Following intrathecal delivery CsA demonstrated significant neuroprotection blunting a 30% NAA reduction (p < 0.001) and restoring 26% of the ATP loss (p < 0.005). The 20 mg/kg intravenous dose failed to ameliorate the biochemical damages while the 35 mg/kg dosage showed 36% NAA recovery and 39% ATP restoration (p < 0.001). In conclusion, CsA is capable of restoring ATP and blunting NAA reduction. Intravenous infusion of 35 mg/kg appears to be the optimal therapeutic strategy in this model. These findings contribute to the notion that CsA achieves neuroprotection, preserving mitochondrial function, and provides a rationale for the assessment of CsA in the clinical setting where MR spectroscopy can monitor NAA and ATP in brain-injured patients.
    [Abstract] [Full Text] [Related] [New Search]