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 1hour 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.
Signoretti S., M.A. (2004). The protective effect of Cyclosporin A upon N-acetylaspartate and mitochondrial dysfunction following experimental diffuse traumatic brain injury. JOURNAL OF NEUROTRAUMA, 21(9), 1154-1167.
|Tipologia:||Articolo su rivista|
|Citazione:||Signoretti S., M.A. (2004). The protective effect of Cyclosporin A upon N-acetylaspartate and mitochondrial dysfunction following experimental diffuse traumatic brain injury. JOURNAL OF NEUROTRAUMA, 21(9), 1154-1167.|
|Settore Scientifico Disciplinare:||Settore MED/27 - Neurochirurgia|
|Revisione (peer review):||Sì, ma tipo non specificato|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1089/neu.2004.21.1154|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2004|
|Titolo:||The protective effect of Cyclosporin A upon N-acetylaspartate and mitochondrial dysfunction following experimental diffuse traumatic brain injury|
|Autori:||Signoretti S., Marmarou A., Tavazzi B., Dunbar J., Amorini A.M., Lazzarino G., Vagnozzi R.|
|Appare nelle tipologie:||01 - Articolo su rivista|