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 [10.1089/neu.2004.21.1154].

The protective effect of Cyclosporin A upon N-acetylaspartate and mitochondrial dysfunction following experimental diffuse traumatic brain injury

TAVAZZI, BARBARA;VAGNOZZI, ROBERTO
2004

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 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.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/27 - Neurochirurgia
eng
Energetic metabolism; High-performance liquid chromatography; Magnetic resonance spectroscopy; Mitochondrial dysfunction; N-acetylaspartate; Traumatic brain injury
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 [10.1089/neu.2004.21.1154].
Signoretti, S; Marmarou, A; Tavazzi, B; Dunbar, J; Amorini, Am; Lazzarino, G; Vagnozzi, R
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/31447
Citazioni
  • ???jsp.display-item.citation.pmc??? 22
  • Scopus ND
  • ???jsp.display-item.citation.isi??? 58
social impact