Contributions
Abstract: P936
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Experimental models
Metabolic alterations and acidosis are increasingly recognized as key players in neurodegeneration and neuroinflammation. Different MRI methods are available to characterize brain damage and MR-Spectroscopy (MRS) can also provide relevant biochemical information. In the present study, advanced MR methods were used to monitor both the metabolism and acidosis involvement in the experimental autoimmune encephalomyelitis (EAE) mouse and in a mouse model of focal cerebral ischemia induced by the middle cerebral artery occlusion (MCAO). Chronic EAE was induced in C57BL/6 mice (n=6) with the MOG35-55 peptide. MR Spectrums were acquired in the cerebellum and in striatum of EAE and MCAO mice, respectively. The extracellular pH was obtained in vivo by measuring the chemical shift of an exogenous probe (IEPA, Soirem Research SL) sensitive to acidosis. As expected, cerebellum and striatum have a distinct metabolic profile in healthy mice but pH values were similar (pH=7.3±0.1). At the acute phase of EAE, alanine and lactate levels tend to increase (+61.8% and +20.9%, respectively) while glucose slightly decreased (-12.3%), which could be related to mitochondrial dysfunction that contributes to axonal loss in MS. This modulation of the energy metabolism occurred in concomitance with a decrease of NAA levels (-22.7%) an index of neuronal dysfunction, as expected in both models. In addition, in EAE mice the glutathione was significantly increased (+19.2%) probably to overcome the oxidative stress due to inflammation and mitochondrial dysfunction. Interestingly, lactate that was highly increased in MCAO mice remained low although tissue acidification was clearly found (pH=6.9±0.3). Interestingly, this acidification was in concomitance with NAA decrease as found in MCAO mice. Our results clearly suggest that acidosis is associated with neuronal dysfunction but not with lactate increase, which supports the concept that this metabolite is not a hallmark of acidosis during neuroinflammation and neurodegeneration but is related to hypoxia. To conclude, both markers of neuronal functionality (NAA) and oxidative stress (glutathione) appear to be relevant index for early brain damage in EAE. A longitudinal study to follow the alterations of both metabolism and pH during EAE progression should help to further characterized disease process.
Disclosure: The authors declare no competing financial interests.
Abstract: P936
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Experimental models
Metabolic alterations and acidosis are increasingly recognized as key players in neurodegeneration and neuroinflammation. Different MRI methods are available to characterize brain damage and MR-Spectroscopy (MRS) can also provide relevant biochemical information. In the present study, advanced MR methods were used to monitor both the metabolism and acidosis involvement in the experimental autoimmune encephalomyelitis (EAE) mouse and in a mouse model of focal cerebral ischemia induced by the middle cerebral artery occlusion (MCAO). Chronic EAE was induced in C57BL/6 mice (n=6) with the MOG35-55 peptide. MR Spectrums were acquired in the cerebellum and in striatum of EAE and MCAO mice, respectively. The extracellular pH was obtained in vivo by measuring the chemical shift of an exogenous probe (IEPA, Soirem Research SL) sensitive to acidosis. As expected, cerebellum and striatum have a distinct metabolic profile in healthy mice but pH values were similar (pH=7.3±0.1). At the acute phase of EAE, alanine and lactate levels tend to increase (+61.8% and +20.9%, respectively) while glucose slightly decreased (-12.3%), which could be related to mitochondrial dysfunction that contributes to axonal loss in MS. This modulation of the energy metabolism occurred in concomitance with a decrease of NAA levels (-22.7%) an index of neuronal dysfunction, as expected in both models. In addition, in EAE mice the glutathione was significantly increased (+19.2%) probably to overcome the oxidative stress due to inflammation and mitochondrial dysfunction. Interestingly, lactate that was highly increased in MCAO mice remained low although tissue acidification was clearly found (pH=6.9±0.3). Interestingly, this acidification was in concomitance with NAA decrease as found in MCAO mice. Our results clearly suggest that acidosis is associated with neuronal dysfunction but not with lactate increase, which supports the concept that this metabolite is not a hallmark of acidosis during neuroinflammation and neurodegeneration but is related to hypoxia. To conclude, both markers of neuronal functionality (NAA) and oxidative stress (glutathione) appear to be relevant index for early brain damage in EAE. A longitudinal study to follow the alterations of both metabolism and pH during EAE progression should help to further characterized disease process.
Disclosure: The authors declare no competing financial interests.