Detecting activity-evoked pH changes in human brain

Department of Radiology, University of Iowa, Iowa City, IA 52242, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 05/2012; 109(21):8270-3. DOI: 10.1073/pnas.1205902109
Source: PubMed


Localized pH changes have been suggested to occur in the brain during normal function. However, the existence of such pH changes has also been questioned. Lack of methods for noninvasively measuring pH with high spatial and temporal resolution has limited insight into this issue. Here we report that a magnetic resonance imaging (MRI) strategy, T(1) relaxation in the rotating frame (T(1)ρ), is sufficiently sensitive to detect widespread pH changes in the mouse and human brain evoked by systemically manipulating carbon dioxide or bicarbonate. Moreover, T(1)ρ detected a localized acidosis in the human visual cortex induced by a flashing checkerboard. Lactate measurements and pH-sensitive (31)P spectroscopy at the same site also identified a localized acidosis. Consistent with the established role for pH in blood flow recruitment, T(1)ρ correlated with blood oxygenation level-dependent contrast commonly used in functional MRI. However, T(1)ρ was not directly sensitive to blood oxygen content. These observations indicate that localized pH fluctuations occur in the human brain during normal function. Furthermore, they suggest a unique functional imaging strategy based on pH that is independent of traditional functional MRI contrast mechanisms.

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Available from: Brian Dlouhy, May 19, 2014
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    • "nactivation and voltage gating ) as the result of pore mutation and protonation further illustrates the gating role of the outer pore in CNG channels . Changes in pH o can arise in a variety of physio - logical and pathophysiological conditions , such as neuro - nal activity , ischaemia and inflammation ( Kellum et al . 2004 ; Isaev et al . 2008 ; Magnotta et al . 2012 ) . Low pH acts as a negative feedback mechanism that inhibits the CNGA1 channel in a state - dependent manner and may represent an unrecognized endogenous signal regulating CNG physiological functions in diverse tissues ."
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    • "However, the functional relevance of ASIC1a in synaptic transmission remains unclear (47,48). Wemmie et al. recently detected local pH changes during normal brain activity in mouse and human brains (9). This study directly supports the potential activation of ASICs during brain activity, although attempts to measure the ASIC-mediated currents during synaptic transmission in hippocampal neurons have not been successful (6,45). "
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