135 A significant protection against NAA and glutamate loss was demonstrated,

suggesting that NSAIDs can protect against the neuronal pathology in AD. Similarly, dopamine administration, which had been the first-line pharmacologic treatment for PD for many years, reversed the abnormal striatal neurochemical levels (glutamate, glutamine, and GABA) in a PD model Inhibitors,research,lifescience,medical to WT levels.125 In a SCA1 model, conditional expression of the transgene was utilized to establish the sensitivity of MRS biomarkers to disease reversal.136 Namely, doxycycline treatment to suppress transgene expression was shown to reverse the abnormal neurochemical concentrations towards control levels.136 Furthermore, the potential to monitor Inhibitors,research,lifescience,medical treatment effects in

individual mice by utilizing multiple neurochemical levels at once was demonstrated in this study. In addition to longitudinal studies with chronic treatments, MRS can be utilized to monitor acute effects of drugs by obtaining time courses of metabolite levels. For example, neurochemical changes, including Inhibitors,research,lifescience,medical transient ones, upon acute phencyclidine (PCP) administration were captured in the rat brain, suggesting that MRS can be used to assess the effects of potential antipsychotic drugs in vivo.137 Similarly, the effects of the antieplleptic drug vigabatrin on GABA levels were Investigated in rat models using MRS,138 and increases similar to those observed in the human brain139 were detected. Inhibitors,research,lifescience,medical Low Casein Kinase inhibitor gyromagnetic ratio nuclei High field capabilities in brain research apply particularly to methodologies based on low gyromagnetic ratio nuclei such as 17O and 23Na imaging, and 13C, and 31P spectroscopy. For lower gyromagnetic nuclei, SNR gains provided by high magnetic fields can be more Inhibitors,research,lifescience,medical dramatic than what can be obtained for1Hin large

biological samples such as the human brain. For example, the SNR for the 17O nucleus is elevated ~ 4 fold in conducting biological samples, including the rat brain, with magnetic field in going from 4.7 T to 9.4 T140 while relaxation rates do not change. The SNR gain is within experimental error of expected theoretical Adenosine maximum of 3.4141 for these low frequencies since sample noise does not dominate SNR at these frequencies even in conducting samples. The biological information content in MR studies conducted with such low gyromagnetic nuclei can be unique. For example, the ability to image and quantitatively measure CMRC)2 in the rat140,142-144 and cat145 was demonstrated and used to measure oxygen consumption changes associated with neuronal activity to obtain functional images using 17O MR (Figure 6).