Neuroscience Letters 475 (2010) 150–155 Contents lists available at ScienceDirect Neuroscience Letters journal homepage: www.elsevier.com/locate/neulet Magnetic resonance spectroscopy of the brain under mild hypothermia indicates changes in neuroprotection-related metabolites Kannie W.Y. Chan a,b , April M. Chow a,b , Kevin C. Chan a,b , Jian Yang a,b,c , Ed X. Wu a,b,d,∗ a Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Pokfulam, Hong Kong SAR, China b Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong SAR, China c Medical Imaging Center of the First Affiliated Hospital, School of Medicine of Xi’an Jiaotong University, Xi’an, Shannxi Province, China d Department of Anatomy, The University of Hong Kong, Pokfulam, Hong Kong SAR, China article info Article history: Received 8 January 2010 Received in revised form 24 March 2010 Accepted 25 March 2010 Keywords: Magnetic resonance spectroscopy MRS MRI MR Brain Hypothermia Mild hypothermia Neuroprotection Temperature abstract Brain hypothermia has demonstrated pronounced neuroprotective effect in patients with cardiac arrest, ischemia and acute liver failure. However, its underlying neuroprotective mechanisms remain to be elu- cidated in order to improve therapeutic outcomes. Single voxel proton magnetic resonance spectroscopy ( 1 H-MRS) was performed using a 7 Tesla MRI scanner on normal Sprague–Dawley rats (N = 8) in the same voxel under normothermia (36.5 ◦ C) and 30 min mild hypothermia (33.5 ◦ C). Levels of various brain proton metabolites were compared. The level of lactate (Lac) and myo-inositol (mI) increased in the cor- tex during hypothermia. In the thalamus, taurine (Tau), a cryogen in brain, increased and choline (Cho) decreased. These metabolic alterations indicated the onset of a number of neuroprotective processes that include attenuation of energy metabolism, excitotoxic pathways, brain osmolytes and thermoregulation, thus protecting neuronal cells from damage. These experimental findings demonstrated that 1 H-MRS can be applied to investigate the changes of specific metabolites and corresponding neuroprotection mecha- nisms in vivo noninvasively, and ultimately improve our basic understanding of hypothermia and ability to optimize its therapeutic efficacy. © 2010 Elsevier Ireland Ltd. All rights reserved. Hypothermia confers a marked protection of the brain and heart from various insults, such as post-ischemic neurological injury and cardiac arrest, in both humans and animal models [3,18,24,39]. Mild hypothermia prevents hypoxic or ischemic damage, and has been applied for neuroprotection in stroke, ischemia [24,28], car- diac arrest [18] and hepatic encephalopathy (HE) [1]. It delays the onset of HE and prevents brain edema in acute liver failure [31]. It is a more effective intervention than osmotic diuretics for treat- ing refractory intracranial hypertension in severe traumatic brain injury (TBI) and various acute neurological diseases [34]. However, underlying neuroprotective mechanisms of hypothermia are not yet fully understood. Hypothermia has been found to affect a series of biological events, which range from the brain metabolism to immunoin- flammatory processes [38]. Its neuroprotection is multifaceted and further complicated in specific diseases. Mechanisms of hypother- mia include reduction of cerebral metabolism, cerebral blood flow and apoptosis, and prevention of excitotoxic damage by inhibit- ∗ Corresponding author at: Department of Electrical and Electronic Engineering, Anatomy and Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. Tel.: +852 2859 7096; fax: +852 2559 8738. E-mail address: ewu@eee.hku.hk (E.X. Wu). ing the release of excitatory amino acids or inactivation of their receptors [30]. Other protective mechanisms include reduction in gliosis that leads to neuronal preservation [23], and dampening of the immune response and post-injury inflammation by preventing the immune cell infiltrations [26]. Ex vivo NMR studies and analysis of body fluids showed changes in levels of metabolites, like lactate, myo-inositol, taurine and glutamate during hypothermia [29,47]. In particular, taurine is regarded as the endogenous cryogen, and has a specific taurinergic pathway for thermoregulation [12,14]. The study of the associated neuroprotection mechanisms clar- ifies the role of hypothermia in disease treatments, especially in TBI [15]. Mild (34–35 ◦ C) verse moderate hypothermia (32–34 ◦ C), local verse systemic hypothermia and the duration of cooling could result in different therapeutic outcomes [18,22]. Brain and rectal temperature could vary in a range of 0.1–2 ◦ C in patients [37]. Moreover, concentrations of metabolites (such as ammonia) or osmolytes could be different between the plasma and cere- bral spinal fluid [31]. Hence, measuring the rectal temperature or plasma contents is not sufficiently specific for assessing the physiol- ogy of the brain in response to hypothermia in clinical practice. New parameters or methods are needed to better monitor and adminis- ter hypothermia. In particular, the ability to examine the metabolic changes and evaluate the outcomes of hypothermia in vivo is critical to the success of hypothermic therapy. 0304-3940/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2010.03.066