Glutamate Excitoxicity Is the Key Molecular Mechanism Which Is Influenced by Body Temperature during the Acute Phase of Brain Stroke

Abstract

Glutamate excitotoxicity, metabolic rate and inflammatory response have been associated to the deleterious effects of temperature during the acute phase of stroke. So far, the association of temperature with these mechanisms has been studied individually. However, the simultaneous study of the influence of temperature on these mechanisms is necessary to clarify their contributions to temperature-mediated ischemic damage. We used non-invasive Magnetic Resonance Spectroscopy to simultaneously measure temperature, glutamate excitotoxicity and metabolic rate in the brain in animal models of ischemia. The immune response to ischemia was measured through molecular serum markers in peripheral blood. We submitted groups of animals to different experimental conditions (hypothermia at 33°C, normothermia at 37°C and hyperthermia at 39°C), and combined these conditions with pharmacological modulation of glutamate levels in the brain through systemic injections of glutamate and oxaloacetate. We show that pharmacological modulation of glutamate levels can neutralize the deleterious effects of hyperthermia and the beneficial effects of hypothermia, however the analysis of the inflammatory response and metabolic rate, demonstrated that their effects on ischemic damage are less critical than glutamate excitotoxity. We conclude that glutamate excitotoxicity is the key molecular mechanism which is influenced by body temperature during the acute phase of brain stroke.

Phosphene perception is due to the ultra-weak photon emission produced in various parts of the visual system: glutamate in the focus

“…Vibrational transitions of various 1 O 2 pairs lead to UPE emission with spectral peaks at approximately 470-480, 510-530, 560-580, 630-640, and 670 nm (Nakano et al, 1976). Another peak is at 703 nm (Khan and Kasha, 1970) and approximately 1270 nm (Baker and Kanofsky, 1991 In addition, as mentioned, glutamate has a significant function in thermoregulation by means of the NMDA ionotropic receptors (Yoshimatsu et al, 1993;Paro et al, 2003), and there is a significant association between temperature and glutamate excitotoxicity (Campos et al, 2012). Thus, glutamate-related phosphene induction through UPE may also be a possible mechanism relating fever (high body temperature) and phosphenes (Cervetto et al, 2007).…”

“…L-glutamate has a significant role in thermoregulation through NMDA ionotropic receptors (Yoshimatsu et al, 1993;Paro et al, 2003). There is a tight association between temperature and glutamate excitotoxicity (Campos et al, 2012).…”

MRI and MR Spectroscopy Features of Heat Stroke: A Case Report

“…All these physiologic processes happen concomitantly, causing the common result of neuronal dysfunction. The central nervous system dysfunction results in delirium, convulsion or coma (1,2,4,8,9,16,20). Rhabdomyolysis and multiorgan failure are other serious complications of heat stroke (6).…”

“…It could be the result of high body temperature or heat related hypoxic ischemic injury (1). Glutamate excitotoxicity during cerebral ischemia happens when a large amount of glutamate is released from the brain tissue into the extracellular space (20). There are a few studies in the literature proposing the possible role of excitotoxic injury in heat stroke (3,18).…”

“…In pathologic terms, the role of transporters is impaired, which results in glutamate accumulation in the synaptic cleft and in turn excessive activation of postsynaptic glutamate receptors with next massive Ca 2+ influx. Impaired calcium homeostasis makes nitric oxide synthesis, mitochondrial dysfunction, free radical production and programmed cell death which result in progressive neurodegeneration (20,22,23).…”