Time Course of Early Metabolic Changes following Diffuse Traumatic Brain Injury in Rats as Detected by¹H NMR Spectroscopy

Abstract

Experimental models of traumatic brain injury (TBI) provide a useful tool for understanding the cerebral metabolic changes induced by this pathological condition. Here, we report on the time course of changes in cerebral metabolites after TBI and its correlation with early brain morphological changes using a combination of high-resolution proton magnetic resonance spectroscopy ((1)H MRS) and magnetic resonance imaging (MRI). Adult male Sprague-Dawley rats were subjected to closed head impact and examined by MRI at 1, 9, 24, 48, and and 72 h after the injury. Extracts from funnel frozen rat brains were then obtained and analyzed quantitatively by high-resolution (1)H MRS. Finally, statistical multivariate analysis was carried out to identify the combination of cerebral metabolites that best described the time evolution of diffuse TBI. The temporal changes observed in the concentration of cerebral metabolites followed three different patterns. The first pattern included taurine, threonine, and glycine, with concentrations peaking 24 h after the injury. The second pattern included glutamate, GABA, and alanine, with concentrations remaining elevated between 24 and 48 h post-injury. The third one involved creatine-phosphocreatine, N-acetylaspartate, and myo-inositol, with concentrations peaking 48 h after the injury. A multivariate stepwise discriminant analysis revealed that the combination of the organic osmolytes taurine and myo-inositol allowed optimal discrimination among the different time groups. Our findings suggest that the profile of some specific brain molecules that play a role as organic osmolytes can be used to follow-up the progression of the early diffuse brain edema response induced by TBI.

Severity of experimental traumatic brain injury modulates changes in concentrations of cerebral free amino acids

“…It has been indicated that both compounds, besides various still debated biological functions 51, 52, 53, 54, 55, play a determining contribution in controlling cerebral osmolarity 52, 55, 56. Even though some studies showed a decrease in Tau after TBI 57, 58, 59, our results are in line with those reported by others 60, 61 and are logically connected to dysfunctional NAA homeostasis following sTBI and to a precise role of osmolite regulator performed by cerebral Tau. It is also possible that the increase in Tau is finalized to counteract Glu excitotoxic effects since it has been reported that Tau can directly interact with the NMDA receptor subtype decreasing the binding of Glu 62.…”

SMIT2 mediates all myo-inositol uptake in apical membranes of rat small intestine

“…In response to an increase in osmolarity, intracellular MI concentration may rise up to 500-fold above its plasma concentration of ϳ30 M (9,11,12), where it prevents the accumulation effects of high ionic concentrations, which leads to DNA degradation (11a). This has been well documented in brain where conditions such as trauma (30), edema and hypernatremia (26,27,38) have been shown to increase MI levels. To reach such high intracellular concentrations, secondary active transport systems are required for MI.…”

Modelos experimentales de traumatismo craneoencefálico

“…Respecto a la hinchazón del cerebro o swelling cerebral, estudios recientes realizados en un modelo experimental puro de lesión difusa han puesto en evidencia la importancia de los osmolitos cerebrales en su desarrollo 86 . Los modelos experimentales que reproducen este tipo de daño incluyen los modelos por impacto-aceleración 20,73 (Tabla 1).…”