Altered Neurochemical Profile after Traumatic Brain Injury:¹H-MRS Biomarkers of Pathological Mechanisms

Abstract

Specific neurochemicals measured with proton magnetic resonance spectroscopy (1H-MRS) may serve as biomarkers of pathological mechanism in the brain. We used high field in vivo 1H-MRS to measure a detailed neurochemical profile after experimental traumatic brain injury (TBI) in rats. We characterized neurochemical changes in the contused cortex and the normal-appearing perilesional hippocampus over a time course from 1 hour to 2 weeks after injury. We found significant changes in 19 out of 20 neurochemicals in the cortex, and 9 out of 20 neurochemicals in the hippocampus. These changes provide evidence of altered cellular metabolic status after TBI, with specific compounds proposed to reflect edema, excitotoxicity, neuronal and glial integrity, mitochondrial status and bioenergetics, oxidative stress, inflammation, and cell membrane disruption. Our results support the utility of 1H-MRS for monitoring cellular mechanisms of TBI pathology in animal models, and the potential of this approach for preclinical evaluation of novel therapies.

Longitudinal and Prognostic Evaluation of Mild Traumatic Brain Injury: A 1H-Magnetic Resonance Spectroscopy Study

“…19,68 Similar evidence of Cho depression has been observed in human studies of alcoholism, [69][70][71] smoking, 71 combat-related PTSD, 72 stroke, 73 and depression. 74 Indeed, the reduction of Cho/Cre may be suggestive of an increase in Cre and/or a decrease in Cho in the same region.…”

Differences in Callosal and Forniceal Diffusion between Patients with and without Postconcussive Migraine

“…At a molecular level, there are similarities between the pathophysiologic changes after mTBI and those seen with atraumatic migraines, including abnormalities of cellular sodium/ potassium homeostasis and increases in cellular markers of hypoxia. 9 At a macroscopic level, abnormalities in cerebral blood flow and subcortical connectivity 2,10 after mTBI mirror changes seen in patients with nontraumatic migraine. Structurally, similar regions of gray matter volume loss have been found in the frontal regions in patients with both nontraumatic migraines and chronic PTM.…”

High-field proton magnetic resonance spectroscopy reveals metabolic effects of normal brain aging

“…In vivo proton magnetic resonance spectroscopy ( 1 H-MRS) allows noninvasive quantification of neurochemicals related to specific cellular mechanisms. These neurochemicals can serve as imaging biomarkers of cellular and molecular changes, both in the context of normal brain development and aging, and under pathologic conditions (Harris et al, 2012; Lee et al, 2012; Tkac et al, 2003). For example, N-acetylaspartate (NAA) is synthesized in neuronal mitochondria in an energy-dependent manner, so a decrease in NAA may indicate neuronal loss or metabolic dysfunction.…”