Metabolic Changes in the Vicinity of Brain Contusions: A Proton Magnetic Resonance Spectroscopy and Histology Study

Abstract

Proton MR spectroscopy (1H-MRS) has been previously used to monitor metabolic changes in areas of diffuse brain injury. We studied metabolism in the close vicinity of experimental traumatic brain contusions and remote on the contralateral side from 1h to 28d post-injury. Changes of creatine and phosphocreatine (Cr&PCr), N-acetylaspartate (NAA), choline (Cho), inositol (Ino), taurine (Tau), glutamate (Glu), and lactate (Lac) were assessed and compared to neuronal, glial and inflammatory changes in histology. In the pericontusional zone Cr&PCr, NAA, and Glu decreased immediately after trauma by -35%, -60%, and -37%, respectively, related to primary cell disintegration and secondary perturbations as reflected in histology. These metabolites partially recovered at 7d (-15%, -37%, and -21% respectively), in parallel to indicators of repair in immunhistochemistry. Control levels were not regained at 28d, in correlation to a decrease of viable neurons. Cho and Ino, initially lowered by -26% and -31% respectively, increased at 7d by +74% and 31%, reflecting glial activation and proliferation. The signal including the lactate resonance increased by >1000% with a maximum at 7d, possibly related to energy failure, inflammation and glial activation. A partial contribution of lipids to this signal cannot be fully excluded. The contralateral side showed mild astroglial activation in histology, but no changes in 1H-MRS. The study demonstrates the feasibility of volume selective 1H-MRS using the LCModel (Linear Combination of Model in vitro spectra of metabolites solutions) to monitor metabolic changes close to focal traumatic lesions and suggests how metabolic alterations can be differentiated in cause.

MR spectroscopy: Predicting long‐term neuropsychological outcome following pediatric TBI

“…Studies using MRSI in children also showed NAA/Cre reductions early after injury (10) as well as decreased NAA/Cho ratios up to three years post injury (36). Animal models of TBI that demonstrated decreases of NAA, found associations with regions of diffuse axonal injury (37) and neuronal loss (38,39). Therefore, the association of reduced NAA with poor cognitive outcome provides further evidence that NAA functions as a marker for neuronal and axonal injury in the setting of TBI in humans.…”

“…In this study, patients were imaged on average 6 Ϯ 4 days following injury, with some as long as 16 days after injury. Animal models have shown that metabolites such as Cho and mI increase soon after injury (38) whereas, NAA associated with neuronal dysfunction may remain depressed for days to weeks depending on the severity of injury (41) and may be permanent if neuronal loss has occurred (39). The time course for metabolic changes following TBI is not well established in humans and may vary by age as well as injury severity.…”

Non‐invasive detection of hippocampal sclerosis: correlation between metabolite alterations detected by 1H‐MRS and neuropathology

“…Furthermore, diffuse astrogliosis correlated with a decline in tNAA concentration, probably reflecting diffuse neuronal tissue degeneration. As m-Ins concentrations can be attributed to increased astroglial GFAP expression, m-Ins is probably an astroglial marker (25)(26)(27). Alterations in m-Ins concentrations in patients with TLE have been described previously (28,29).…”

Dynamic changes in N -methyl- d -aspartate receptors after closed head injury in mice: Implications for treatment of neurological and cognitive deficits

“…Traumatic and ischemic brain injury triggers a large, transient increase in excitatory amino acid transmitter efflux in the brain of experimental animals and human subjects (2)(3)(4)(5)(6). Glutamate activation of the N-methyl-D-aspartate (NMDA) receptor (NMDAR), which is a ligand-gated ion (calcium and sodium) channel, results in channel opening and ion influx into the cell.…”

“…Microdialysis studies of extracellular glutamate in human TBI and stroke patients suggested that the increase in glutamate in humans is more sustained [6 h to several days (7,8)] than in rodents, where it only lasts minutes (2)(3)(4)(5)(6). This result may have contributed to a decision to administer NMDAR antagonists in clinical trials of head injury for several days rather than once after severe nonpenetrating injury.…”