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            -acetyl-aspartate, total creatine, and myo-inositol in the epileptogenic human hippocampus

Petroff, Ognen A. C.; Errante, Laura D.; Kim, Jung Ho; Spencer, Dennis D.

doi:10.1212/01.wnl.0000068020.85450.8b

Cited by 62 publications

(61 citation statements)

References 46 publications

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“…Absolute quantification of tNAA concentrations revealed, however, that the reduction in the NAA/Cr ratio resulted from decreased tNAA concentrations while Cr concentrations remained unchanged. In addition to clinical in vivo examination, 1 H-MRS has been investigated in vitro (38) and using animal models (39). The study of Petroff et al (38) puts the above results into perspective.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to clinical in vivo examination, 1 H-MRS has been investigated in vitro (38) and using animal models (39). The study of Petroff et al (38) puts the above results into perspective. In vitro 1 H-MRS of hippocampal specimens at 11.75 T did not reveal a significant association between hippocampal neuron loss and cellular content of NAA, Cr or m-Ins.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2007

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ABSTRACT:We assessed 1 H-MRS as a screening tool for detection of hippocampal sclerosis in patients with temporal lobe epilepsy (TLE).1 H-MRS was carried out in the hippocampus of 23 patients with unilateral TLE. Metabolite alterations detected by 1 H-MRS correlated with degree of segmental neuronal cell loss and amount of astrogliosis. Positive correlation was found between total N-Acetylaspartate (tNAA) reduction and neuronal density in hippocampal CA1 (P < 0.001), CA3 (P ¼ 0.015), and CA4 subfields (P ¼ 0.031) and the dentate gyrus (P ¼ 0.006). Neuronal cell loss in CA1 turned out to be the most predictive and only significant variable for tNAA reduction (P ¼ 0.027). The association between myo-inositol (m-Ins) and astroglial glial fibrillary acidic protein (GFAP) expression revealed significantly increased m-Ins concentrations associated with diffuse astrogliosis (m-Ins ¼ 6.4 AE 1.1 institutional units) compared with gliosis restricted to isolated sectors of the hippocampus (i.e. hilus) (m-Ins ¼ 5.2 AE 1.2 institutional units) (P ¼ 0.039). A negative correlation was found between m-Ins and neuronal loss in the CA4 subfield of the hippocampus (P ¼ 0.028). Our results support 1 H-MRS as a suitable non-invasive method for preoperative identification of hippocampal sclerosis in patients with TLE. The extent of tNAA reduction correlates with hippocampal neuronal cell density. Furthermore, m-Ins is associated with the extent of hippocampal astrogliosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2007

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“…42 Thus, astrocytes in the sclerotic hippocampus seem to have a reduced capacity for glutamine synthesis and ammonia detoxification. Indeed, extracellular glutamine levels 43 and cellular glutamine levels 10,44 are reported reduced in the epileptogenic (sclerotic) hippocampus.…”

Section: Astrocytes Specific Enzymesmentioning

confidence: 99%

“…Analysis of the pathology and electrophysiology of 151 hippocampi removed in the Yale surgical series revealed that after surgery, 84% of patients with sclerotic hippocampi had an excellent (Engel class I) outcome. 9 In these sclerotic hippocampi, in addition to a greater than 50% loss of neurons, the glial density is increased by approximately 80% compared to nonsclerotic hippocampi and neurologically normal autopsy controls 10,11 (FIG. 1).…”

Section: Introductionmentioning

confidence: 99%

Astrocytes and Epilepsy

2010

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Summary: Astrocytes form a significant constituent of seizure foci in the human brain. For a long time it was believed that astrocytes play a significant role in the causation of seizures. With the increase in our understanding of the unique biology of these cells, their precise role in seizure foci is receiving renewed attention. This article reviews the information now available on the role of astrocytes in the hippocampal seizure focus in patients with temporal lobe epilepsy with hippocampal sclerosis. Our intent is to try to integrate the available data. Astrocytes at seizure foci seem to not be a homogeneous population of cells, and in addition to typical glial fibrillary acidic protein, positive reactive astrocytes also include a population of neuron glia-2-like cells The astrocytes in sclerotic hippocampi differ from those in nonsclerotic hippocampi in their membrane physiology, having elevated Naϩ channels and reduced inwardly rectifying potassium ion channels, and some having the capacity to generate action potentials. They also have reduced glutamine synthetase and increased glutamate dehydrogenase activity. The molecular interface between the astrocyte and microvasculature is also changed. The astrocytes are also associated with increased expression of many molecules normally concerned with immune and inflammatory functions. A speculative mechanism postulates that neuron glia-2-like cells may be involved in creating a high glutamate environment, whereas the function of more typical reactive astrocytes contribute to maintain high extracellular Kϩ levels; both factors contributing to the hyperexcitability of subicular neurons to generate epileptiform activity. The functions of the astrocyte vascular interface may be more critical to the processes involved in epileptogenesis.

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“…NAA is a metabolite produced within neuronal mitochondria that reflects neuronal density and functional viability. 21,22 Such biochemical-cognitive associations have not been explored in opiateusing populations. This finding and biochemical imaging technique (i.e.…”

Section: Introductionmentioning

confidence: 99%

A combined spectroscopic and functional MRI investigation of the dorsal anterior cingulate region in opiate addiction

et al. 2007

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Converging neuropsychological and functional neuroimaging evidence indicates that the dorsal anterior cingulate cortex (dACC) is dysfunctional in drug-addicted populations. Few studies, however, have investigated the biochemical and physiological properties of the dACC in such populations. We used proton magnetic resonance spectroscopy ( 1 H-MRS) together with functional magnetic resonance imaging (fMRI) to probe dACC biochemistry and physiological activity during performance of a behavioural control task in 24 opiate-dependent individuals (maintained on a stable dose of methadone or buprenorphine at the time of study) and 24 age, gender, intelligence and performance-matched healthy subjects. While both groups activated the dACC to comparable levels, the opiate-using group displayed relatively increased task-related activation of frontal, parietal and cerebellar regions, as well as reduced concentrations of dACC N-acetylaspartate and glutamate/glutamine. In addition, the opiateusing group failed to show the expected correlations between dACC activation and behavioural measures of cognitive control. These findings suggest that the dACC is biochemically and physiologically abnormal in long-term opiate-dependent individuals. Furthermore, opiate addicts required increased, perhaps compensatory, involvement of the fronto-parietal and cerebellar behavioural regulation network to achieve normal levels of task performance/behavioural control. These neurobiological findings may partly underpin key addiction-related phenomena, such as poor inhibitory control of drug-related behaviour in the face of adverse consequences, and may be of relevance to the design of future treatment studies.

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N -acetyl-aspartate, total creatine, and myo-inositol in the epileptogenic human hippocampus

Cited by 62 publications

References 46 publications

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

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

Astrocytes and Epilepsy

A combined spectroscopic and functional MRI investigation of the dorsal anterior cingulate region in opiate addiction

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N -acetyl-aspartate, total creatine, and myo-inositol in the epileptogenic human hippocampus

Cited by 62 publications

References 46 publications

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

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

Astrocytes and Epilepsy

A combined spectroscopic and functional MRI investigation of the dorsal anterior cingulate region in opiate addiction

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Product

Resources

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

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