Dorsolateral Prefrontal Cortex Glutamate/Gamma-Aminobutyric Acid (GABA) Alterations in Clinical High Risk and First-Episode Schizophrenia: A Preliminary 7-T Magnetic Resonance Spectroscopy Imaging Study.

Converging lines of evidence suggest that an imbalance between excitation and inhibition is present in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia (SCZ). Gamma-aminobutyric-acid (GABA) and, to a lesser extent, glutamate (Glu) abnormalities were reported in the DLPFC of SCZ patients, especially on the right hemisphere, by post-mortem studies. However, in vivo evidence of GABA, Glu, and Glu/GABA DLPFC abnormalities, particularly on the right side and the early stages of illness, is limited.

Development of frontal GABA and glutamate supports excitation/inhibition balance from adolescence into adulthood.

Animal and human postmortem studies provide evidence for changes in gamma-aminobutyric acid (GABA) and glutamate in prefrontal cortex (PFC) during adolescence, suggesting shifts in excitation and inhibition balance consistent with critical period plasticity. However, how GABA and glutamate change through adolescence and how the balance of these inhibitory and excitatory neurotransmitters changes is not well understood in vivo in humans. High field (7 Tesla) Magnetic Resonance Spectroscopic Imaging was used to investigate age-related changes in the balance of GABA/creatine (Cr) and glutamate/Cr in multiple developmentally-relevant regions of frontal cortex in 144 10-30-year-olds.

A longitudinal investigation of GABA, glutamate, and glutamine across the insula during antipsychotic treatment of first-episode schizophrenia.

Individuals with first-episode schizophrenia (FES) typically present with acute psychotic symptoms. Though antipsychotic drugs are the mainstay for treatment, the neurobiology underlying successful treatment remains largely elusive. Recent evidence from functional connectivity studies highlights the insula as a key structure in the neural mechanism of response.

Reduced GABA/glutamate in the thalamus of individuals at clinical high risk for psychosis.

Youth at clinical high risk (CHR) are a unique population enriched for precursors of major psychiatric disorders, especially schizophrenia (SCZ). Recent neuroimaging findings point to abnormalities in the thalamus of patients with SCZ, including chronic and early course patients, as well as in CHR individuals relative to healthy comparison groups, thus suggesting that thalamic dysfunctions are present even before illness onset. Furthermore, modeling data indicate that alteration between excitatory and inhibitory control, as reflected by alteration in GABAergic and glutamatergic balance (i.

Fast 3D rosette spectroscopic imaging of neocortical abnormalities at 3 T: Assessment of spectral quality.

Purpose: To use a fast 3D rosette spectroscopic imaging acquisition to quantitatively evaluate how spectral quality influences detection of the endogenous variation of gray and white matter metabolite differences in controls, and demonstrate how rosette spectroscopic imaging can detect metabolic dysfunction in patients with neocortical abnormalities.

Methods: Data were acquired on a 3T MR scanner and 32-channel head coil, with rosette spectroscopic imaging covering a 4-cm slab of fronto-parietal-temporal lobes. The influence of acquisition parameters and filtering on spectral quality and sensitivity to tissue composition was assessed by LCModel analysis, the Cramer-Rao lower bound, and the standard errors from regression analyses.

Correlated sodium and potassium imbalances within the ischemic core in experimental stroke: a 23Na MRI and histochemical imaging study.

This study addresses the spatial relation between local Na(+) and K(+) imbalances in the ischemic core in a rat model of focal ischemic stroke. Quantitative [Na(+)] and [K(+)] brain maps were obtained by (23)Na MRI and histochemical K(+) staining, respectively, and calibrated by emission flame photometry of the micropunch brain samples. Stroke location was verified by diffusion MRI, by changes in tissue surface reflectivity and by immunohistochemistry with microtubule-associated protein 2 antibody.

K⁺ dynamics in ischemic rat brain in vivo by ⁸⁷Rb MRI at 7 T.

The aims of the present study were as follows: (i) to perform the first (87)Rb MRI in live rats with focal ischemic stroke; and (ii) to test the hypothesis that K(+) egress from the brain in this model is quantifiable in individual animals by high-field (7-T) K/Rb substitution MRI. Rats preloaded with dietary Rb(+) (resulting in Rb/(K + Rb) replacement ratios of 0.1-0.

Inhomogeneous sodium accumulation in the ischemic core in rat focal cerebral ischemia by 23Na MRI.

Purpose: To test the hypotheses that (i) the regional heterogeneity of brain sodium concentration ([Na(+)](br)) provides a parameter for ischemic progression not available from apparent diffusion coefficient (ADC) data, and (ii) [Na(+)](br) increases more in ischemic cortex than in the caudate putamen (CP) with its lesser collateral circulation after middle cerebral artery occlusion in the rat.

Materials And Methods: (23)Na twisted projection MRI was performed at 3 Tesla. [Na(+)](br) was independently determined by flame photometry.

MAP2 immunostaining in thick sections for early ischemic stroke infarct volume in non-human primate brain.

The delineation of early infarction in large gyrencephalic brain cannot be accomplished with triphenyl-tetrazolium chloride (TTC) due to its limitations in the early phase, nor can it be identified with microtubule-associated protein 2 (MAP2) immunohistochemistry, due to the fragility of large thin sections. We hypothesize that MAP2 immunostaining of thick brain sections can accurately identify early ischemia in the entire monkey brain. Using ischemic brains of one rat and three monkeys, a thick-section MAP2 immunostaining protocol was developed to outline the infarct region over the entire non-human primate brain.

Sodium mapping in focal cerebral ischemia in the rat by quantitative (23)Na MRI.

Purpose: To validate (23)Na twisted projection magnetic resonance imaging (MRI) as a quantitative technique to assess local brain sodium concentration ([Na(+)](br)) during rat focal ischemia every 5.3 minutes.

Materials And Methods: The MRI protocol included an ultrashort echo-time (0.

NMR study of general anesthetic interaction with nAChR beta2 subunit.

The molecular basis of anesthetic interaction with membrane proteins has been explored via determination of anesthetic effects on the structure and dynamics of the extended second transmembrane domain (TM2e) of the human neuronal nicotinic acetylcholine receptor (nAChR) beta(2) subunit in dodecylphosphocholine (DPC) micelles by (1)H and (15)N solution-state NMR. Both 1-chloro-1,2,2-trifluorocyclobutane (F3) and isoflurane, two volatile general anesthetics, induced nonuniform changes in chemical shifts among residues in TM2e. Saturation transfer difference NMR experiments further confirmed the direct anesthetic interaction with TM2e.

Monitoring of brain potassium with rubidium flame photometry and MRI.

An animal model was developed to monitor [K(+)] in the brain using partial K(+) replacement with Rb(+) and (87)Rb MRI. Fifty-one rats were given 0-80 mM of RbCl in the drinking water for up to 90 days. Focal cerebral ischemia was produced in 15 of the animals.

Differences between arterial occlusive and cortical photothrombosis stroke models with magnetic resonance imaging and microtubule-associated protein-2 immunoreactivity.

The differences between two models of cerebral ischemia [middle cerebral arterial transection (MCAT) and cortical photothrombosis (PT)] were explored with multiparametric MRI of apparent diffusion coefficient trace (ADCtr), cerebral blood flow (CBF) and T1. Microtubule-associated protein-2 (MAP2) immunoreactivity sections aligned with the MR images in the same coronal plane were used to map the infarct and to guide region-of-interest selection. In ischemic cortex, the larger T1 increase in PT versus MCAT (42+/-7% vs.

Stroke onset time using sodium MRI in rat focal cerebral ischemia.

Background And Purpose: Thrombolytic therapy with intravenous tPA must be administered within 3 hours after stroke onset. However, stroke onset time cannot be established in 20% to 45% of potential patients. We propose that the rate of increase of the brain concentration of sodium ([Na+]br) after stroke, monitored using sodium MRI in a rat model of cortical ischemia, is linear in each individual animal, can locate the ischemic region, and can be used to estimate onset time.

NMR structure and dynamics of the second transmembrane domain of the neuronal acetylcholine receptor beta 2 subunit.

Structure and backbone dynamics of a selectively [(15)N]Leu-labeled 28-residue segment of the extended second transmembrane domain (TM2e) of the human neuronal nicotinic acetylcholine receptor (nAChR) beta(2) subunit were studied by (1)H and (15)N solution-state NMR in dodecylphosphocholine micelles. The TM2e structure was determined on the basis of the nuclear Overhauser effects (NOEs) and the hydrogen bond restraints, which were inferred from the presence of H(alpha)(i)-H(N)(i+3), H(alpha)(i)-H(beta)(i+3), and H(alpha)(i)-H(N)(i+4) NOE connectivity and from the slow amide hydrogen exchange with D(2)O. The TM2e structure of the nAChR beta(2) subunit contains a helical region between T4 and K22.

NMR structure and backbone dynamics of the extended second transmembrane domain of the human neuronal glycine receptor alpha1 subunit.

The structure and backbone dynamics of an extended second transmembrane segment (TM2e) of the human neuronal glycine receptor alpha(1) subunit in sodium dodecyl sulfate micelles were studied by (1)H and (15)N solution-state NMR. The 28-amino acid segment contained the consensus TM2 domain plus part of the linker between the second and third transmembrane domains. The presence of a well-structured helical region of at least 13 amino acids long and an unstructured region near the linker was evident from the proton chemical shifts and the pattern of midrange nuclear Overhauser effects (NOE).

NMR studies of drug interaction with membranes and membrane-associated proteins.

This review focuses on the recent developments in the study of drug interactions with biological membranes and membrane-associated proteins using nuclear magnetic resonance (NMR) spectroscopy and other spectroscopic techniques. Emphasis is placed on a class of low-affinity neurological agents as exemplified by volatile general anesthetics and structurally related compounds. The technical aspects are reviewed of how to prepare membrane-mimetic systems and of NMR approaches that are either in current use or opening new prospects.

Late reversal of cerebral perfusion and water diffusion after transient focal ischemia in rats.

Region-specific cerebral blood flow (CBF) and the apparent diffusion coefficient (ADC) of tissue water in the rat brain were quantified by high-field magnetic resonance imaging at 9.4 T in the rat suture occlusion model. Cerebral blood flow and ADC were compared during the short- (4.

ADC characterization of region-specific response to cerebral perfusion deficit in rats by MRI at 9.4 T.

Region-specific cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) of water in the rat brain were quantified in vivo by high-field MRI (9.4 T) for 6-7 h after middle cerebral artery occlusion (MCAO). Upon occlusion, average CBF fell from about 1.

Aggregation of Fe(III)TPPS(4) on Biological Structures Is pH-Dependent, Suggesting Oxo-Bridging in the Aggregates.

Interaction of the Fe(III) derivative of tetra(4-sulfonatophenyl)porphyrin (TPPS(4)), and diamagnetic ZnTPPS(4) and metal-free TPPS(4), with the simplest models for membranes and protein reaction centers, aqueous (AM) and reversed (RM) ionic micelles, was studied by high-resolution (1)H NMR and proton magnetic relaxation measurements. AM were much more sensitive than RM to the bulky porphyrins, seemingly, because of the more restricted motion of surfactant chains in AM. TPPS(4) and its derivatives were incorporated into the AM of cationic cetyltrimethylammonium chloride (CTAC) or zwitterionic lysophosphatidylcholine (LPC) near the terminal part of their hydrocarbon chains, as evidenced by a strong upfield shift of the corresponding peaks.