Attenuation of the blood flow response to physostigmine in the rat cortex deafferented from the basal forebrain.

Previous functional investigations in rats failed to demonstrate that the classical cholinesterase inhibitor, physostigmine, can compensate for cortical cholinergic deficit induced by deafferentation from the nucleus basalis magnocellularis (NBM). As these studies were carried out shortly after NBM lesion (1-2 weeks), we sought to determine whether compensatory effects of physostigmine would appear at a longer postlesion time (3-5 weeks). Cerebral blood flow was used as a quantitative measure of brain function. At 3-5 weeks after unilateral NBM lesion, interhemispheric comparisons in resting conditions showed that the cortical cholinergic deficit was still present and that blood flow was lower in cortical areas on the lesion side, similarly to what was observed after 1-2 weeks, while basal blood flow in intact hemispheres remained unchanged. In contrast, under physostigmine, blood flow became significantly lower in deafferented cortical areas at 3-5 weeks postlesion time, whereas there were no significant interhemispheric differences in the short term. Comparisons with saline-infused rats showed reduced blood flow responses to physostigmine in forebrain regions, e.g. in the parietal cortex from 83% to 25% at 1-2 and 3-5 weeks postlesion, respectively. These changes cannot be ascribed to a global loss of reactivity, since responses in brainstem regions (medulla, cerebellum) remained unchanged statistically. The results demonstrate a reduced responsiveness to physostigmine at the longer postlesion time, and support the existence of a cholinosensitive mechanism antagonizing NBM influence. This mechanism may limit the activating effects of cholinergic agonists in the forebrain after NBM deafferentation.

Simultaneous two-voxel localized (1)H-observed (13)C-edited spectroscopy for in vivo MRS on rat brain at 9.4T: Application to the investigation of excitotoxic lesions.

(13)C spectroscopy combined with the injection of (13)C-labeled substrates is a powerful method for the study of brain metabolism in vivo. Since highly localized measurements are required in a heterogeneous organ such as the brain, it is of interest to augment the sensitivity of (13)C spectroscopy by proton acquisition. Furthermore, as focal cerebral lesions are often encountered in animal models of disorders in which the two brain hemispheres are compared, we wished to develop a bi-voxel localized sequence for the simultaneous bilateral investigation of rat brain metabolism, with no need for external additional references. Two sequences were developed at 9.4T: a bi-voxel (1)H-((13)C) STEAM-POCE (Proton Observed Carbon Edited) sequence and a bi-voxel (1)H-((13)C) PRESS-POCE adiabatically decoupled sequence with Hadamard encoding. Hadamard encoding allows both voxels to be recorded simultaneously, with the same acquisition time as that required for a single voxel. The method was validated in a biological investigation into the neuronal damage and the effect on the Tri Carboxylic Acid cycle in localized excitotoxic lesions. Following an excitotoxic quinolinate-induced localized lesion in the rat cortex and the infusion of U-(13)C glucose, two (1)H-((13)C) spectra of distinct (4x4x4mm(3)) voxels, one centred on the injured hemisphere and the other on the contralateral hemisphere, were recorded simultaneously. Two (1)H bi-voxel spectra were also recorded and showed a significant decrease in N-acetyl aspartate, and an accumulation of lactate in the ipsilateral hemisphere. The (1)H-((13)C) spectra could be recorded dynamically as a function of time, and showed a fall in the glutamate/glutamine ratio and the presence of a stable glutamine pool, with a permanent increase of lactate in the ipsilateral hemisphere. This bi-voxel (1)H-((13)C) method can be used to investigate simultaneously both brain hemispheres, and to perform dynamic studies. We report here the neuronal damage and the effect on the Tri Carboxylic Acid cycle in localized excitotoxic lesions.

The existence of biexponential signal decay in magnetic resonance diffusion-weighted imaging appears to be independent of compartmentalization.

It is generally believed that the apparent diffusion coefficient (ADC) changes measured by diffusion-weighted imaging (DWI) in brain pathologies are related to alterations in the water compartments. The aim of this study was to elucidate the role of compartmentalization in DWI via biexponential analysis of the signal decay due to diffusion. DWI experiments were performed on mouse brain over an extended range of b-values (up to 10,000 mm(-2) s) under intact, global ischemic, and cold-injury conditions. DWI was additionally applied to centrifuged human erythrocyte samples with a negligible extracellular space. Biexponential signal decay was found to occur in the cortex of the intact mouse brain. During global ischemia, in addition to a drop in the ADC in both components, a shift from the volume fraction of the rapidly diffusing component to the slowly diffusing one was observed. In cold injury, the biexponential signal decay was still present despite the electron-microscopically validated disintegration of the membranes. The biexponential function was also applicable for fitting of the data obtained on erythrocyte samples. The results suggest that compartmentalization is not an essential feature of biexponential decay in diffusion experiments.