Sequential proton MRS study of brain metabolite changes monitored during a complete pathological cycle of demyelination and remyelination in a lysophosphatidyl choline (LPC)-induced experimental demyelinating lesion model.

Metabolite changes in rat brain internal capsule (ic) area were monitored using volume localized in vivo proton MR spectroscopy (MRS) in a lysophosphatidyl choline (LPC)-induced experimental demyelinating lesion model of multiple sclerosis (MS), during the early phase (pre-acute) as well as during the complete pathological cycle of de- and re-myelination processes. The N-acetyl aspartate (NAA) peak showed reduction during the early phase of the lesion progression (demyelination) until day 10 and increased thereafter during remyelination. However, choline (Cho) and lipid resonances showed increased signal intensity during the early phase and decreased during remyelination. A progressive reduction of the NAA/Cr metabolite ratio in lesioned rats was observed during demyelination (up to day 10) compared with before lesion (control), and the value increased thereafter during remyelination (from day 15). During this period, however, the Cho/Cr ratio was a higher until day 10 and subsequently declined and was close to that calculated before lesion creation. The changes in NAA/Cr and Cho/Cr metabolite ratios correspond to changes in the individual metabolite peaks such as NAA and Cho. The increase in the intensity of the choline resonance during the early phase is indicative of the onset of an inflammatory demyelination process, and its rapid decrease thereafter is due to reduction in the inflammatory process associated with remyelination. Similarly, the increase in the intensity of lipids during the pre-acute stage of the lesion is attributed to active demyelination, which significantly decreased during remyelination. These MR results correlate well with the histology data obtained.

Changes in magnetic resonance imaging and sex behavior after 6-OHDA injection in the medial preoptic area.

Magnetic resonance imaging (MRI) of the brains of male rats was done before and after destroying the catecholamine (CA) fibers by local application of 6-hydroxydopamine (6-OHDA) in the medial preoptic area (mPOA). The male sexual behavior was also assessed before and after injection of this toxic drug. The administration of 6-OHDA (8 microg) resulted in highly variable lesions, as shown by MRI and confirmed by histological examination. A hyperintense area was visible either on one or on both sides, about 1-3 h after the administration of the drug. Postmortem histofluorescence showed destruction of CA fibers in the mPOA on those sides that showed hyperintense areas in the MRI. No CA fiber destruction was seen in those rats that had shown no change in MRI after 6-OHDA injection. There was a transient reduction in sex drive score in all the 6-OHDA-treated rats. The present findings point out a correlation between the MRI changes and CA fiber destruction, whereas the transient reduction in the sexual behavior was not related to these changes. It is suggested that some biochemical events related to 6-OHDA destruction of CA fibers may have been responsible for the hyperintensity seen in the MRI.

Role of medial preoptic area beta adrenoceptors in the regulation of sleep-wakefulness.

The role of the medial preoptic area (mPOA) beta adrenergic receptors in the regulation of sleep-wakefulness (S-W) was investigated in this study. S-W was assessed on the basis of polygraphic recording of EEG, EMG and EOG in free moving rats. Intracerebral microinjection of beta agonist, isoproterenol, into the mPOA produced arousal. The study was also conducted on another set of rats in which noradrenergic (NE) innervation to the mPOA was destroyed by injecting 6-hydroxydopamine into the ventral noradrenergic bundle, in the brain stem. Local application of isoproterenol, into the mPOA, in these animals, did not produce any significant change in S-W. Thus, the increase in awake period obtained on isoproterenol administration was the result of its action on the presynaptic NE terminals. Possible involvement of other responses in the isoproterenol induced increase in wakefulness, is discussed.