Lauric Acid Alleviates Neuroinflammatory Responses by Activated Microglia: Involvement of the GPR40-Dependent Pathway.

In several neurodegenerative diseases such as Alzheimer's disease (AD), microglia are hyperactivated and release nitric oxide (NO) and proinflammatory cytokines, resulting its neuropathology. Mounting evidence indicates that dietary supplementation with coconut oil (CNO) reduces the cognitive deficits associated with AD; however, the precise mechanism(s) underlying the beneficial effect of CNO are unknown. In the present study, we examined the effects of lauric acid (LA), a major constituent of CNO, on microglia activated experimentally by lipopolysaccharide (LPS), using primary cultured rat microglia and the mouse microglial cell line, BV-2. LA attenuated LPS-stimulated NO production and the expression of inducible NO synthase protein without affecting cell viability. In addition, LA suppressed LPS-induced reactive oxygen species and proinflammatory cytokine production, as well as phosphorylation of p38-mitogen activated protein kinase and c-Jun N-terminal kinase. LA-induced suppression of NO production was partially but significantly reversed in the presence of GW1100, an antagonist of G protein-coupled receptor (GPR) 40, which is an LA receptor on the plasma membrane. LA also decreased LPS-induced phagocytosis, which was completely reversed by co-treatment with GW1100. Moreover, LA alleviated amyloid-ß-induced enhancement of phagocytosis. These results suggest that attenuation of microglial activation by LA may occur via the GPR40-dependent pathway. Such effects of LA may reduce glial activation and the subsequent neuronal damage in AD patients who consume CNO.

S-Equol, a Major Isoflavone from Soybean, Inhibits Nitric Oxide Production in Lipopolysaccharide-Stimulated Rat Astrocytes Partially via the GPR30-Mediated Pathway.

Cumulative evidence indicates that estrogen receptor (ER) agonists attenuate neuroinflammation. Equol, a major isoflavone from soybean, exhibits estrogen-like biological activity, but their effect on inflammatory response has not been well established. Here, we investigated the effect of S-equol on nitric oxide (NO) production, well-known inflammatory change in astrocytes stimulated by LPS. S-Equol attenuated LPS-induced NO production with a concomitant decrease in expression of inducible NO synthase (iNOS). S-Equol did not affect LPS-induced increase in intracellular ROS production. Intracellular ER blocker ICI 182.780 had no effect on S-equol-induced decrease in NO production. Addition of G-15, antagonist of G protein-coupled receptor 30 which is nongenomic ER and located on cell surface, partially recovered S-equol-induced attenuation of NO production. These findings suggest that attenuation of NO production by S-equol may mitigate LPS-induced neuroinflammation in astrocytes. S-Equol may exert a glioprotective effect, at least in part, via a nongenomic effect.

Pure Amorphagnosia without Tactile Object Agnosia.

A 54-year-old female showed amorphagnosia without ahylognosia and tactile agnosia 40 days after the onset of right cerebral infarction. Her basic somatosensory functions were normal. The appreciation of substance qualities (hylognosia) was preserved, but the patient's inability to recognize the size and shape (morphagnosia) was confined to 2- and 3-dimensional shapes (amorphagnosia) in the left hand. However, the patient's ability to recognize real daily objects was well preserved. Brain MRI after admission showed ischemic lesions confined to the right pre- and postcentral gyri and the medial frontal cortex on DWI and FLAIR images. An analysis of SPECT images revealed that the most decreased areas were localized to the pre- and postcentral gyri, superior and inferior parietal lobules, supramarginal gyrus, and angular gyrus. Considering the previous reported cases, the responsible lesion for the impaired perception of hylognosia and morphagnosia may not necessarily be confined to the right hemisphere. To date, 5 reports (6 cases) of tactile agnosia have been published; 4 cases presented with both ahylognosia and amorphagnosia, while 1 presented with only amorphagnosia, and another showed amorphagnosia and mild ahylognosia. Our case is the first to present with only amorphagnosia without tactile agnosia. The mechanism for the well-preserved recognition of real objects may depend on the preserved hylognosia. Of note, there have been no reports showing only ahylognosia without amorphagnosia. Further studies are necessary to clarify whether or not patients with preserved hylognosia or morphagnosia retain the ability to perceive real objects.

[A patient with prosopagnosia which developed after an infarction in the left occipital lobe in addition to an old infarction in the right occipital lobe].

A 66-year-old, right-handed male, was admitted to our hospital with difficulty in recognizing faces and colors. He had suffered a stroke in the right occipital region three years earlier that had induced left homonymous hemianopsia, but not prosopagnosia. A neurological examination revealed prosopagnosia, color agnosia, constructional apraxia, and topographical disorientation, but not either hemineglect or dressing apraxia. The patient was unable to distinguish faces of familiar persons such as his family and friends, as well as those of unfamiliar persons such as doctors and nurses. Brain MRI demonstrated an old infarction in the right medial occipital lobe and a new hemorrhagic infarction in the left medial occipital lobe, including the fusiform and lingual gyrus. It is unclear whether a purely right medial occipital lesion can be responsible for prosopagnosia, or whether bilateral medial occipital lesions are necessary for this occurrence. The current case indicated that bilateral medial occipital lesions play an important role in inducing porsopagnosia.

Age-related white matter hyperintensities attenuated by compression from a chronic subdural hematoma: possible contribution of brain interstitial fluid to the formation of leukoaraiosis.

The origin of patchy white matter hyperintensities commonly seen in the elderly on magnetic resonance (MR) images with long repetition time (TR) is still controversial. We describe MR findings in older patients in whom white matter hyperintensities were attenuated by compression of the cerebral hemisphere from a chronic subdural hematoma. These sequential MR findings substantiate the hypothesis that leukoaraiosis may arise when drainage of the bulk flow of brain interstitial fluid is disturbed.

[A case of extramedullary multiple myeloma manifested as an epidural mass in the cervical spinal cord].

A 76-year-old man who rapidly developed quadriparesis was admitted to our hospital. MRI showed an epidural mass extending from C4 to C6, displacing the spinal cord anteriorly. It showed isointensity on the T1-weighted imagines, hyperintensity on the T2-weighted images, and diffuse hyperintensity with gadolinium enhancement. Plain radiographs, CT and MRI showed no evidence of bone involvement. Serum immunoelectrophoresis disclosed M-components of IgA and lambda light chains. This is the first report that an epidural myeloma in the cervical spinal cord caused compression of the cord without evidence of bone involvement.