Neuronal vacuole formation in the rat posterior cingulate/retrosplenial cortex after treatment with the N-methyl-d-aspartate (NMDA) antagonist MK-801 (dizocilpine maleate)

Cytoplasmic vacuoles appear in neurons of the posterior cingulate/retrosplenial cortex (PC/RS) of rats after treatment with N-methyl-d-aspartate (NMDA) receptor antagonists. Prominent dilatation of mitochondria and endoplasmic reticulum has been described within 2 h; however, the ultrastructural features of vacuole formation are unknown. To investigate this, the present study examined the PC/RS cortex of male rats (age 60–70 days) at 15, 30, 45, 60, 90, and 120 min after subcutaneous treatment with 1 mg/kg of the noncompetitive NMDA antagonist MK-801 (dizocilpine maleate, 5-methyl-10, 11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine). Subtle mitochondrial dilatation was identified in a few neurons as early as 15 min postdose (MPD). By 30 MPD, dilatation was more pronounced in mitochondria and also involved the endoplasmic reticulum and perinuclear space. Ribosomal disaggregation and degranulation were also evident by 30 MPD. At all subsequent time points, dilatation of mitochondria and endoplasmic reticulum progressed in severity. Although the relative involvement of mitochondria and endoplasmic reticulum varied, glia were not involved. These ultrastructural data suggest that after treatment with MK-801, mitochondrial dilatation precedes involvement of endoplasmic reticulum in vacuolization of susceptible PC/RS cortical neurons. The early mitochondrial effects identified in this study suggest an initial metabolic insult that rapidly progresses to affect endoplasmic reticulum and ribosomes. This strengthens the relationship between the ability of certain NMDA antagonists to induce energy perturbations and neuronal vacuoles in the same region of the rat cerebral cortex.     

The “suffocation alarm” theory of panic attacks: A critical commentary

In 1993 Klein proposed a “false suffocation alarm” theory of panic attacks, claiming that many spontaneous panic attacks are due to a “suffocation monitor” in the brain erroneously signaling a lack of useful air, and triggering an evolved “suffocation alarm system”. He proposed that carbon dioxide acts as a panic stimulus because rising arterial CO₂ suggests suffocation may be imminent. The present paper provides a critical analysis of Klein's theory and concludes that there is neither empirical evidence nor compelling argument to support the assumptions or the proposed neurological mechanism of a “suffocation alarm”, true or false, or a CO₂ “suffocation monitor”. Data relevant to the role of breathing in the phenomenon of panic can be parsimoniously subsumed within the domain of dyspnea.     

In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain.

Metastasis (the spread of cancer from a primary tumor to secondary organs) is responsible for most cancer deaths. The ability to follow the fate of a population of tumor cells over time in an experimental animal would provide a powerful new way to monitor the metastatic process. Here we describe a magnetic resonance imaging (MRI) technique that permits the tracking of breast cancer cells in a mouse model of brain metastasis at the single-cell level. Cancer cells that were injected into the left ventricle of the mouse heart and then delivered to the brain were detectable on MR images. This allowed the visualization of the initial delivery and distribution of cells, as well as the growth of tumors from a subset of these cells within the whole intact brain volume. The ability to follow the metastatic process from the single-cell stage through metastatic growth, and to quantify and monitor the presence of solitary undivided cells will facilitate progress in understanding the mechanisms of brain metastasis and tumor dormancy, and the development of therapeutics to treat this disease.     

Screening for glaucoma: age and sex of referrals and confirmed cases in England and Wales

This paper is based on a prospective survey covering 275,600 sight tests by optometrists in England and Wales. It analyses the age and sex distribution of 1402 referrals for suspected glaucoma and 456 confirmed cases of the disease. The proportion of sight tests which led to a confirmed case increased with age, for both sexes, to a maximum at approximately 70 years, and then tended to decline. Cases of glaucoma in people aged 36-51 years accounted for about a tenth of the total, which is more than is generally recognized. Wider adoption of routine tonometry for middle aged people would help to ensure that these cases are detected at an early stage. Confirmed cases of glaucoma in which raised intraocular pressure had not been given as a reason for referral, i.e. probable low tension glaucomas, increased from 5% of patients < 51 years old to 13% of patients > 75 years old. Glaucoma was found to be much more common in men.