The N-methyl-D-aspartate antagonist, MK-801, fails to protect against neuronal damage caused by transient, severe forebrain ischemia in adult rats

The neuroprotective effects of dizocilipine maleate (MK-801), a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor/channel, were tested in the 4-vessel occlusion rat model of forebrain ischemia. Adult Wistar rats, treated intraperitoneally with MK-801 or saline using several different treatment paradigms were subjected to 5 (n = 208) or 15 (n = 62) min of severe, transient forebrain ischemia. In saline-treated animals, 15 min of ischemia (n = 13) produced extensive and consistent loss of pyramidal neurons in the CA1 zone of hippocampus. The degree and distribution of cell loss were not reduced by single dose preischemic administration of MK-801 at 1 (n = 7), 2.5 (n = 4), or 5 mg/kg (n = 8). In other animals subjected to 15 min of forebrain ischemia, multiple doses of MK-801 (5, 2.5, and 2.5 mg/kg) given immediately and at approximately 8 and 20 hr after cerebral reperfusion (n = 5) did not alter CA1 injury compared to saline-treated controls (n = 5). Five minutes of forebrain ischemia in saline-treated animals, (n = 82) resulted in significantly fewer (p less than 0.001) dead CA1 pyramidal cells and a greater variance compared to animals subjected to 15 min of ischemia. Power analysis of the preliminary saline-treated animals subjected to 5 min of ischemia (n = 22) indicated that 60 animals per group were necessary to detect a 15% difference between MK-801 and vehicle-treated groups. Multidose treatment with MK-801 (1 mg/kg) given 1 hr prior to 5 min of ischemia (n = 60) and again at approximately 8 and 16 hr after recirculation failed to attenuate hippocampal injury.(ABSTRACT TRUNCATED AT 250 WORDS)     

Extracellular pH in the brain during ischemia: relationship to the severity of lactic acidosis

On the basis of data showing a bimodal distribution of values for extracellular pH (pHe), and a discontinuous delta PCO2/delta lactate relationship, Kraig et al. (1986) proposed that H+ is grossly compartmentalized between neurons and glia in the ischemic brain. We measured delta pHe during ischemia, varying ischemic lactate contents between 9 and 38 mmol kg-1. No bimodal distribution was found, but delta pHe varied linearly with lactate content. Because we have also failed to record a discontinuous delta PCO2/delta lactate relationship, we conclude that major compartmentation of H+ does not occur during ischemia.     

Pituitary abnormalities in eating disorders: further evidence from MRI studies

1. The frequent occurrence of hypothalamo-pituitary dysfunction in patients with eating disorders as well as prior reports that nutritional and endocrine status influence pituitary morphology, led us to hypothesize that pituitary size and shape may be altered in patients with eating disorders. 2. Magnetic resonance imaging (MRI) does not use ionizing radiation and is currently one of the most feasible modalities available to study the pituitary gland in vivo. Using MRI, we have previously reported in a preliminary study that female patients with eating disorders had significantly smaller pituitary glands than controls. In addition MRI excluded any pituitary mass lesions. 3. In this report, we confirm our previous MRI findings and provide further evidence of pituitary abnormalities in an expanded sample of eating disorder patients. Preliminary data on pituitary volume estimates from MRI scans are provided for a subset of patients and controls.     

Sensory axonopathy in hereditary distal spinal muscular atrophy

A girl of 14 year is presented with a distal spinal muscular atrophy (SMA) with autosomal recessive inheritance. The technical findings are in agreement with the diagnosis. Light microscopical examination of sural nerve biopsy, including teased fiber studies and morphometry, showed no abnormalities. Electron microscopical investigation however demonstrated axonal pathology. The question arises if distal SMA is a distal axonopathy mainly of motor nerves, but to some extent also of sensory nerves.     

Regulation of alcohol consumption by the renin-angiotensin system: a review of recent findings and a possible mechanism of action.

The renin-angiotensin system has traditionally been associated with the regulation of fluid and electrolyte balance. In this review we summarize the data which ascribes a completely new function to this system, i.e., the regulation of alcohol consumption. In addition, we suggest a possible mechanism for this effect based on the concept of a satiety or stop process. The approach taken was to examine the effect on alcohol intake of a wide variety of drug, genetic, dietary, surgical and neurosurgical manipulations, each of which has a range of biological effects characteristic of that manipulation, but all of which share the common property of altering activity in the renin-angiotensin system. The effect of these manipulations on alcohol intake was most parsimoniously explained by reference to their ability to raise or lower activity in the renin-angiotensin system. Any intervention which modulates activity in this system, either directly or indirectly, is likely to have consequences for alcohol consumption.     

Primary and secondary lymphomas of the brain: an MRI study

Three types of lymphoma of the central nervous system are known: primary non-Hodgkin's malignant lymphoma (NHML), secondary NHML and neurological lesions of Hodgkin's disease. NHML's are rare tumours, often associated with immunodeficiency and presenting predominantly as neuropsychological disorders. In this study 8 patients were explored by CT and MRI, with pathological confirmation. None of our patients had AIDS. The most typical neuroradiological image of this type of tumour is that of a large and intensely contrast-enhanced tumoral mass which is often multifocal and periventricular with infiltration of the subarachnoidal spaces and leptomeninges. Mass effect and perifocal oedema are less pronounced than expected with tumours of that size. NHML's may totally regress under corticosteroid therapy. This tumour of obscure aetiology must be recognized as it is now increasingly frequent.     

Dimensional measurement of seasonal variation in mood and behavior.

Recent epidemiologic studies have found that the behaviors that characterize seasonal affective disorder (SAD) show seasonal variation in 92%-95% of the general population, suggesting that seasonal variation in behavior and mood is a continuous, dimensional variable extending throughout the general population, defined at the upper extreme by SAD. Research into population seasonality will require a dimensional measure of seasonal variation in mood and behavior that produces a broad, finely graded distribution of seasonality scores sensitive to individual differences throughout the entire range of scores. Accordingly, the Inventory of Seasonal Variation (ISV) was developed as such a measure. This study demonstrated that the ISV has high internal structural validity and is highly sensitive to individual differences in seasonality across its entire range of scores in the normal population. This latter characteristic is not shared by other existing measures of seasonality. Initial external validity of the ISV was supported in that the mean of ISV scores of a SAD sample was found to lie at the 97th percentile of the normal population of scores. Analysis of ISV scores revealed that a winter pattern of seasonality was reported by over 95% of subjects, a pattern that was more pronounced in women than men, while a summer type of seasonality was reported by only 0.6% of the general population.