PubMed · 3804424
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A K Verma, M C Maheshwari. 1986. Brain edema.. https://pubmed.ncbi.nlm.nih.gov/3804424/
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Heat stress (HS), a prevalent occupational and environmental hazard, has increasingly been recognized as a major contributor to multiple physiological disorders. The hypothalamus, a key regulator of thermoregulation and endocrine signaling, is especially susceptible to metabolic and inflammatory disturbances induced by HS. This study investigates the interplay among lipid metabolism, blood-brain barrier (BBB) integrity, and neuroinflammation in the hypothalamus under HS conditions, with a specific focus on apolipoprotein A1 (APOA1) as a potential protective factor. To achieve this, we integrated proteomic and lipidomic analyses with experimental validation in porcine and murine models. Proteomic analysis identified 266 differentially expressed proteins (DEPs) in the hypothalamus following HS, with significant enrichment in lipid metabolism pathways-especially glycerophospholipid (GP) metabolism-in which APOA1 displayed a marked increase. Lipidomic profiling further revealed HS-induced disruptions in phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CL) metabolism. Additionally, blood-brain barrier integrity was compromised, as evidenced by increased perivascular IgG extravasation, reduced pericyte coverage, and decreased expression of tight junction proteins ZO-1 and Occludin. HS also triggered pronounced neuroinflammation, characterized by elevated levels of iNOS, GFAP, and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6). Notably, administration of D-4F, an APOA1 mimetic peptide, alleviated blood-brain barrier damage, reduced neuroinflammation, and preserved synaptic integrity, thereby suggesting a neuroprotective role for APOA1 in HS-induced hypothalamic dysfunction. These findings underscore the critical role of lipid metabolism in maintaining hypothalamic homeostasis under HS conditions and position APOA1 as a key regulator with potential therapeutic implications for mitigating HS-related neuroinflammatory and metabolic disturbances.
The widely distributed software tools Cerius2 and ACD/log D Suite have been used to develop a new method for the prediction of the ratio of concentrations of a drug in the brain and blood (BB,quantified as log BB) from structure. The performances of all known blood-brain partitioning prediction methods are compared to give an up-to-date account on their accuracy, limitations, and usefulness. It is demonstrated that the new log BB prediction method is superior to other methods with regard to low-to-medium throughput log BB prediction, whereas the C2-ADME log BB two-dimensional (2D) method seems to offer the best compromise between speed and accuracy for ultra-high throughput processing of large compound databases for log BB prediction.
Continued studies in cognitive function in problem solving of graded difficulties has now proceeded through several thousand tests of high school students in a six-week period last summer (2000). The optical imager used 9 sources and 23 detectors operated in time multiplex to give an image of the prefrontal region in several seconds. Thus, the image can be acquired in the state prior to activation, during and following activation. The images are acquired at two wavelengths, 750 and 850 nm, from which the changes of blood concentration (blood pooling) and relative oxygenation/deoxygenation state (metabolic activity) can be obtained and with suitable calibrations converted into micromolar changes of total Hb concentration and fractional oxygenation, respectively. The imager has a wearable pad applied to the forehead and the electronics now presents the running average of the two quantities mentioned above in the 16 voxels which cover the prefrontal region in 1 sec. Thus the protocol involves a scanning through anagrams of graded difficulty which are known to include the range of maximal activation (>3 solutions in the 30 sec test interval or are too easy (>10), or too difficult. Anagrams are presented in a sequence of three, four, five, etc. letter anagrams to the maximal level of difficulty and then back down again to the starting point. Each anagram is displayed for approximately one minute. Computer scanning of the results gives histograms of the several hundred tests per individual in the "training" interval (for three weeks) and in the post training interval about 400 tests, each for 4 levels of difficulty (3 weeks). Usually two or three complete trials per day were achieved with the result that the group of 7 students produced over 2600 test results in 2000. The histogram displays are under study to determine: a) the most fruitful voxels, b) the fraction of the total tests that appeared in those voxels, and c) the maximum signal level observed in the histogram display in units of micromolar hemoglobin. The product of these two was taken as the Figure of Merit and their displays of the 16 voxels gave patterns for trained and untrained responses. The preliminary conclusions of this study were: a) that the training effect was very large, pretraining exhibited a chaotic voxel distribution for all difficulty levels while trained students gave a higher output and activated only one or two of the 16 voxels. If the tests were too easy, too hard, i.e., an ability/difficulty mismatch, frustration or disattention gave similar chaotic patterns (7); b) a match between difficulty and ability activated only a few voxels in similar locations. Since attention and success measures appear to be of interest in school room studies, a wearable imager with local LCD display can be supplied to the Senior class of the local high school for those individuals who have already had last Summer's training in anagrams. A wearable NIR measurement of metabolic activation and blood flow may be a useful educational aid. In summary, the optical method focuses attention on cognition activated oxygenation of prefrontal cortex.