Brain injury: New insights into neurotransmitter and receptor mechanisms

The studies reviewed here represent a continuing search for mechanisms which play a role in neurological disturbances resulting from brain injury. Focal cortical freezing lesions in rats were shown to cause a widespread decrease in local cerebral glucose utilization (LCGU) in cortical areas of the lesioned hemisphere and this was interpreted as reflecting a depression of cortical activity. Such an interpretation was supported by the finding that in lesioned brain reduction of cerebral metabolism by pentobarbital and isoflurane was limited by the metabolic depression that has already occurred as a result of injury and by the demonstration that the energy status and substrate (glucose) supply in the cortical areas in the injured brain have not been compromised at the time when LCGU was decreased. Both the serotonergic and the noradrenergic neurotransmitter systems were implicated in functional alterations associated with injury. Cortical serotonin (5-HT) metabolism was increased throughout the lesioned hemisphere and complete inhibition of 5-HT synthesis withp-chlorophenylalanine ameliorated the decrease in cortical LCGU, interpreted as reflecting cortical functional depression. Cortical norepinephrine metabolism was bilaterally increased in focally injured brain, while prazosin, a selective ₁-noradrenergic receptor blocker, normalized cortical LCGU in the lesioned hemisphere. Low-affinity in vivo binding of [¹²⁵I]HEAT, another selective ₁-receptor ligand, was specifically increased in cortical areas of the lesioned hemisphere at the time of the greatest depression in LCGU, suggesting that ₁-adrenoreceptors may be of functional importance in injured brain. The general conclusion from this series of studies on mechanisms underlying functional disturbances in injured brain is that both the serotonergic and the noradrenergic neurotransmitter systems are involved in the widespread cortical depression which develops with time as a consequence of a focal lesion. The data are compatible with the inhibitory effects of NE and 5-HT in the cortex and with the hypothesis that these two transmitter systems affect cortical information processing.     

Hydrogen peroxide metabolism as an index of water stress tolerance in jute

Two species of jute plants Corchorus capsularis L. (cv. JRC 212) and C. olitorius L. (cv. JRO 632) were subjected to water stress for 2 and 4 days by withholding water. The relative water content (RWC) decreased in both plants under water stress but to a greater extent in C. olitorius . The C. olitorius seedlings also showed greater membrane injury than C. capsularis seedlings under water stress as was evident from injury index data. Water stress increased glycolate oxidase (EC 1.1.3.1.) activity more in C. olitorius than in C. capsularis . The activity of superoxide dismutase (SOD, EC 1.15.1.1.) and catalase (EC 1.11.1.6.) decreased under water stress and their decrease was higher in C. olitorius than in C capsularis . The level of hydrogen peroxide and lipid peroxidation also increased in both plants under water stress and the increase was higher in C. olitorius than in C. capsularis seedlings. Under comparable external water stress, C. capsularis seedlings showed lower membrane damage, lower H₂O₂ accumulation and lower lipid peroxidation than C. olilorius which may be taken as indicative of higher water stress tolerance capacity of the former.     

Chilling injury in coleus as influenced by photosynthetically active radiation, temperature and abscisic acid pretreatment. I. Morphological and physiological responses

Abstract. Coleus blumei Benth. (PI No. 354190), a green-leafed cultivar, was exposed to 5°C for 48 or 72 h after pretreatment for 48 h at two levels of photosynthetically active radiation (PAR) (8 and 320 μmol s⁻¹ m⁻²), two temperatures (13 and 20°C), and two abscisic acid (ABA) levels (0 and 200 g m⁻³ of the racemic mixture). Plants given low PAR for only 48 h prior to chilling treatment (48 or 72 h at 5°C) showed increased protection against chilling injury while those given high PAR were severely injured. The former plants were darker green, contained greater concentrations of chlorophyll- a , chlorophyll- b , total chlorophyll and anthocyanin and generally had a lower abscission rate than the latter plants. There were no differences, however, in chlorophyll- a/b ratio among plants grown at the two PAR levels, two temperatures or two ABA concentrations. Temperature and ABA pretreatment and number of hours at 5°C had no significant effect on chilling injury as measured by leaf chlorosis, but generally had a significant effect on leaf abcission, especially at 3 and 7 d after returning the plants to the greenhouse. Enclosing intact plants or excised shoots in plastic bags to maintain 100% relative humidity during 72 h chilling treatment failed to provide protection against chilling injury. These findings indicate that the protective effects of low PAR applied prior to chilling treatment may be as important or more important than that applied during chilling. They also indicate the importance of making careful measurements of PAR levels when conducting studies on chilling injury.     

Differences in reactivity of confluent and nonconfluent cultures of human endothelial cells toward thrombin-stimulated platelets or heparinized salt solution

Summary This study examined whether nonconfluent endothelial cell cultures reacted differently than confluent ones toward thrombin-stimulated platelets or a heparinized salt solution. The adherence to the endothelial cell cultures of⁵¹Cr-labeled human platelets stimulated at different thrombin concentrations was studied. There was significantly higher adherence of stimulated platelets to nonconfluent cultures compared with confluent ones. This was confirmed by scanning electron microscopy, which also revealed a tendency for the platelets to adhere at the cell periphery. Electron microscopy also showed that thrombin-stimulated platelets induced endothelial cell contraction. Part of the peripheral endothelial cell surface toward the bottom of the culture dish was inverted, facing the lumen of the dish. This phenomenon was particularly seen in nonconfluent cultures. When⁵¹Cr-labeled endothelial cultures were incubated with a mildly injurious fluid as heparinized sodium acetate and 20% serum, at 20° C for 30 min, the nonconfluent cultures showed significantly more cell detachment and release of⁵¹Cr than the confluent ones. We conclude that under the conditions of the present experiments there are differences in the reactivity of confluent and nonconfluent endothelial cell cultures. These differences probably reflect biological dissimilarities. In experiments where properties of cultured endothelium are studied, care should be taken that the degree of confluency is standardized.     

大鼠脊髓诱发电位与脊髓损伤的关系——Ⅱ、皮肤、椎板和硬膜上诱发电位的比较

从大鼠的背侧皮肤表面和椎板分别记录刺激坐骨神经诱发的脊髓电位,并与硬膜上电位进行了比较。结果表明:皮肤表面电位与硬膜上直接记录具有相同的节段性特征。从硬膜上经椎板至皮肤表面、反应潜伏时延长、电位幅度递减。各波峰潜伏时也相应增加。电位的波形、幅度与记录方式有关,但反应潜伏时不受影响。     

Eye movements and the enhancement of edges

A mathematical examination of retinal photochemistry leads to a hypothesis for Mach band phenomena based on eye movements. This retinal model suggests why minimally distinct borders fade under eye fixation and agrees qualitatively with subjective measures of border contrast as a function of overall field luminance.Deceased     

Free radical damage to cultured porcine aortic endothelial cells and lung fibroblasts: Modulation by culture conditions

Summary Culture conditions modulating cell damage from xanthine plus xanthine oxidase-derived partially reduced oxygen species were studied. Porcine thoracic aorta endothelial cells and porcine lung fibroblasts were maintained in monolayer culture. Cells were prelabeled with⁵¹Cr before xanthine plus xanthine oxidase exposure. Endothelial cells showed 30 to 100% more lysis than fibroblasts and thus seemed more sensitive to this oxidant stress. The effect of cell culture age, as indicated by population doubling level (PDL), was examined. Response of low PDL endothelial cells and fibroblasts subjected to oxidant stress was compared with the response of PDL 15 cells. Both low PDL endothelial cells and fibroblasts responded differently to the lytic effect of xanthine oxidase-derived free radicals than did higher PDL cells. Specific activities of the antioxidant enzymes catalase, managanese superoxide dismutase, copper-zinc superoxide dismutase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase were measured in both low and high PDL fibroblasts and endothelial cells. Antioxidant enzyme specific activities could only partially explain the differences in response to oxidant stress between fibroblasts and endothelial cells and between low and high PDL cells. Cell culture medium composition modulated the rate of production, and relative proportions of xanthine plus xanthine oxidase-derived partially reduced species of oxygen, i.e. superoxide, hydrogen peroxide, and hydroxyl radical. Serum content of medium was important in modulating free radical generation; superoxide production rates decreased 32%, H₂O₂ became undetectable, and hydroxyl radical generation decreased 54% in the presence of 10% serum. The medium protein and iron content also modulated free radical generation. The data suggest that cell culture media constituents, cell type, and cell culture age greatly affect in vitro response of cells subjected to oxidant stress. Research supported by American Lung Association Fellowship Training Grant and Research Training Grant, the R. J. Reynolds Corporation, and National Institutes of Health Grants HL29784 and 1 HL 23805.     

125I] 3-quinuclidinyl 4-iodobenzilate: a high affinity, high specific activity radioligand for the M1 and M2-acetylcholine receptors

We have prepared a radioiodinated ligand which binds with high affinity to the muscarinic acetylcholine receptor (m-AChR). A derivative of 3-quinuclidinyl benzilate, [125I] labeled (R) 1-aza-bicyclo(2.2.2)oct-3-yl (R,S)-alpha-hydroxy-alpha-(4-[125I]iodophenyl)phenyl acetate (4- IQNB ) exhibits an affinity for the m-AChR from corpus striatum higher than that of (R) [3H] QNB. Additionally, [125I] 4- IQNB exhibits receptor selectivity for the M1 receptor since the affinity for the receptor from dog and rat heart is lower than that using dog or rat corpus striatum.     

Regulation of UDP-Galactose:Ceramide Galactosyltransferase and UDP-Glucose:Ceramide Glucosyltransferase After Crush and Transection Nerve Injury

The enzyme activities of ceramide galactosyltransferase and ceramide glucosyltransferase were assayed as a function of time (0, 1, 2, 4, 7, 14, 21, 28, and 35 days) after crush injury or permanent transection of the adult rat sciatic nerve. These experimental models of neuropathy are characterized by the presence and absence of axonal regeneration and subsequent myelin assembly. Within the first 4 days after both injuries, a 50% reduction of ceramide galactosyltransferase-specific activity was observed compared to values found in the normal adult nerve. This activity remained unchanged at 7 days after injury; however, by 14 days the ceramide galactosyltransferase activity diverged in the two models. The activity increased in the crushed nerve and reached control values by 21 days, whereas a further decrease was observed in the transected nerve such that the activity was nearly immeasurable by 35 days. In contrast, the ceramide glucosyltransferase activity showed a rapid increase between 1 and 4 days, followed by a plateau that was 3.4-fold greater than that in the normal adult nerve, which persisted throughout the observation period in both the crush and transection models. [3H]Galactose precursor incorporation studies at 7, 14, 21, and 35 days after injury confirmed the previously observed shift in biosynthesis from the galactocerebrosides during myelin assembly in the crush model to the glucocerebrosides and oligohexosylceramide homologues in the absence of myelin assembly in the transection model. The transected nerves were characterized by a peak of biosynthesis of the glucocerebrosides at 14 days. Of particular interest is the biosynthesis of the glucocerebrosides and the oligohexosylceramides at 7 and 14 days after crush injury.(ABSTRACT TRUNCATED AT 250 WORDS)     

巯基物质在消炎痛诱发大鼠胃粘膜损伤中的作用

本工作研究了巯基物质在消炎痛引起大鼠胃粘膜损伤中的可能作用。在胃粘膜损伤发生过程中、胃粘膜内非蛋白及蛋白结合的巯基物质含量均无明显降低。虽然半胱胺灌胃(132或264μmol)或皮下注射(132μmol)后均明显抑制消炎痛溃疡的发生,其抑制率分别为82％,92％和75％,但同样具有巯基的半胱氨酸却无保护作用。半胱胺(132μmol)皮下注射可使消炎痛大鼠胃酸分泌抑制46％,而灌胃则无此作用。两种途径给予的半胱胺均不影响胃壁结合粘液的分泌。这些结果表明,胃粘膜内巯基物质似不参与消炎痛的致溃疡过程。半胱胺在此种模型上虽有强烈的细胞保护作用,但似乎不是由于其分子上所带的巯基所致。因此,巯基物质在消炎痛引起的胃粘膜损伤模型上没有细胞保护作用。