Effect of tetanus toxin on the content of glycine, gamma-aminobutyric acid, glutamate, glutamine and aspartate in the rat spinal cord

Tetanus toxin injected intramuscularly induced no significant changes in the levels of glycine, GABA, glutamate, glutamine or aspartate in extracts of spinal cord from rats killed at timed intervals during the development of local and generalized tetanus. The amino acid contents in the hemisegment (longitudinal one-half) of the spinal cord (L₂-L₆) on the injected side (left gastrocnemius muscle) did not differ significantly from the contents in the hemisegment of the spinal cord on the non-injected side. Nor were there any consistent changes in the contents of the amino acids in either hemisegment of the spinal cord as the tetanic symptoms became progressively more severe. Hence, the amino acid pool in the spinal cord was relatively stable despite the metabolic changes known to occur in tetanus. Our observations are consistent with the view of Johnston , De Groat and CURTIS (1969) who suggested that if glycine were indeed a spinal inhibitory neurotransmitter released by interneurons affected by tetanus toxin, the toxin should interfere with the release of the amino acid rather than deplete the transmitter stores.     

Macroscopic-anatomic changes of the skull, spine, spinal cord, extremities and tails of postnatal growing albino rats

27 albino-rats were used to measure the growth of skull, spinal column, spinal cord, roots of the spinal nerves, and length of tail and extremities at their 1st to the 5th, the 8th, 11th, 15th, and 20th postnatal day. The growth rate of the distal and caudal parts of the distal body was higher than of the cranial and proximal ones.     

Alterations in Lipid Metabolism, Na+,K+-ATPase Activity, and Tissue Water Content of Spinal Cord Following Experimental Traumatic Injury

Traumatic spinal cord injury has recently been shown to cause a rapid increase in free fatty acids (FFAs) and lipid degradation in cats. The present studies report a more delayed, time-dependent increase in FFAs and a concomitant decrease in phospholipids following traumatic spinal injury in rats. The largest percentage increases were found for polyunsaturated fatty acids, particularly arachidonic acid. Associated with these changes were a reduction in the activity of Na+,K+-ATPase and development of spinal cord edema. These findings support the hypothesis that traumatic spinal cord injury leads to delayed, as well as early, hydrolysis of membrane phospholipids, resulting in the liberation of FFAs. Such changes may contribute to secondary spinal cord injury either through direct effects on membranes or through the actions of secondary metabolic products such as the eicosanoids. The latter may cause tissue injury by contributing to the reduction in spinal cord blood flow or through inflammatory responses that follow trauma.     

Some observations on habituation of the flexor reflex in the rat: the influence of strychnine, bicuculline, spinal transection, and decerebration

The involvement of inhibition in habituation of the flexor reflex was investigated in intact, spinal, and decerebrate rats. Strychnine and bicuculline were administered in order to determine the contribution of certain forms of central inhibition to the development of habituation. Both strychnine and bicuculline reduced habituation in the intact rat but did not do so in the spinal preparation. Strychnine, in fact, caused a facilitation of habituation in the spinal rat. The impairment of habituation by strychnine was related to the intensity of stimulation used to elicit the reflex. Thus, the effect of strychnine was only demonstrable when relatively high intensities were used. Flexor reflex habituation was shown to be more pronounced in the decerebrate than in the spinal preparation. This difference could be demonstrated only when stimuli of high intensity were given. It is concluded that, in the absence of supraspinal influences, habituation of the flexor reflex does not require inhibitory mechanisms. However, inhibition may play a role in habituation of the component of the reflex that utilizes descending influences.     

Effects of incomplete ischemia and subsequent recirculation on free palmitate, stearate, oleate and arachidonate levels in lumbar and cervical spinal cord of rabbit

The effect of severe incomplete ischemia, induced by abdominal aorta ligation for 40 minutes, and subsequent recirculation for one and four days on accumulation of free fatty acids was studies in the lumbar and cervical part of rabbit spinal cord. Changes in free fatty acid levels were determined separately in gracile fascicle (Fg), dorsal part (Dp, without Fg) and ventral part (Vp) of both spinal cord regions. In lumbar spinal cord increases in free fatty acid levels, especially that of arachidonate, were observed in Fg, Dp and Vp a the end of the ischemic period. During recirculation all values were similar to nonischemic controls. In cervical spinal cord a slight increase in free fatty acid levels was found in Fg after four days of recirculation, and in Dp arachidonate and stearate levels were most markedly elevated after one day of recirculation. No changes at any interval were found in Vp of cervical spinal cord. The present results indicate that the experimental insult induced typical ischemic injury to spinal cord tissue demonstrated by fatty acid liberation from membrane lipids. This injury may affect neurotransmission and other processes and free fatty acids themselves impair tissue metabolism (inhibition of oxidative phosphorylation, edema precipitation, synthesis of eicosanoids) and thus restrict the possibilities to enhance recovery in the recirculation period.     

血清pNF-H、NSE、ESR与老年脊柱手术患者病情和术后认知功能的相关性研究

摘要 目的：研究老年脊柱手术患者血清神经丝蛋白H磷酸化亚型（pNF-H）、神经元特异性烯醇化酶（NSE）以及红细胞沉降率（ESR）水平与患者病情以及术后认知功能障碍发生的相关性。方法：选取2017年6月到2021年6月在我院进行脊柱手术的老年患者82例,根据病情严重程度分为脊髓未损伤组（n=35）、脊髓不完全损伤组（n=27）和脊髓完全损伤组（n=20）,根据术后是否发生认知功能障碍（POCD）分为认知功能障碍组（POCD组,n=30）和无认知功能障碍组（No-POCD组,n=52）。比较各组患者术前和术后1天、3天、7天血清pNF-H、NSE和ESR水平。结果：（1）脊髓未完全损伤组患者血清pNF-H、NSE和ESR均显著高于脊髓未损伤组患者,而均显著低于脊髓完全损伤组患者（P<0.05）;（2）No-POCD组和POCD组在性别、年龄、体重、BMI、手术时间以及术中失血量均具有可比性（P>0.05）;（3）POCD组患者术前和术后1天、3天、7天血清pNF-H、NSE和ESR水平均显著高于No-POCD组患者（P<0.05）。结论：老年脊柱手术患者血清pNF-H、NSE和ESR水平与患者病情以及术后认知功能障碍发生有关,术前及术后血清pNF-H、NSE和ESR水平升高可能增加老年脊柱手术患者术后认知功能障碍风险,检测血清pNF-H、NSE和ESR水平有助于评估老年手术患者病情和术后认知功能障碍发生风险。     

Microiontophoresis of 5-hydroxytryptamine, epinephrine, and prostaglandin E1 on spinal neurons in the frog.

5-Hydroxytryptamine (5-HT) and epinephrine were applied by microiontophoresis to single neurons in the isolated spinal cord of the frog. 5-HT depressed all but two of the responsive cells, whereas the response to epinephrine consisted exclusively of depression. 5-HT action was more marked than that of epinephrine on most cells. With either compound, responseve units were diffusely distributed throughout the tissue. While it was proven that prostaglandin E1 (PGE1) exerts a direct excitatory action on spinal neurons, no evidence of an antagonism between PGE1 and the monoamines was obtained. These findings provide additional support to the hypothesis that 5-HT and epinephrine are transmitters in the frog spinal cord. The possibility that PGE1 may 'modulate' the responsiveness of spinal neurons to the monoamines was not confirmed.     

Heterogeneity of astrocytic membranes in the optic nerve and spinal cord of the lizard,Anolis carolinensis

Summary The architecture of astrocytic membranes in the optic nerve and the spinal cord of the lizard, Anolis carolinensis, was investigated by use of the freeze-fracturing technique. Whereas astrocytes in mammals reveal so-called orthogonal arrays of particles (OAPs) in their membranes, astrocytes in lower vertebrates lack these structures. This study demonstrates for the first time OAPs in astrocytes from a submammalian species. They were found commonly in the optic nerve and less frequently in the spinal cord. However, the OAPs in astrocytes of spinal cord were confined to midtrunk levels; the astrocytes in the caudal spinal cord failed to reveal OAPs.Additionally, the ependymal cells around the central canal did not show any OAPs, either in the thoracic or in the caudal spinal cord. They were interconnected by gap and tight junctions, which were not intercalated with each other.The findings support our current working hypothesis according to which the presence and absence of OAPs in astrocytes may be correlated with regenerative incapability or capability of CNS-structures; i.e., whereas the thoracic spinal cord in Anolis carolinensis is known to be incapable of regeneration after injury, the caudal spinal cord is regenerative.     

The mechanical properties of neonatal rat spinal cord in vitro,and comparisons with adult

A number of studies have investigated the mechanical properties of adult spinal cord under tension, however it is not known whether age has an effect on these properties. This is of interest to those aiming to understand the clinical differences between adults and children with spinal cord injury (e.g. severity and recovery), and those developing experimental or computational models for paediatric spinal cord injury. Entire spinal cords were freshly harvested from neonatal rats (14 days) and tested in vitro under uniaxial tension at a range of strain rates (0.2, 0.02, 0.002/s) to a range of strains (2%, 3.5%, 5%), with relaxation responses being recorded for 15 min. These mechanical properties were compared to previously reported data from similar experiments on adult rat spinal cords, and the peak stress and the stress after 15 min of relaxation were found to be significantly higher for spinal cords from adults than neonates (p<0.001). A non-linear viscoelastic model was developed and was observed to adequately predict the mechanical behaviour of this tissue. The model developed in this study may be of use in computational models of paediatric spinal cord. The significant differences between adult and neonatal spinal cord properties may explain the higher initial severity of spinal cord injury in children and may have implications for the development of experimental animal models for paediatric spinal cord injury, specifically for those aiming to match the injury severity with adult experimental models.     

Regional Distribution of Immunoreactive-Thyrotrophin-Releasing Hormone and Substance P, and Indoleamines in Human Spinal Cord

The regional distributions of thyrotrophin-releasing hormone (TRH) and substance P in postmortem human spinal cord were determined by radioimmunoassay in fresh tissue taken from 22 patients who died without known neurological disease. Dorsal, ventral, and intermediolateral spinal cord regions were obtained from different segmental levels (lumbar L1, 2, 3, and 4; thoracic groups T1-3, T4-6, T7-9, and T10-12) together with selective regions of grey matter of lumbar spinal cord. The effects on peptide levels of the age of the patient, the postmortem time interval, and freezing the tissue samples prior to assay were assessed. Levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in regional lumbar and thoracic tissue using HPLC with electrochemical detection. Substance P was found in the highest concentration in the dorsal spinal cord, with no significant segmental differences. In contrast, TRH was present in higher levels in the ventral rather than the dorsal spinal cord, with segmental differences. There was a significant difference in the 5-HT/5-HIAA ratio between dorsal and ventral spinal cord, with the highest ratio in the ventral spinal cord. There were no significant differences in substance P, TRH, or 5-HT levels in spinal cords between 5 and 20 h postmortem or from patients aged between 65 and 90 years. Freezing the tissue (-80 degrees C for 24 h) prior to assay significantly reduced TRH and substance P levels compared to samples assayed immediately without prior freezing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Raised Thyrotrophin-Releasing Hormone, Pyroglutamylamino Peptidase, and Proline Endopeptidase Are Present in the Spinal Cord of Wobbler Mice but Not in Human Motor Neurone Disease

The Wobbler mouse (wr) is a mutant that exhibits loss of anterior horn cells in the spinal cord and brainstem and subsequent muscle wasting, particularly of the forelimbs and neck. The wr mice, 2-3 months of age, were found to have increased levels of immunoreactive-thyrotrophin-releasing hormone (ir-TRH) in the spinal cord and pons and medulla, but not in other CNS areas. This increase was observed in dorsal and ventral cord and at cervical, thoracic, and lumbar levels and was confirmed by HPLC to be authentic TRH. The levels of immunoreactive-somatostatin, -neurotensin, and -substance P were not raised in the CNS of wr mice. The activities of two peptidases capable of degrading TRH, pyroglutamylaminopeptidase (PGAP, EC 3.4.11.8) and proline endopeptidase (PEP, EC 3.4.21.26), and the level of 5-hydroxyindoleacetic acid were also raised in the spinal cord of 2-3-month-old wr mice although the activities of alanine aminopeptidase and lactate dehydrogenase and the level of 5-hydroxytryptamine were not. Increased spinal cord levels of ir-TRH and PGAP and PEP activities were not observed in the 1-month-old wr mice. In addition, a pilot study using spinal cord obtained at autopsy from three patients with motor neurone disease and 12 control subjects indicated no increase in spinal cord ir-TRH, PGAP, or PEP in human motor neurone disease.     

去甲肾上腺素,甘氨酸,γ—氨基丁酸和L—谷氨酸对节段性与下行性...

Noradrenaline (NE), glucine (GLY), gamma-aminobutyric acid (GABA) and L-glutamic acid (L-GLU) were locally applied to the dorsal surface of lumbar spinal cord on anesthetized and immobilized rats and their effects on segmental (SP) and descending (DP) spinal field potentials were examined. Both waves N and P of SP and DP were reduced markedly in amplitudes following local application of NE. A significant decrease in amplitude of wave N and a remarkable increase in wave P in both SP and DP were shown during the application of GLY, GABA and L-GLU. The results suggest that these neurotransmitters may be involved in the generation of waves N and P, particularly affecting the activities of interneurons in the spinal dorsal horn.     

Comparison of mu, delta, and kappa opiate binding sites in rat brain and spinal cord

The binding characteristics of mu, delta, and kappa opiate sites were studied in rat brain and spinal cord membrane homogenates. Scatchard analysis of 3H-Dihydromorphine, 3H-D-Ala2-D-Leu5-Enkephalin (in the presence of morphiceptin), and 3H-Ethylketocyclazocine (in the presence of morphiceptin and D-Ala2-D-Leu5-Enkephalin) binding sites revealed similar high affinities of these ligands for their respective sites in brain and spinal cord. The majority of binding in brain and spinal cord was attributed to mu and delta sites, with only about 10% of the combined total binding capacity being kappa.     

The colour change of the minnow, Phoxinus phoxinus with particular reference to the effect of spinal lesions

An account is given of the anatomy of the spinal cord of the minnow, Phoxinus phoxinus L., and comparisons are made with the spinal cords of other teleosts. The effects on the rapid, neurally controlled colour responses of complete transection of the spinal cord at different levels indicated that, in the particular fish used for this work, the sympathetic pigmento-motor fibres had a localized outflow from the spinal cord around vertebra 13. Partial lesions of the spinal cord at vertebrae 3, 4, 10 and 11 and their effects on the colour responses indicated that, at these spinal levels, the pigmento-motor fibres were dorsomedially located within the dorsal horns. Complete and partial transection of the spinal cord at any single level between vertebrae 12 and 14 and partial transection of the dorsomedial spinal tissues at vertebrae 3, 4, 10 and 11 resulted in differential paling of the entire dorsolateral skin of the fish in response to a change of background from black to white. It would appear that in both cases this differential response of the melanophores was the result of transecting a proportion of the spinal pigmento-motor fibres.     

The development of motoneurons in the embryonic spinal cord of the mouse mutant, muscular dysgenesis (mdg/mdg): survival, morphology, and biochemical differentiation

Motoneuron development was studied in the spinal cord of the mouse mutant, muscular dysgenesis, between embryonic days (E) 13 and 18. Dysgenic embryos are characterized by the absence of neuromuscular activity (motility) and exhibit a number of other striking changes in neuromuscular development. Many of these changes have also been observed in chick embryos chronically treated with neuromuscular blocking agents that suppress motility. Motoneuron survival, as well as several other aspects of neuronal development, was examined in the thoracic and lumbar spinal cords of mutant and control embryos. There was a significant decrease in motoneuron numbers in control embryos indicating the presence of naturally occurring cell death in the mouse spinal cord. At all ages examined, the dysgenic embryos had significantly more healthy and significantly fewer degenerating motoneurons than controls. There were no differences in the number of dorsal root ganglion neurons or in any of the other morphometric parameters examined between mutant and control embryos. Creatine kinase activity, a marker for myofiber maturation, was significantly reduced in the limb musculature of mutant embryos. Choline acetyltransferase activity was significantly increased in the spinal cord of mutant embryos. No significant differences were observed in spinal cord levels of acetylcholinesterase activity between control and mutant embryos. The absence of muscle contractions in the dysgenic mouse is associated with a number of changes in neuromuscular development, including a substantial reduction of naturally occurring motoneuron death.     

Gas chromatographic analysis of free amino acids in the hyaloplasm of the hypophysis, pineal gland, thyroid gland, spinal cord, thymus and lymph nodes of the cow

Studies of the qualitative and quantitative composition of free amino acids in the hyaloplasm of the hypophysis, pineal gland, thyroid gland, spinal cord, thymus and lymph nodes of the cow are described. The following findings are reported: the highest levels of alanine, valine, glycine, isoleucine, histidine, leucine, threonine, serine, phenylalanine, tyrosine and lysine are found in the thyroid gland, methionine and aspartic acid in the spinal cord, tryptophan and hydroxyproline in the pineal gland, and proline and glutamic acid in the thymus gland. The highest level by weight is that of glutamic acid in all tissues. The presence of α-aminobutyric acid combined with sarcosine and 4-aminoisobutyric acid with 2-AOA and citrulline with cystine was demonstrated. α-Aminoisobutyric acid and isovaline were found in the spinal cord.     

Nicotine protects against arachidonic-acid-induced caspase activation, cytochrome c release and apoptosis of cultured spinal cord neurons

Hydrolysis of membrane phospholipids of spinal cord neurons is one of the first events initiated in spinal cord trauma. In this process, free fatty acids, and in particular arachidonic acid, are released. Exposure of spinal cord neurons to free arachidonic acid can compromise cell survival and initiate apoptotic cell death. In order to determine potential mechanisms of apoptosis induced by arachidonic acid, activation of caspases -3, -8, and -9, as well as the release of cytochrome c into the cytoplasm were measured in cultured spinal cord neurons exposed to 10 microM of this fatty acid. In addition, because nicotine can exert a variety of neuroprotective effects, we hypothesized that it can prevent arachidonic acid induced apoptosis of spinal cord neurons. To study this hypothesis, spinal cord neurons were pretreated with nicotine (10 microM for 2 h) before arachidonic acid exposure and caspase activation as well as markers of apoptotic cell death were studied. Treatment of spinal cord neurons with arachidonic acid for up to 24 h significantly increased cytoplasmic levels of cytochrome c, induced caspase activation and induced DNA laddering, a hallmark of apoptotic cell death. Nicotine pretreatment markedly attenuated all these effects. In addition, antagonist studies suggest that the alpha7 nicotinic receptor is primarily responsible for these anti-apoptotic effects of nicotine. These results indicate that nicotine can exert potent neuroprotective effects by inhibiting arachidonic acid induced apoptotic cascades of spinal cord neurons.     

Spatiotemporal Changes of NGF,BDNF and NT-3 in the Developing Spinal Cords of Embryonic Chicken

Spatiotemporal changes of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in the spinal cords of chick embryonic stage day 7 (E7) and day 14 (E14) were examined by using immunohistochemistry and Western blot. Intensive NGF immunoreaction (IR) was detected in the white matter of the spinal cords, while BDNF-IR in perikaryon and neurite, and NT-3-IR in the nucleus and cytoplasm were seen in the neurons of the ventral horn in the gray matter. Comparatively, the expressions for three growth factors have expanded largely into the dorsal horn at E14, and the level of proteins for these growth factors increased significantly in the spinal cords from E7 to E14. Morphological observation showed that the lumbar spinal cords of E7 appeared rectangular, whereas it gave a butterfly shape in the gray matter consisting of the typical ventral horn, dorsal horn and intermediate zone at E14. The present findings indicated that the spatiotemporal changes of NGF, BDNF and NT-3 could be associated to the morphological changes of developing spinal cords, suggesting the possible roles of three growth factors in the development of spinal cords.     

Bombesin-like peptides in rat spinal cord: Biochemical characterization,localization and mechanism of release

Bombesin-like peptides were characterized in rat spinal cord by radio-immunoassay. The density of bombesin-like peptides was eight-fold greater in the dorsal than ventral horn or white matter of the spinal cord. Using high pressure liquid chromatography fractionation techniques, the main peak of immunoreactivity coeluted with synthetic bombesin. Also, the mechanism of release spinal cord peptides was determined. K⁺ and veratridine stimulated release of immunoreactive bombesin in a Ca⁺⁺-dependent mechanism. These data indicate that bombesin-like peptides may function as a unique class of neuroregulatory agents in mammalian spinal cord.     

Nitric oxide synthase and interferon-gamma receptor immunoreactivities in relation to ascending spinal pathways to thalamus, hypothalamus, and the periaqueductal grey in the rat

The retrograde tracer fluoro-gold was injected into the periaqueductal grey, thalamus or hypothalamus, and spinal cord sections were processed for neuronal nitric oxide synthase (nNOS) immunohistochemistry to investigate the relationships of nNOS immunoreactive, and spinomesencephalic, spinothalamic and spinohypothalamic projection neurones. In addition, in the lateral spinal nucleus the relationship between spinomesencephalic, -thalamic and -hypothalamic projection neurones, and nNOS and interferon-gamma receptor immunoreactive structures was investigated at the lumbar level. No single retrogradely labelled spinomesencephalic, -thalamic or -hypothalamic neurone showed nNOS immunoreactivity. In the lateral spinal nucleus, however, many fluoro-gold-labelled neurones were closely apposed by both nNOS and interferon-gamma receptor immunoreactive structures, especially prominent in the hypothalamic injection cases. This study gave no evidence for nNOS immunoreactivity in spinal neurones projecting to the periaqueductal grey, thalamus or hypothalamus, but suggests that in the lateral spinal nucleus such neurones are contacted by both nNOS- and interferon-gamma receptor-containing axon terminals.