The inhibitory effects of nitrous oxide and methylmercury in vivo on methionine synthase (EC 2.1.1.13) activity in the brain, liver, ovary and spinal cord of the rat

1989 ◽  
Vol 20 (4) ◽  
pp. 427-431 ◽  
Author(s):  
Charles E. Brennt ◽  
John R. Smith
Keyword(s):  
Spinal Cord ◽  
Nitrous Oxide ◽  
Methionine Synthase ◽  
Inhibitory Effects ◽  
The Brain

scholarly journals Recapitulate development to promote axonal regeneration: good or bad approach?

2006 ◽  
Vol 361 (1473) ◽  
pp. 1565-1574 ◽  
Author(s):  
Marie T Filbin
Keyword(s):  
Spinal Cord ◽  
Axonal Regeneration ◽  
Molecular Level ◽  
Signal Transduction Pathway ◽  
Developmental Changes ◽  
Transduction Pathway ◽  
The Past ◽  
Brain And Spinal Cord ◽  
The Brain

In the past decade there has been an explosion in our understanding, at the molecular level, of why axons in the adult, mammalian central nervous system (CNS) do not spontaneously regenerate while their younger counterparts do. Now a number of inhibitors of axonal regeneration have been described, some of the receptors they interact with to transduce the inhibitory signal are known, as are some of the steps in the signal transduction pathway that is responsible for inhibition. In addition, developmental changes in the environment and in the neurons themselves are also now better understood. This knowledge in turn reveals novel, putative sites for drug development and therapeutic intervention after injury to the brain and spinal cord. The challenge now is to determine which of these putative treatments are the most effective and if they would be better applied in combination rather than alone. In this review I will summarize what we have learnt about these molecules and how they signal. Importantly, I will also describe approches that have been shown to block inhibitors and encourage regeneration in vivo . I will also speculate on what the differences are between the neonatal and adult CNS that allow the former to regenerate and the latter not to.

scholarly journals Nitrous Oxide Impairs Axon Regeneration after Nervous System Injury in Male Rats

2019 ◽  
Vol 131 (5) ◽  
pp. 1063-1076
Author(s):  
Krista J. Stewart ◽  
Bermans J. Iskandar ◽  
Brenton M. Meier ◽  
Elias B. Rizk ◽  
Nithya Hariharan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Nitrous Oxide ◽  
Folic Acid ◽  
Functional Recovery ◽  
Axon Regeneration ◽  
Retinal Ganglion ◽  
Cord Injury

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Nitrous oxide can induce neurotoxicity. The authors hypothesized that exposure to nitrous oxide impairs axonal regeneration and functional recovery after central nervous system injury. Methods The consequences of single and serial in vivo nitrous oxide exposures on axon regeneration in four experimental male rat models of nervous system injury were measured: in vitro axon regeneration in cell culture after in vivo nitrous oxide administration, in vivo axon regeneration after sharp spinal cord injury, in vivo axon regeneration after sharp optic nerve injury, and in vivo functional recovery after blunt contusion spinal cord injury. Results In vitro axon regeneration 48 h after a single in vivo 70% N2O exposure is less than half that in the absence of nitrous oxide (mean ± SD, 478 ± 275 um; n = 48) versus 210 ± 152 um (n = 48; P < 0.0001). A single exposure to 80% N2O inhibits the beneficial effects of folic acid on in vivo axonal regeneration after sharp spinal cord injury (13.4 ± 7.1% regenerating neurons [n = 12] vs. 0.6 ± 0.7% regenerating neurons [n = 4], P = 0.004). Serial 80% N2O administration reverses the benefit of folic acid on in vivo retinal ganglion cell axon regeneration after sharp optic nerve injury (1277 ± 180 regenerating retinal ganglion cells [n = 7] vs. 895 ± 164 regenerating retinal ganglion cells [n = 7], P = 0.005). Serial 80% N2O exposures reverses the benefit of folic acid on in vivo functional recovery after blunt spinal cord contusion (estimate for fixed effects ± standard error of the estimate: folic acid 5.60 ± 0.54 [n = 9] vs. folic acid + 80% N2O 5.19 ± 0.62 [n = 7], P < 0.0001). Conclusions These data indicate that nitrous oxide can impair the ability of central nervous system neurons to regenerate axons after sharp and blunt trauma.

scholarly journals Xenon Has Greater Inhibitory Effects on Spinal Dorsal Horn Neurons than Nitrous Oxide in Spinal Cord Transected Cats

1999 ◽  
Vol 88 (4) ◽  
pp. 893-897 ◽  
Author(s):  
Yoshiya Miyazaki ◽  
Takehiko Adachi ◽  
Jun Utsumi ◽  
Tsutomu Shichino ◽  
Hajime Segawa
Keyword(s):  
Spinal Cord ◽  
Nitrous Oxide ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Inhibitory Effects ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Spinal Dorsal Horn Neurons

scholarly journals Xenon Has Greater Inhibitory Effects on Spinal Dorsal Horn Neurons than Nitrous Oxide in Spinal Cord Transected Cats

1999 ◽  
Vol 88 (4) ◽  
pp. 893-897 ◽  
Author(s):  
Yoshiya Miyazaki ◽  
Takehiko Adachi ◽  
Jun Utsumi ◽  
Tsutomu Shichino ◽  
Hajime Segawa
Keyword(s):  
Spinal Cord ◽  
Nitrous Oxide ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Inhibitory Effects ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Spinal Dorsal Horn Neurons

Neuronal inhibitory effects of methadone are predominantly opioid receptor mediated in the rat spinal cord in vivo

2000 ◽  
Vol 4 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Katherine J. Carpenter ◽  
Victoria Chapman ◽  
Anthony H. Dickenson
Keyword(s):  
Spinal Cord ◽  
Opioid Receptor ◽  
Inhibitory Effects ◽  
Rat Spinal Cord

GABAergic Interneurons at Supraspinal and Spinal Levels Differentially Modulate the Antinociceptive Effect of Nitrous Oxide in Fischer Rats

2003 ◽  
Vol 98 (5) ◽  
pp. 1223-1230 ◽  
Author(s):  
Ryo Orii ◽  
Yoko Ohashi ◽  
Sunil Halder ◽  
Mariangela Giombini ◽  
Mervyn Maze ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Nitrous Oxide ◽  
Antinociceptive Effect ◽  
Gabaergic Neurons ◽  
Inhibitory Neurons ◽  
Gamma Aminobutyric Acid ◽  
Gaba A ◽  
Fischer Rats ◽  
The Brain ◽  
Gas Exposure

Background The study hypothesizes that nitrous oxide (N(2)O) releases opioid peptide in the brain stem, which results in inhibition of gamma-aminobutyric acid-mediated (GABAergic) neurons that tonically inhibit the descending noradrenergic inhibitory neurons (DNIN), resulting in activation of DNIN. In the spinal cord, activation of DNIN leads to the release of norepinephrine, which inhibits nociceptive processing through direct activation of alpha2 adrenoceptor and indirect activation of GABAergic neurons through alpha1 adrenoceptor. Arising from this hypothesis, it follows that GABAergic neurons will modulate the antinociceptive effect of N(2)O in diametrically opposite directions at supraspinal and spinal levels. The authors have tested this tenet and further examined the effect of midazolam, a GABA-mimetic agent, on N(2)O-induced antinociceptive effect. Methods Adult male Fischer rats were administered muscimol (GABA(A) receptor agonist) intracerebroventricularly (icv), gabazine (GABA(A) receptor antagonist) intrathecally (intrathecal), or midazolam intraperitoneally (intraperitoneal). Fifteen minutes later, they were exposed to air or 75% N(2)O and were subjected to the plantar test after 30 min of gas exposure. In some animals administered with midazolam, gas exposure was continued for 90 min, and the brain and spinal cord were examined immunohistochemically. Results The N(2)O-induced antinociceptive effect, which was attenuated by icv muscimol, intrathecal gabazine, and intraperitoneal midazolam. Midazolam inhibited N(2)O-induced c-Fos expression (a marker of neuronal activation) in the pontine A7 and spinal cord. Conclusions The GABAergic neurons modulate the antinociceptive effect of N(2)O in opposite directions at supraspinal and spinal levels. The pronociceptive effects of enhancement at the supraspinal GABAergic site predominate in response to systemically administered midazolam.

Demonstration of Hypomethylation of Proteins in the Brain of Pigs (but Not in Rats) Associated with Chronic Vitamin B12 Inactivation

1995 ◽  
Vol 88 (4) ◽  
pp. 471-477 ◽  
Author(s):  
M. McKeever ◽  
A. Molloy ◽  
P. Young ◽  
S. Kennedy ◽  
D. G. Kennedy ◽  
...  
Keyword(s):  
Nitrous Oxide ◽  
Methionine Synthase ◽  
Nerve Tissue ◽  
Subacute Combined Degeneration ◽  
Vitro Assay ◽  
Clinically Normal ◽  
Critical Components ◽  
The Brain ◽  
Methylation Ratio

1. Pigs treated with nitrous oxide for periods of 1, 2 and 4 months demonstrated markedly reduced levels of methionine synthase and concomitant reduction in the ratio of S-adenosylmethionine to S-adenosylhomocysteine, the methylation ratio, at all time intervals. 2. Both ‘O’ and ‘N’ methylations were significantly reduced in pigs after 4 months in nitrous oxide but not after shorter periods. 3. Hypomethylation correlated with the development of clinical ataxia, but was absent when the pigs were clinically normal. It also only occurred when the S-adenosylmethionine level fell. 4. Rats maintained in nitrous oxide for 4 months showed a marked reduction of methionine synthase but no reduction in the methylation ratio or in brain hypomethylation. None of the rats became clinically ataxic. 5. Using an exogenous protein as a methyl group acceptor, it was demonstrated in an in vitro assay that the methyltransferase enzymes responsible for brain ‘O’ and ‘N’ methylation were not affected per se by nitrous oxide treatment. 6. It is concluded that reduction of the methylation ratio in the brain of pigs as a consequence of methionine synthase inhibition leads to brain hypomethylation. This hypomethylation could affect critical components of nerve tissue, inducing the vacuolar myelopathic changes seen in the spinal cord of these animals, which mimic those of subacute combined degeneration in man.

Presynaptic and Interactive Peptidergic Modulation of Reticulospinal Synaptic Inputs in the Lamprey

2000 ◽  
Vol 83 (5) ◽  
pp. 2497-2507 ◽  
Author(s):  
David Parker
Keyword(s):  
Spinal Cord ◽  
Brain Stem ◽  
Peptide Yy ◽  
Input Resistance ◽  
Ventral Root ◽  
Interactive Effects ◽  
Inhibitory Effects ◽  
Spinal Neurons ◽  
Root Responses ◽  
The Brain

The modulatory effects of neuropeptides on descending inputs to the spinal cord have been examined by making paired recordings from reticulospinal axons and spinal neurons in the lamprey. Four peptides were examined; peptide YY (PYY) and cholecystokinin (CCK), which are contained in brain stem reticulospinal neurons, and calcitonin-gene–related peptide (CGRP) and neuropeptide Y (NPY), which are contained in primary afferents and sensory interneurons, respectively. Each of the peptides reduced the amplitude of monosynaptic reticulospinal-evoked excitatory postsynaptic potentials (EPSPs). The modulation appeared to be presynaptic, because postsynaptic input resistance and membrane potential, the amplitude of the electrical component of the EPSP, postsynaptic responses to glutamate, and spontaneous miniature EPSP amplitudes were unaffected. In addition, none of the peptides affected the pattern of N-methyl-d-aspartate (NMDA)–evoked locomotor activity in the isolated spinal cord. Potential interactions between the peptides were also examined. The “brain stem peptides” CCK and PYY had additive inhibitory effects on reticulospinal inputs, as did the “sensory peptides” CGRP and NPY. Brain stem peptides also had additive inhibitory effects when applied with sensory peptides. However, sensory peptides increased or failed to affect the amplitude of reticulospinal inputs in the presence of the brain stem peptides. These interactive effects also appear to be mediated presynaptically. The functional consequence of the peptidergic modulation was investigated by examining spinal ventral root responses elicited by brain stem stimulation. CCK and CGRP both reduced ventral root responses, although in interaction both increased the response. These results thus suggest that neuropeptides presynaptically influence the descending activation of spinal locomotor networks, and that they can have additive or novel interactive effects depending on the peptides examined and the order of their application.

scholarly journals Cerebrospinal fluid drainage kinetics across the cribriform plate are reduced with aging

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Molly Brady ◽  
Akib Rahman ◽  
Abigail Combs ◽  
Chethana Venkatraman ◽  
R. Tristan Kasper ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cerebrospinal Fluid ◽  
Subarachnoid Space ◽  
Ex Vivo ◽  
Cribriform Plate ◽  
Cervical Lymph Nodes ◽  
Spinal Subarachnoid Space ◽  
Ex Vivo Tissues ◽  
The Brain

Abstract Background Continuous circulation and drainage of cerebrospinal fluid (CSF) are essential for the elimination of CSF-borne metabolic products and neuronal function. While multiple CSF drainage pathways have been identified, the significance of each to normal drainage and whether there are differential changes at CSF outflow regions in the aging brain are unclear. Methods Dynamic in vivo imaging of near infrared fluorescently-labeled albumin was used to simultaneously visualize the flow of CSF at outflow regions on the dorsal side (transcranial and -spinal) of the central nervous system. This was followed by kinetic analysis, which included the elimination rate constants for these regions. In addition, tracer distribution in ex vivo tissues were assessed, including the nasal/cribriform region, dorsal and ventral surfaces of the brain, spinal cord, cranial dura, skull base, optic and trigeminal nerves and cervical lymph nodes. Results Based on the in vivo data, there was evidence of CSF elimination, as determined by the rate of clearance, from the nasal route across the cribriform plate and spinal subarachnoid space, but not from the dorsal dural regions. Using ex vivo tissue samples, the presence of tracer was confirmed in the cribriform area and olfactory regions, around pial blood vessels, spinal subarachnoid space, spinal cord and cervical lymph nodes but not for the dorsal dura, skull base or the other cranial nerves. Also, ex vivo tissues showed retention of tracer along brain fissures and regions associated with cisterns on the brain surfaces, but not in the brain parenchyma. Aging reduced CSF elimination across the cribriform plate but not that from the spinal SAS nor retention on the brain surfaces. Conclusions Collectively, these data show that the main CSF outflow sites were the nasal region across the cribriform plate and from the spinal regions in mice. In young adult mice, the contribution of the nasal and cribriform route to outflow was much higher than from the spinal regions. In older mice, the contribution of the nasal route to CSF outflow was reduced significantly but not for the spinal routes. This kinetic approach may have significance in determining early changes in CSF drainage in neurological disorder, age-related cognitive decline and brain diseases.

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