scholarly journals Afferent Responses During Experimentally Induced Semicircular Canalithiasis

2007 ◽  
Vol 97 (3) ◽  
pp. 2355-2363 ◽  
Author(s):  
Suhrud M. Rajguru ◽  
Richard D. Rabbitt

Benign paroxysmal positional vertigo (BPPV) is a common vestibular disorder that results in brief periods of vertigo and nystagmus, when the head is tipped relative to gravity. Symptoms are commonly attributed to the pathological presence of heavy calcium carbonate particles within the lumen of the semicircular canal(s)—a condition termed canalithiasis. In the present work, we induced canalithiasis in an animal model (oyster toadfish, Opsanus tau) by introducing heavy glass microbeads into the lumen of the lateral semicircular canal. Bead movement under the action of gravity and canal afferent nerve discharge were recorded in vivo. When the head was oriented nose-down, beads moved toward the nose and the lateral canal afferent discharge rate increased. Afferents that normally encoded angular velocity during oscillatory head rotations responded with tonic increases in the discharge rate during gravity-dependent bead movement. Other afferents, such as the units that rapidly adapt to a step increase in angular head velocity, responded with an initial increase in discharge rate followed by a period of adaptation. Afferent responses occurred in the complete absence of head movement and quantify the pathological inputs to the brain that arise from canalithiasis. The magnitude and time course of the responses reported here are sufficient to explain the symptoms of BPPV.

1987 ◽  
Vol 114 (3) ◽  
pp. 449-458 ◽  
Author(s):  
R. J. Omeljaniuk ◽  
S. H. Shih ◽  
R. E. Peter

ABSTRACT Dopamine acts directly on the pituitary to modulate gonadotrophin (GtH) secretion in goldfish (Carassius auratus). In the light of this important role for dopamine in the regulation of goldfish reproduction, this investigation was designed to evaluate the receptor specificity of this dopamine inhibition and to describe the use of domperidone, a specific dopamine D2-receptor antagonist, in the manipulation of pituitary function in goldfish. To investigate the specificity of dopamine inhibition of GtH secretion, selected dopamine receptor antagonists were injected i.p. to block dopamine receptors thereby increasing GtH secretion as reflected by increased serum concentrations of GtH. Serum GtH levels were significantly increased by the active stereoisomer (−)-sulpiride in a dose-related fashion; (+)-sulpiride had no effect. Comparison of dopamine antagonists at low doses indicated that only domperidone and pimozide caused significant increases in serum concentrations of GtH. Dopamine antagonists potentiated the action of a gonadotrophin-releasing hormone analogue (GnRH-A) with an order of potency of domperidone = pimozide > metoclopramide = fluphenazine. [3H]Domperidone, injected i.p. with unlabelled domperidone, entered the blood and achieved maximum concentrations 12 h after injection, but did not accumulate in the brain in appreciable amounts. Gonadal 3H radioactivity was usually equal to or in excess of blood radioactivity, while [3H]domperidone was highly concentrated in the pituitary in a time-dependent fashion, with maximal accumulation occurring 24 h after injection. The time-course of pituitary accumulation of [3H]domperidone correlated well with the temporal increase in serum GtH levels in response to i.p. injected domperidone or domperidone plus an analogue of LHRH. Domperidone increased serum concentrations of GtH in a dose-related fashion; an analogue of salmon GnRH (sGnRH-A) increased the sensitivity and magnitude of the serum GtH response to domperidone. Serum concentrations of GtH were increased by sGnRH-A in a dose-related fashion; a low dose of domperidone substantially increased the sensitivity of the serum GtH response to sGnRH-A. These results indicate that dopamine inhibits GtH secretion from the goldfish pituitary by acting through a specific mechanism mediated by a dopamine D2 receptor. Domperidone increased serum concentrations of GtH, potentiated the action of gonadotrophin-releasing hormones and did not pass into the brain after i.p. injection into goldfish. The data also suggest that dopamine and GnRH, although acting through different receptors, influence the effect of each other on GtH release. J. Endocr. (1987) 114, 449–458


BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Andrew L. Garfoot ◽  
Gary M. Wilson ◽  
Joshua J. Coon ◽  
Laura J. Knoll

Abstract Background The protozoan pathogen Toxoplasma gondii has the unique ability to develop a chronic infection in the brain of its host by transitioning from the fast growing tachyzoite morphology to latent bradyzoite morphology. A hallmark of the bradyzoite is the development of neuronal cysts that are resilient against host immune response and current therapeutics. The bradyzoite parasites within the cyst have a carbohydrate and protein-rich wall and a slow-replication cycle, allowing them to remain hidden from the host. The intracellular, encysted lifestyle of T. gondii has made them recalcitrant to molecular analysis in vivo. Results Here, we detail the results from transcriptional and proteomic analyses of bradyzoite-enriched fractions isolated from mouse brains infected with T. gondii over a time course of 21 to 150 days. The enrichment procedure afforded consistent identification of over 2000 parasitic peptides from the mixed-organism sample, representing 366 T. gondii proteins at 28, 90, and 120 day timepoints. Deep sequencing of transcripts expressed during these three timepoints revealed that a subpopulation of genes that are transcriptionally expressed at a high level. Approximately one-third of these transcripts are more enriched during bradyzoite conditions compared to tachyzoites and approximately half are expressed at similar levels during each phase. The T. gondii transcript which increased the most over the course of chronic infection, sporoAMA1, shows stage specific isoform expression of the gene. Conclusions We have expanded the transcriptional profile of in vivo bradyzoites to 120 days post-infection and provided the first in vivo proteomic profile of T. gondii bradyzoites. The RNA sequencing depth of in vivo bradyzoite T. gondii was over 250-fold greater than previous reports and allowed us to identify low level transcripts and a novel bradyzoite-specific isoform of sporoAMA1.


1976 ◽  
Vol 230 (2) ◽  
pp. 543-552 ◽  
Author(s):  
ME Raichle ◽  
JO Eichling ◽  
MG Straatmann ◽  
MJ Welch ◽  
KB Larson ◽  
...  

The extraction of 11C-labeled methanol, ethanol, and isopropanol, as well as 15O-labeled water by the brain during a single capillary transit, was studied in vivo in six adult rhesus monkeys by external detection of the time course of these tracers subsequent to their internal carotid artery injection. The data demonstrate the feasibility of accurately measuring brain permeability of highly diffusible substances by this technique and show that neither water nor the alcohols studied freely equilibrate with brain when the cerebral blood flow exceeds 30 ml/100 g min-1. At a cerebral blood flow of 50 ml/100 g min-1 only about 93% of an injected bolus of labeled water freely exchanges with brain, compared with methanol (93%), ethanol (97%), and isopropanol (99%). The brain capillary permeability-surface area (PS) products computed from these data were 0.023 cm3/s g-1 (water), 0.024 cm3/s g-1 (methanol), 0.030 cm3/s g-1 (ethanol), and 0.062 cm3/s g-1 (isopropanol). This sequence of PS products is consistent with the individual lipid solubilities of the alcohols studied and underscores the unique brain permeability characteristics of lipid-insoluble water.


1997 ◽  
Vol 272 (1) ◽  
pp. H176-H185 ◽  
Author(s):  
P. He ◽  
B. Liu ◽  
F. E. Curry

To investigate the mechanism whereby nitric oxide (NO) signaling pathways regulate microvessel permeability in vivo, we measured changes in microvessel hydraulic conductivity (Lp) and endothelial cytoplasmic calcium concentration ([Ca2+]i) in response to calcium ionophore, ionomycin (5 microM), and ATP (10 microM) before and after the use of NO synthase (NOS) inhibitors in single perfused frog mesenteric venular microvessels. Ionomycin induced a transient increase in endothelial [Ca2+]i and an associated increase in Lp. The NOS inhibitors N omega-nitro-L-arginine methyl ester (10 and 300 microM) and N omega-monomethyl-L-arginine (L-NMMA; 10, 50, and 100 microM) significantly attenuated the peak increase in Lp induced by ionomycin. A similar inhibitory effect was also observed with the increase in Lp mediated by ATP. In contrast, D-NMMA, a biologically inactive isomer of L-NMMA, showed no effect on ionomycin-induced increase in Lp L-Arginine (3 mM) reversed the inhibitory effect of L-NMMA (10 microM) on Lp. However, the NOS inhibitors did not alter the magnitude and time course of the biphasic increase in endothelial [Ca2+]i induced by both ionomycin and ATP. These data suggest that 1) calcium-dependent NO release is a necessary step to increase microvessel permeability, and 2) the action of NOS inhibitors in attenuating the permeability increase in response to ionomycin and ATP occurs down-stream from calcium entry and does not involve modification of the initial increase in endothelial [Ca2+]i.


1983 ◽  
Vol 244 (5) ◽  
pp. R611-R614 ◽  
Author(s):  
A. Niijima ◽  
A. Fukuda ◽  
T. Taguchi ◽  
J. Okuda

Afferent discharges were recorded from the nerve filaments dissected from the hepatic branch of the vagus nerve in the guinea pig. Recordings were made in isolated and perfused liver preparations and in vivo to study the effect of alpha and beta anomers of D-glucose on the afferent discharge rate. Infusions of these anomers (30 mg or 50 mg dissolved in 10 ml glucose-free Ringer solution) into the portal vein in perfused liver preparations and intraportal injections of these anomers (50 mg/kg dissolved in 0.2 ml saline) in vivo partially suppressed the afferent activity. However, the effect of suppression by the beta anomer was stronger than that of the alpha anomer. Results indicate the existence of anomeric stereospecificity of D-glucose action to the hepatic "glucose sensors."


2012 ◽  
Vol 107 (1) ◽  
pp. 357-363 ◽  
Author(s):  
C. Ma ◽  
H. Nie ◽  
Q. Gu ◽  
P. Sikand ◽  
R. H. LaMotte

Native cowhage spicules, and heat-inactivated spicules containing histamine or capsaicin, evoke similar sensations of itch and nociceptive sensations in humans. In ongoing studies of the peripheral neural mechanisms of chemical itch and pain in the mouse, extracellular electrophysiological recordings were obtained, in vivo, from the cell bodies of mechanosensitive nociceptive neurons in response to spicule stimuli delivered to their cutaneous receptive fields (RFs) on the distal hindlimb. A total of 43 mechanosensitive, cutaneous, nociceptive neurons with axonal conduction velocities in the C-fiber range (C-nociceptors) were classified as CM if responsive to noxious mechanical stimuli, such as pinch, or CMH if responsive to noxious mechanical and heat stimuli (51°C, 5 s). The tips of native cowhage spicules, or heat-inactivated spicules containing histamine or capsaicin, were applied to the RF. Heat-inactivated spicules containing no chemical produced only a transient response occurring during insertion. Of the 43 mechanosensitive nociceptors recorded, 20 of the 25 CMHs responded to capsaicin, and of these, 13 also responded to cowhage and/or histamine. In contrast, none of the 18 CMs responded to any of the chemical stimuli. The time course of the mean discharge rate of CMHs was similar in response to each type of spicule and generally similar, although reaching a peak earlier, to the temporal profiles of itch and nociceptive sensations evoked by the same stimuli in humans. These findings are consistent with the hypothesis that the itch and nociceptive sensations evoked by these punctuate chemical stimuli are mediated at least in part by the activity of mechanoheat-sensitive C-nociceptors. In contrast, activity in mechanosensitive C-nociceptors that do not respond to heat or to pruritic chemicals is hypothesized as contributing to pain but not to itch.


1990 ◽  
Vol 10 (1) ◽  
pp. 143-146 ◽  
Author(s):  
James A. Yergey ◽  
Melvyn P. Heyes

Formation of eicosanoids has been implicated in the pathological changes that follow brain injuries. In the present study, we used a microdialysis probe to both induce acute penetration injury and also sample extracellular fluid concentrations of eicosanoids. Formation of prostaglandin (PG) D2, PGF2 a, and thromboxane B2 was highest in the first hour following introduction of the probe into rat striatum. In contrast, the level of PGE2 was highest during the sixth hour of collection, while 6-keto-PGF1 a remained stable throughout the sampling period. We conclude that in vivo microdialysis may be useful in the evaluation of the time course of the effects of acute penetration injury of the brain on the local production of eicosanoids.


Author(s):  
J. C. Roberts ◽  
T. P. Harrigan ◽  
E. E. Ward ◽  
D. Nicolella ◽  
L. Francis ◽  
...  

Strains and pressures in the brain are known to be influenced by rotation of the head in response to loading. This brain rotation is governed by the motion of the head, as permitted by the neck, due to loading conditions. In order to better understand the effect neck characteristics have on pressures and strains in the brain, a human head finite element model (HHFEM) was attached to two neck FEMs: a standard, well characterized Hybrid III Anthropometric Test Device neck FEM; and a high fidelity parametric probabilistic human FEM neck that has been hierarchically validated. The Hybrid III neck is well-established in automotive injury prevention studies, but is known to be much stiffer than in vivo human necks. The parametric FEM is based on CT scans and anatomic data, and the components of the model are validated against biomechanical tests at the component and system level. Both integrated head-neck models were loaded using pressure histories based on shock tube exposures. The shock tube loading applied to these head models were obtained using a computational fluid dynamics (CFD) model of the HHFEM surface in front of a 6 inch diameter shock tube. The calculated pressure-time histories were then applied to the head-neck models. The global head rotations, pressures, brain displacements, and brain strains of both head-neck models were compared for shock tube driver pressures from 517 to 862 kPa. The intracranial pressure response occurred in the first 1 to 5 msec, after blast impact, prior to a significant kinematic response, and was very similar between the two models. The global head rotations and the strains in the brain occurred at 20 to 100 msec after blast impact, and both were approximately two times higher in the model using the head parametric probabilistic neck FEM (H2PN), as compared to the model using the head Hybrid III neck FEM (H3N). It was also discovered that the H2PN exhibited an initial backward and small downward motion in the first 10 ms not seen in the H3N. The increased displacements and strains were the primary difference between the two combined models, indicating that neck constraints are a significant factor in the strains induced by blast loading to the head. Therefore neck constraints should be carefully controlled in studies of brain strain due to blast, but neck constraints are less important if pressure response is the only response parameter of primary interest.


1993 ◽  
Vol 13 (5) ◽  
pp. 889-894 ◽  
Author(s):  
Franz Prielmeier ◽  
Klaus-Dietmar Merboldt ◽  
Wolfgang Hänicke ◽  
Jens Frahm

Transient alterations in brain oxygenation during 60-s periods of anoxia were visualized at high spatial resolution (voxel size ≤ 0.15 μl) with the use of serial long echo time FLASH (fast low-angle shot) magnetic resonance images (measuring time ≥ 6 s) of halothaneanesthetized rats in vivo. Difference images from normoxia and anoxia exploit the signal decrease associated with increased levels of paramagnetic deoxyhemoglobin in the arterial and venous blood pool. Insights into the spatial heterogeneity of oxygen deprivation are complemented by physiologic information from the time course of pertinent signal changes in different regions of the brain.


2019 ◽  
Author(s):  
Andrew Garfoot ◽  
Gary Wilson ◽  
Joshua Coon ◽  
Laura Knoll

Abstract Background : The protozoan pathogen Toxoplasma gondii has the unique ability to develop a chronic infection in the brain of its host by transitioning from the fast growing tachyzoite morphology to latent bradyzoite morphology. A hallmark of the bradyzoite is the development of neuronal cysts that are resilient against host immune response and current therapeutics. The bradyzoite parasites within the cyst have a carbohydrate and protein-rich wall and a slow-replication cycle, allowing them to remain hidden from the host. The intracellular, encysted lifestyle of T. gondii has made them recalcitrant to molecular analysis in vivo . Results : Here, we detail the results from transcriptional and proteomic analyses of bradyzoite-enriched fractions isolated from mouse brains infected with T. gondii over a time course of 21 to 150 days. The enrichment procedure afforded consistent identification of over 2,000 parasitic peptides from the mixed-organism sample, representing 366 T. gondii proteins at 28, 90, and 120 day timepoints. Deep sequencing of transcripts expressed during these three timepoints revealed that a subpopulation of genes that are transcriptionally expressed at a high level. Approximately one-third of these transcripts are more enriched during bradyzoite conditions compared to tachyzoites and approximately half are expressed at similar levels during each phase. The T. gondii transcript which increased the most over the course of chronic infection, sporoAMA1, shows stage specific isoform expression of the gene. Conclusions : We have expanded the transcriptional profile of in vivo bradyzoites to 120 days post-infection and provided the first in vivo proteomic profile of T. gondii bradyzoites. The RNA sequencing depth of in vivo bradyzoite T. gondii was over 250-fold greater than previous reports and allowed us to identify low level transcripts and a novel bradyzoite-specific isoform of sporoAMA1.


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