Accommodation Reflex Research Articles

Modern methods to assess accommodation reflex (literature review)

Background. Determination of reflex accommodation indicators is of particular interest, both from clinical and scientific points of view. However, the heterogeneity of methods and approaches for evaluation of results obtained makes it necessary to compare and confront them in details.Purpose: to summarize and systematize the literature-based data of modern accommodation measurement methods.Methods. The analysis of domestic monographs was carried out. The domestic and foreign articles on eLibrary and PubMed within the last 20 years were analyzed. The articles with an incomplete selection criteria and statistically unreliable results (p < 0.05) were excluded.Results. Though the measurements of reflex accommodation indicators by subjective methods are consistent with each other, they are overestimated compared to the results of objective studies. Among the objective methods, special attention should be paid to the open-field autorefractometers as they level possible instrumental accommodation that is typical for the closed-field autorefractometers. Regarding this, it is necessary to clarify the methods used in the studies of this direction. By taking into account the indicators of reflex accommodation for assessing pathological conditions and treatment results, it is necessary to consider relative (i. e., comparative) measurement values but not absolute ones.Conclusion. The analysis of literature sources showed that the modern approaches of reflex accommodation study were very different. The methods discussed in this review are suitable for both clinical and scientific practice application. However, a mandatory reference to the method used is required for a correct assessment of results.

A single-cell transcriptomic atlas of the human ciliary body

The ciliary body critically contributes to the ocular physiology with multiple responsibilities in the production of aqueous humor, vision accommodation and intraocular immunity. Comparatively little work, however, has revealed the single-cell molecular taxonomy of the human ciliary body required for studying these functionalities. In this study, we report a comprehensive atlas of the cellular and molecular components of human ciliary body as well as their interactions using single-cell RNA sequencing (scRNAseq). Cluster analysis of the transcriptome of 14,563 individual ciliary cells from the eyes of 3 human donors identified 14 distinct cell types, including the ciliary epithelium, smooth muscle, vascular endothelial cell, immune cell and other stromal cell populations. Cell-type discriminative gene markers were also revealed. Unique gene expression patterns essential for ciliary epithelium-mediated aqueous humor inflow and ciliary smooth muscle contractility were identified. Importantly, we discovered the transitional states that probably contribute to the transition of ciliary macrophage into retina microglia and verified no lymphatics in the ciliary body. Moreover, the utilization of CellPhoneDB allowed us to systemically infer cell–cell interactions among diverse ciliary cells including those that potentially participate in the pathogenesis of glaucoma and uveitis. Altogether, these new findings provide insights into the regulation of intraocular pressure, accommodation reflex and immune homeostasis under physiological and pathological conditions.

Binocular Function in Different Gaze Positions.

PurposeTo evaluate varied aspects of binocular function in multiple gaze positions.MethodsIn 2018, this cross-sectional study was conducted on 21 participants (male = 11) with an age range of 19–25 years. Having emmetropia and 10/10 visual acuity in both eyes were conditions of the inclusion criteria for the cross-sectional study. The following aspects of binocular function including amplitude of accommodation (AA), near point of convergence, near phoria, and monocular accommodative facility were evaluated in five gazes (primary, upward, downward, left, and right) for all subjects.ResultsNear point of convergence values showed significant differences in all gaze positions (P 0.001). The lowest near point of convergence value was seen in the primary gaze (2.69 cm) and the downward gaze (3.47 cm) and the highest near point of convergence value was seen in the left gaze (7.5 cm). There was also a significant difference in the amplitude of accommodation among the upward, downward, and the primary gaze (P 0.001) positions but no difference was observed among the temporal, nasal, and the primary gaze positions. There was a significant difference in near phoria between the upward gaze and the primary gaze (P = 0.008) while no significant differences were observed among the other gazes. There was no significant variance in the monocular accommodative facility among the different gaze positions (P = 0.175).ConclusionThe results of this study indicated variations that exist in the convergence and accommodation reflex functions in multiple gaze positions, which proved to be more prominent in the convergence system. Although the accommodative sufficiency evaluation was inconsistent among the multiple gaze positions, the accommodative facility evaluation was consistent in all gazes.

Assessing the Efficacy of Low-Dose Topical Atropine (0.01%) for Controlling the Progress of Myopia among School Children

Background: It is one of the most common abnormalities of human eyes and its incidence has dramatically risen in incidence in the last few decades. Myopia may lead to irreversible vision loss. A number of studies reflect on the effectiveness of low concentration atropine in controlling myopia. Atropine is used topically as a cycloplegic for the accommodation reflex and as a mydriatic for pupillary dilatation. Since myopia is leading cause of diminution of vision in early childhood, use of atropine (0.01%) in early stages can provide regression in myopic changes in eye. This study aimed to assess the change in spherical equivalent, changes in axial and keratometry values and retinal degenerative changes in cases of myopia treated with low dose atropine.
 Methodology: The enrolled cases of myopia will undergo thorough ophthalmological examination and will be randomized into intervention and control groups. All cases in intervention group will be treated with low dose atropine (0.01%) eye drops at night and will be followed up every 6 months for examination. The control group will be provided refractive spectacles and also followed up every 6 months. The data from both groups will be compared and analysed.
 Expected Results: Significant reduction in the progression of Myopia among school going children is expected with administration of 0.01% atropine eye drops.
 Conclusion: Use of atropine (0.01%) in early stages can provide regression in myopic changes in eye.

Tonic pupil secondary to varicella-zoster-virus (VZV) keratouveitis in a child

Abstract Introduction: An unusual case of tonic pupil in a 4-year-old male child secondary to Varicella-Zoster-Virus (VZV) keratouveitis is described in this case report. To the best of our knowledge, our report is the thirtieth case of tonic pupil following chickenpox infection in the literature. Patient concerns: A 4-year-old male child presented at our department in June 2019 with anisocoria and feeling generally unwell. The right pupil was noted by his mother to be larger than the left in normal, bright and dim illumination conditions. Of note, the child at the same time was suffering from chickenpox and the symptoms started approximately 4 days prior to the attendance at Accident and Emergency with a generalized vesicular rash. The mother also reported that the right eye was mildly red and uncomfortable and her son was complaining of photophobia. Diagnosis: Tonic pupil secondary to VZV keratouveitis. Interventions: Full past medical and ocular history was obtained. The patient underwent full ophthalmic examination including dilated fundoscopy. Visual acuity was recorded with Snellen Chart and Keeler chart of Minimum Angle of Resolution chart. Patient had Magnetic Resonance Imaging due to anisocoria to exclude intracranial pathology. The child was treated with intravenous Acyclovir and had a good recovery, though the anisocoria persisted. Outcomes: During the follow-ups in the Paediatric Ophthalmology Clinic, 0.125% pilocarpine test revealed profound miosis of the affected right pupil and normal response from the healthy left pupil. In addition, the range of accommodation was reduced in the affected right eye. The child was closely observed to prevent right eye amblyopia and the plan was to issue bifocals to maximize both near and distant visual acuity. Nevertheless, during close follow-up the accommodation reflex in the right eye recovered on its own and the child was eventually discharged from the clinic without executive bifocals. Conclusion: VZV keratouveitis leading to tonic pupil is a rare complication. The proposed pathophysiological mechanism is retrograde dissemination of the infection through the parasympathetic nerve fibers from the iris via the inferior branch of the third nerve to the ciliary ganglion. Our case emphasizes the potential amblyogenic consequences of tonic pupil.

The gastrointestinal tract in hunger and satiety signalling.

BackgroundDifferent peripheral pathways are implicated in the regulation of the food ingestion‐digestion cycle.MethodsNarrative review on gastrointestinal mechanisms involved in satiety and hunger signalling.ResultsCombined mechano‐ and chemoreceptors, peripherally released peptide hormones and neural pathways provide feedback to the brain to determine sensations of hunger (increase energy intake) or satiation (cessation of energy intake) and regulate the human metabolism. The gastric accommodation reflex, which consists of a transient relaxation of the proximal stomach during food intake, has been identified as a major determinant of meal volume, through activation of tension‐sensitive gastric mechanoreceptors. Motilin, whose release is the trigger of gastric Phase 3, has been identified as the major determinant of return of hunger after a meal. In addition, the release of several peptide hormones such as glucagon‐like peptide 1 (GLP‐1), cholecystokinin as well as motilin and ghrelin contributes to gut‐brain signalling with relevance to control of hunger and satiety. A number of nutrients, such as bitter tastants, as well as pharmacological agents, such as endocannabinoid receptor antagonists and GLP‐1 analogues act on these pathways to influence hunger, satiation and food intake.ConclusionGastrointestinal mechanisms such as gastric accommodation and motilin release are key determinants of satiety and hunger.

Brainstem Neuronal Circuitries Controlling Gastric Tonic and Phasic Contractions: A Review.

This review is on how current knowledge of brainstem control of gastric mechanical function unfolded over nearly four decades from the perspective of our research group. It describes data from a multitude of different types of studies involving retrograde neuronal tracing, microinjection of drugs, whole-cell recordings from rodent brain slices, receptive relaxation reflex, accommodation reflex, c-Fos experiments, immunohistochemical methods, electron microscopy, transgenic mice, optogenetics, and GABAergic signaling. Data obtained indicate the following: (1) nucleus tractus solitarius (NTS)-dorsal motor nucleus of the vagus (DMV) noradrenergic connection is required for reflex control of the fundus; (2) second-order nitrergic neurons in the NTS are also required for reflex control of the fundus; (3) a NTS GABAergic connection is required for reflex control of the antrum; (4) a single DMV efferent pathway is involved in brainstem control of gastric mechanical function under most experimental conditions excluding the accommodation reflex. Dual-vagal effectors controlling cholinergic and non-adrenergic and non-cholinergic (NANC) input to the stomach may be part of the circuitry of this reflex. (5) GABAergic signaling within the NTS via Sst-GABA interneurons determine the basal (resting) state of gastric tone and phasic contractions. (6) For the vagal-vagal reflex to become operational, an endogenous opioid in the NTS is released and the activity of Sst-GABA interneurons is suppressed. From the data, we suggest that the CNS has the capacity to provide region-specific control over the proximal (fundus) and distal (antrum) stomach through engaging phenotypically different efferent inputs to the DMV.

SPARC: Respiratory‐Gated Transcutaneous Vagus Nerve Stimulation Modulates Gastric Function in Functional Dyspepsia

The vagus nerve plays an important role in both sensory and motor aspects of gastric physiology. Both animal and human studies suggest that accommodation reflex consists of a vagovagal reflex pathway. Thus, modulating vagal efference may be promising to increase gastric hypomotility for gastroparesis or functional dyspepsia.Transcutaneous vagus nerve stimulation (tVNS) of the auricular branch of the vagus nerve is a promising non‐invasive neuromodulatory therapy for numerous disorders. We have demonstrated that tVNS targets nucleus tractus solitarii, and medullary efferent parasympathetic (vagal) nuclei (Sclocco et al. 2019). Our group showed that neural target‐engagement can be enhanced by gating stimulation to the exhalation phase of respiration, via Respiratory‐gated Auricular Vagal Afferent Nerve Stimulation (RAVANS).In this ongoing study, we evaluate nine (9) functional dyspepsia (FD) patients with both brain fMRI and 4D cine MRI of the stomach during a test meal challenge and concurrent RAVANS or Sham tVNS, to investigate effects on gastric emptying. MRI examinations were performed immediately following ingestion of a food‐based MRI contrast test meal (470ml, pineapple‐based with high manganese content), using 4D cine MRI. Each subject was scanned 15, 65, and 80 minutes post‐meal (T0, T1, T2), while experiencing active RAVANS (300μs pulse width, 1.5s stimulation trains delivered at 100Hz in the cymba concha of the left ear) or Sham (no current) on two different visits (randomized order). Abdominal MRI images were segmented to isolate the stomach, meal and air contents (semi‐automated, based on image contrast) for each subject and post‐meal time point, and volumetric indices of gastric accommodation and emptying were calculated.In FD patients, the ratio between total gastric volume and ingested volume – a proxy for gastric accommodation – was significantly higher during RAVANS compared to Sham (RAVANS: 1.46 ± 0.45, mean ± SD; Sham: 1.18 ± 0.34; p‐val = 0.024). Furthermore, the percent reduction in meal volumes during RAVANS were significantly higher compared to Sham from T0 to T1 (RAVANS: −18.18 ± 11.70%; Sham: −10.40 ± 7.47%; p‐val = 0.032), and from T0 to T2 (RAVANS: −32.68 ± 10.56%; Sham: −24.24 ± 13.63%; p‐val = 0.047).These results support the hypothesis that RAVANS can successfully modulate gastric accommodation and emptying in FD patients. Future investigations will link fMRI response to RAVANS with gut motility to investigate the brain‐gut axis underlying tVNS‐modulated gastric physiology.Support or Funding InformationWe thank the following organizations for funding support: US National Institutes of Health (NIH), Office Of The Director (OT2‐OD023867); National Institute of Biomedical Imaging and Bioengineering (R21‐EB024701); National Center for Complementary and Integrative Health, NIH (R61‐AT009306, P01‐AT006663, R01‐AT007550); National Institute of Diabetes and Digestive and Kidney Diseases (R21‐DK116029).(a) Mosaic image of abdominal 3D MRI data with air (yellow) and meal (red) segmentations; (b) 3D reconstruction of the gastric volume; (c) 3D gastric reconstruction mapping the average displacement on the stomach surface.Figure 1

1853 Impaired Gastric Accommodation: A Key Player in Functional Dyspepsia

INTRODUCTION: Poor gastric accommodation (GA) causes inadequate relaxation of the stomach during a meal. This leads to early satiety, fullness sensation, nausea, and vomiting. Poor GA is frequently seen in functional GI disorders and often coincided with anxiety and stress. It should be considered in the absence of metabolic disorders, eating disorders, and self-induced vomiting. Poor GA is quantified by the average increase of gastric volume after a meal over 1 hour. Poor GA is thought to be caused by altered neuro-modulatory pathways that affect accommodation time after a meal. CASE DESCRIPTION/METHODS: A 53-year-old woman with history of Type II Diabetes with Hba1c: 9.4%, complicated by diabetic neuropathy was admitted for treatment of UTI and Herpes Zoster. She also complained of new onset nausea, vomiting, and early satiety for 1 week. She could tolerate only thin liquids but no solids, due to persistent emesis within 10-20 min of food ingestion. An EGD was done and ruled out gastric outlet obstruction, but revealed candida esophagitis, which was treated with Fluconazole. The patient was then started empirically on Metoclopramide for presumptive Gastroparesis in the setting of poorly controlled Diabetes. The dose was gradually titrated up without favorable response. Her therapy was then escalated to Erythromycin along with Zofran and Benadryl, with no success. The patient was unable to complete a Gastric Emptying (GE) Study twice due to emesis following radiotracer ingestion. However, images from incomplete GE studies showed rapid movement of radiotracer from the fundus to the antrum. The patient was then switched to Buspirone 5 mg 30 minutes before lunch and dinner with remarkable improvement of her symptoms in 2 days. DISCUSSION: Early redistribution of radiotracer seen on scintigraphy is suggestive of impaired accommodation and is usually associated with early satiety, dyspepsia, nausea and vomiting. Rapid clinical improvement after 5-HT1a receptor agonist therapy not only implies anxiety and stress as contributing factors in this disorder, but also the role of presynaptic inhibitory 5-HT1a receptor activation in the gastric accommodation reflex. This allows for better stomach relaxation both in fasting and postprandial states. This therapy should be considered in patients with gastroparesis-like symptoms, but rapid gastric emptying seen on scintigraphy.

Duodenal nutrient exposure contributes to enhancing gastric accommodation.

The gastric accommodation reflex consists of a relaxation which creates a reservoir for the ingested food before emptying to the duodenum occurs. The mechanisms that control gastric accommodation are not fully understood. This study aims to use intragastric pressure (IGP) measurement and pyloric balloon obstruction to determine the contribution of duodenal nutrient exposure to gastric accommodation and meal-induced satiation. Two conditions were tested in 11 healthy subjects (28.3±3.2years; 23.6±0.7kg/m2 ; four females). IGP was measured during an intragastric nutrient drink (ND) infusion at a constant rate (60mL/min) in the presence of a deflated (control) or inflated (pyloric obstruction) balloon placed into the pylorus. During the study, subjects filled out Likert scales for satiation scores and visual analogue scale for 9 epigastric symptoms (hunger, expected amount to eat, satiation, bloating, fullness, nausea, belching, gastric cramps, and pain) before and during ND infusion until maximal satiation. During pyloric obstruction, the IGP drop and the area above the IGP curve (AAC) were significantly smaller compared with the control condition (6.7±1.0mmHg vs3.6±0.8mmHg, P=.03 and 69.7±13.5mmHg×min vs 20.1±9.0mmHg×min, P=.001, respectively). Pyloric obstruction decreased nutrient tolerance compared with the control condition (787.9±73.1mL vs 970.9±79.2mL, respectively, P<.05). Pyloric obstruction increased symptoms of bloating (1.3±0.4 vs 2.6±0.6; P=.04), fullness (2.3±0.5 vs 3.6±0.3; P=.03), and nausea (0.4±0.2 vs 1.3±0.4; P=.04) compared to control. Duodenal nutrient exposure contributes to enhancing gastric accommodation. Preventing the passage of nutrients from the stomach to the duodenum inhibits gastric accommodation and increases meal-induced satiation, bloating, nausea, and fullness.

Automatic Detection of Driver Impairment Based on Pupillary Light Reflex

The main objective of this paper is to determine the feasibility of designing a driver drunkenness detection system based on the dynamic analysis of a subject’s pupillary light reflex (PLR). This involuntary reaction is widely utilized in the medical field to diagnose a variety of diseases, and in this paper, the effectiveness of such a method to reveal an impairment condition due to alcohol abuse is evaluated. The test method consists in applying a light stimulus to one eye of the subject and to capture the dynamics of constriction of both eyes; for extracting the pupil size profiles from the video sequences, a two-step methodology is described, where in the first phase, the iris/pupil search within the image is performed, and in the second stage, the image is cropped to perform pupil detection on a smaller image to improve time efficiency. The undesired pupil dynamics arising in the PLR are defined and evaluated; a spontaneous oscillation of the pupil diameter is observed in the range [0, 2] Hz and the accommodation reflex causes pupil constriction of about 10% of the iris diameter. A database of pupillary light responses is acquired on different subjects in baseline condition and after alcohol consumption, and for each one, a first-order model is identified. A set of features is introduced to compare the two populations of responses and is used to design a support vector machine classifier to discriminate between “Sober” and “Drunk” states.

Rehabilitation methods for individuals with functional vision disorders

To develop a rehabilitation system for people with functional vision disorders. The study included 56 schoolchildren with functional visual impairments aged 8-17 years, among which 7 had spasm of accommodation, and 49 - paralysis or paresis of accommodation. The examination included visometry, refractometry, ophthalmometry, measurement of the axial eye length, absolute and relative accommodation parameters, fusional reserves, as well as character of binocular vision and asthenopic complaints. The patients with spasms, pareses and paralyses of accommodation were revealed to have decreased visual acuity, absence or sharp decrease in absolute and relative accommodation, fusional reserves, and simultaneous vision. A method for treating such patients has been developed, which aims for improvement of the blood supply to the ciliary muscle, accommodation reflex, visual acuity and differential sensitivity of the retina, vergence and version accommodation tonicity, convergence and fusion ability. The treatment led to normalization of absolute and relative accommodation, and increase of fusional reserves. The character of vision became binocular, asthenopic complaints stopped. The 'anlauf' glasses allow long-term preservation of the effect of received treatment, as well as prevention of visual disturbances in eye-straining work. The complex approach to the treatment of patients with spasms, pareses and paralyses of accommodation leads to restoration of the functions of visual analyzer in fairly short time (15-20 sessions).

Abdominal distension in health and irritable bowel syndrome: The effect of bladder filling.

Abdominal distension is a common feature of irritable bowel syndrome (IBS), which is difficult to treat and can have the appearance of late pregnancy. It results from an abnormality of the normal accommodation reflex which keeps abdominal girth constant despite changes in gastrointestinal volume resulting from food ingestion or gas accumulation. We speculated that bladder filling might also trigger this abnormal reflex in IBS and this study tested this hypothesis. Eight females with IBS (aged 21-43, mean 34) were compared with seven female controls (aged 19-56, mean 31) at the same time in the menstrual cycle. Abdominal girth in response to maximum tolerated bladder filling following ingestion of 1500mls of water was measured using abdominal inductance plethysmography. Symptoms, girth change after bladder emptying, and urine volumes were also recorded. Baseline girth of patients and controls was 84.8 and 79.9cm respectively. After reaching maximum tolerated bladder filling, girth increased by a mean of 6.4 (Standard deviation (SD) 2.1) cm in patients compared with 3.5 (1.1) in controls (P=0.006), with patients having symptoms of bladder hypersensitivity. After voiding urine, girth reduced by 5.3 (3.1) and 1.9 (1.2) in patients vs controls (P=0.018), despite passing similar mean urine volumes, 789 (364)mls vs 671(286) (P=0.50). Bladder filling contributes to abdominal distension in IBS and is unrelated to urine volume suggesting that bladder stretch or hypersensitivity might trigger this response. Frequent bladder emptying may help control this intrusive problem which is very challenging to manage.

A Novel Method for Estimating Free Space 3D Point-of-Regard Using Pupillary Reflex and Line-of-Sight Convergence Points

In this paper, a novel 3D gaze estimation method for a wearable gaze tracking device is proposed. This method is based on the pupillary accommodation reflex of human vision. Firstly, a 3D gaze measurement model is built. By uniting the line-of-sight convergence point and the size of the pupil, this model can be used to measure the 3D Point-of-Regard in free space. Secondly, a gaze tracking device is described. By using four cameras and semi-transparent mirrors, the gaze tracking device can accurately extract the spatial coordinates of the pupil and eye corner of the human eye from images. Thirdly, a simple calibration process of the measuring system is proposed. This method can be sketched as follows: (1) each eye is imaged by a pair of binocular stereo cameras, and the setting of semi-transparent mirrors can support a better field of view; (2) the spatial coordinates of the pupil center and the inner corner of the eye in the images of the stereo cameras are extracted, and the pupil size is calculated with the features of the gaze estimation method; (3) the pupil size and the line-of-sight convergence point when watching the calibration target at different distances are computed, and the parameters of the gaze estimation model are determined. Fourthly, an algorithm for searching the line-of-sight convergence point is proposed, and the 3D Point-of-Regard is estimated by using the obtained line-of-sight measurement model. Three groups of experiments were conducted to prove the effectiveness of the proposed method. This approach enables people to obtain the spatial coordinates of the Point-of-Regard in free space, which has great potential in the application of wearable devices.

Gastric accommodation in healthy subjects studied by ultrasound, manometry, and impedancemetry.

Gastric accommodation to a meal may be important in the pathogenesis of upper gastrointestinal disorders, but has been difficult to investigate in a minimally invasive fashion. We studied gastric and lower esophageal physiology during food intake, combining transabdominal ultrasound, multichannel high-resolution impedance-manometry (HRIM) and a symptom questionnaire. A HRIM catheter was distally positioned at incisura angularis and 300mL saline with 75g glucose was ingested. Target variables were recorded for 30min after fluid intake. Fifteen healthy subjects' participated (11W/4M, median age 23.8y) and all accepted the meal with few symptoms. At incisura angularis maximum change in pressure from pre-intake values was -7.4mmHg after 60s (P<.0001), rising to pre-intake values within 20min. The corresponding area increased significantly from pre-intake values of 8.0cm2 to 14.1cm2 shortly after intake (P=.0012), peaked at 5min and slowly decreased towards 30min. The corresponding maximum change in stress from pre-intake pressure values was -59.2mmHg shortly after (P<.0001), reaching pre-intake values within 20min. Strain rose from 0 shortly before to 0.36 shortly after (P<.0001), peaking at 5min. At incisura angularis, fullness was positively correlated with area and to strain, while fullness, area, and stress were negatively correlated with pressure. The multimodal method enabled assessment of the gastric accommodation reflex, stress and strain in the stomach. It triggered few symptoms in healthy volunteers. We propose it to be a more physiological replacement of the barostat technique.

Optofluidic lens actuated by laser-induced solutocapillary forces

We demonstrate an adaptive liquid lens controlled by laser-induced solutocapillary forces. The liquid droplet serving as a lens is formed in a thin layer of binary liquid mixture by surface tension driven flows caused by the thermal action of laser irradiation. The shape of droplet, its aperture and the focal length are reversibly changed without hysteresis by varying the intensity of the laser beam. The focal length variation range of the droplet-lens lies in between infinity (a flat layer) to 15mm (a curved interface). The droplet-lens is capable to adjust the in-plane lateral position in response to a displacement of the laser beam. The proposed laser controlled droplet-lens will enable to develop smart liquid optical devices, which can imitate the accommodation reflex and pupillary light reflex of the eye.

Change in the Interstitial Cells of Cajal and nNOS Positive Neuronal Cells with Aging in the Stomach of F344 Rats

The gastric accommodation reflex is an important mechanism in gastric physiology. However, the aging-associated structural and functional changes in gastric relaxation have not yet been established. Thus, we evaluated the molecular changes of interstitial cell of Cajal (ICC) and neuronal nitric oxide synthase (nNOS) and the function changes in the corpus of F344 rats at different ages (6-, 31-, 74-wk and 2-yr). The proportion of the c-Kit-positive area in the submucosal border (SMB) and myenteric plexus (MP) layer was significantly lower in the older rats, as indicated by immunohistochemistry. The density of the nNOS-positive immunoreactive area also decreased with age in the SMB, circular muscle (CM), and MP. Similarly, the percent of nNOS-positive neuronal cells per total neuronal cells and the proportion of nNOS immunoreactive area of MP also decreased in aged rats. In addition, the mRNA and protein expression of c-Kit and nNOS significantly decreased with age. Expression of stem cell factor (SCF) and the pan-neuronal marker PGP 9.5 mRNA was significantly lower in the older rats than in the younger rats. Barostat studies showed no difference depending on age. Instead, the change of volume was significantly decreased by L-NG63-nitroarginine methyl ester in the 2-yr-old rats compared with the 6-wk-old rats (P = 0.003). Taken together, the quantitative and molecular nNOS changes in the stomach might play a role in the decrease of gastric accommodation with age.

Traumatic superior orbital fissure syndrome: a rare case report

Superior orbital fissure syndrome is a severe clinical entity characterized by injuries of neurovascular structures passing through the superior orbital fissure. A 38-year-old male patient admitted to outpatient clinic with left upper eyelid ptosis, ecchymosis, mydriasis, hypoesthesia in upper eyelid and frontal region, blepharoptosis, restriction of ocular movements in all directions, loss of accommodation reflex and absence of direct pupillary reflex. Three-dimensional computed tomography scans demonstrated left-sided orbital fractures resulting in obliteration of the superior orbital fissure. He underwent surgical decompression. The patient had intravenous methylprednisolone administration at preoperative and postoperative periods during hospitalization. He was discharged on the postoperative day 5. At the 9 th postoperative month, the cranial nerve functions were almost completely recovered. We consider that the decompressive surgery in conjunction with perioperative steroid therapy may be effective for the traumatic superior orbital fissure syndrome.

Hindbrain glucoprivation effects on gastric vagal reflex circuits and gastric motility in the rat are suppressed by the astrocyte inhibitor fluorocitrate.

Fasting and hypoglycemia elicit powerful gastrointestinal contractions. Whereas the relationship between utilizable nutrient and gastric motility is well recognized, the explanation of this phenomenon has remained incomplete. A relatively recent controversial report suggested that astrocytes in the dorsal hindbrain may be the principal detectors of glucoprivic stimuli. Our own studies also show that a subset of astrocytes in the solitary nucleus (NST) is activated by low glucose. It is very likely that information about glucopenia may directly impact gastric control because the hindbrain is also the location of the vago-vagal reflex circuitry regulating gastric motility. Our in vivo single unit neurophysiological recordings in intact rats show fourth ventricular application of 2-deoxyglucose (2-DG) inhibits NST neurons and activates dorsal motor nucleus (DMN) neurons involved in the gastric accommodation reflex. Additionally, as shown in earlier studies, either systemic insulin or central 2-DG causes an increase in gastric motility. These effects on motility were blocked by fourth ventricle pretreatment with the astrocyte inactivator fluorocitrate. Fluorocitrate administered alone has no effect on gastric-NST or -DMN neuron responsiveness, or on gastric motility. These results suggest that glucoprivation-induced increases in gastric motility are dependent on intact hindbrain astrocytes.

CXCL12 sensitizes vago-vagal reflex neurons in the dorsal medulla

Previous studies from our laboratory illustrated the potential for stromal cell-derived factor one [CXCL12; also referred to as SDF-1] to act on its receptor [CXCR4] within the dorsal vagal complex [DVC] of the hindbrain to suppress gastric motility (Hermann et al., 2008). While CXCR4 receptors are essential for normal brain development, they also play a critical role in the proliferation of the HIV virus and initiation of metastatic cell growth in the brain. Anorexia, nausea, and failed autonomic regulation of gastrointestinal function are significant causes of morbidity and are contributory factors in the mortality associated with these disease states. The implication of our previous study was that CXCL12 caused gastric stasis by acting on gastric reflex circuit elements in the DVC. This hindbrain complex includes vagal afferent terminations in the solitary nucleus, neurons in the solitary nucleus (NST) and visceral efferent motorneurons in the dorsal motor nucleus (DMN) that are responsible for the regulation of digestive functions from the oral cavity to the transverse colon. In the current study, in vivo single-unit neurophysiological recordings from physiologically-identified NST and DMN components of the gastric accommodation reflex show that while injection of femtomole doses of CXCL12 onto NST or DMN neurons has no effect on their basal activity, CXCL12 amplifies the effect of gastric vagal mechanosensory input to activate the NST and, in turn, inhibit DMN motor activity.