Dual Orexin Receptor Antagonist Attenuates Increases in IOP, ICP, and Translaminar Pressure Difference After Stimulation of the Hypothalamus in Rats.

PURPOSE: Intraocular pressure (IOP) remains the only modifiable risk factor for glaucoma progression. Our previous discovery that stimulation of nuclei within the hypothalamus can modulate IOP, intracranial pressure (ICP), and translaminar pressure difference (TLPD) fluctuations led us to investigate this pathway further. Our purpose was to determine the role of orexin neurons, primarily located in the dorsomedial hypothalamus (DMH) and perifornical (PeF) regions of the hypothalamus, in modulating these pressures. METHODS: Sprague Dawley rats were pretreated systemically with a dual orexin receptor antagonist (DORA-12) at 30 mg/Kg (n = 8), 10 mg/Kg (n = 8), or vehicle control (n = 8). The IOP, ICP, heart rate (HR), and mean arterial pressure (MAP) were recorded prior to and following excitation of the DMH/PeF using microinjection of the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline methiodide (BMI). RESULTS: Administration of the DORA at 30 mg/Kg significantly attenuated peak IOP by 5.2 ± 3.6 mm Hg (P = 0.007). During the peak response period (8-40 minutes), the area under the curve (AUC) for the 30 mg/Kg DORA cohort was significantly lower than the control cohort during the same period (P = 0.04). IOP responses for peak AUC versus DORA dose, from 0 to 30 mg/Kg, were linear (R2 = 0.18, P = 0.04). The ICP responses during the peak response period (4-16 minutes) versus DORA dose were also linear (R2 = 0.24, P = 0.014). Pretreatment with DORA significantly decreased AUC for the TLPD following stimulation of the DMH/PeF (10 mg/kg, P = 0.045 and 30 mg/kg, P = 0.015). CONCLUSIONS: DORAs have the potential to attenuate asynchronous changes in IOP and in ICP and to lessen the extent of TLPDs that may result from central nervous system (CNS) activation.

Systemic Hyperthermia in Traumatic Brain Injury-Relation to Intracranial Pressure Dynamics, Cerebral Energy Metabolism, and Clinical Outcome.

BACKGROUND: Systemic hyperthermia is common after traumatic brain injury (TBI) and may induce secondary brain injury, although the pathophysiology is not fully understood. In this study, our aim was to determine the incidence and temporal course of hyperthermia after TBI and its relation to intracranial pressure dynamics, cerebral metabolism, and clinical outcomes. MATERIALS AND METHODS: This retrospective study included 115 TBI patients. Data from systemic physiology (body temperature, blood pressure, and arterial glucose), intracranial pressure dynamics (intracranial pressure, cerebral perfusion pressure, compliance, and pressure reactivity), and cerebral microdialysis (glucose, pyruvate, lactate, glycerol, glutamate, and urea) were analyzed during the first 10 days after injury. RESULTS: Overall, 6% of patients did not have hyperthermia (T>38°C) during the first 10 days after injury, whereas 20% had hyperthermia for >50% of the time. Hyperthermia increased from 21% (±27%) of monitoring time on day 1 to 36% (±29%) on days 6 to 10 after injury. In univariate analyses, higher body temperature was not associated with higher intracranial pressure nor lower cerebral perfusion pressure, but was associated with lower cerebral glucose concentration (P=0.001) and higher percentage of lactate-pyruvate ratio>25 (P=0.02) on days 6 to 10 after injury. Higher body temperature and lower arterial glucose concentration were associated with lower cerebral glucose in a multiple linear regression analysis (P=0.02 for both). There was no association between hyperthermia and worse clinical outcomes. CONCLUSION: Hyperthermia was most common between days 6 and 10 following TBI, and associated with disturbances in cerebral energy metabolism but not worse clinical outcome.

Hydrogen gas inhalation improves delayed brain injury by alleviating early brain injury after experimental subarachnoid hemorrhage.

Molecular hydrogen (H2) protect neurons against reactive oxygen species and ameliorates early brain injury (EBI) after subarachnoid hemorrhage (SAH). This study investigated the effect of H2 on delayed brain injury (DBI) using the rat SAH + unilateral common carotid artery occlusion (UCCAO) model with the endovascular perforation method. 1.3% H2 gas (1.3% hydrogen premixed with 30% oxygen and balanced nitrogen) inhalation was performed on days 0 and 1, starting from anesthesia induction and continuing for 2 h on day 0, and starting from anesthesia induction and continuing for 30 min on day 1. EBI was assessed on the basis of brain edema, expression of S100 calcium-binding protein B (S100B), and phosphorylation of C-Jun N-terminal kinase on day 2, and neurological deficits on day 3. Reactive astrogliosis and severity of cerebral vasospasm (CV) were assessed on days 3 and 7. DBI was assessed on the basis of neurological deficits and neuronal cell death on day 7. EBI, reactive astrogliosis, and DBI were ameliorated in the H2 group compared with the control group. CV showed no significant improvement between the control and H2 groups. This study demonstrated that H2 gas inhalation ameliorated DBI by reducing EBI without improving CV in the rat SAH + UCCAO model.

A Comparison of Hypertonic Saline and Mannitol on Intraoperative Brain Relaxation in Patients with Raised Intracranial Pressure during Supratentorial Tumors Resection: A Randomized Control Trial.

INTRODUCTION: Hyperosmotic agents are used to decrease intracranial pressure (ICP). We aim to compare the effect of euvolemic solutions of 3% hypertonic saline (HTS) and 20% mannitol on intraoperative brain relaxation in patients with clinical or radiological evidence of raised ICP undergoing surgery for supratentorial tumors. MATERIALS AND METHODS: A.prospective double-blind study was conducted on 30 patients randomized into two equal groups. Each patient was administered 5 ml/kg of either 20% mannitol or 3% HTS over 15 minutes (min) after skin incision. Hemodynamic data, brain relaxation and serum electrolyte levels were recorded. RESULTS: Intraoperative brain relaxation was comparable between the two groups. There was a statistically significant difference in the mean arterial pressures (MAPs) between the two groups after one minutes (min) with a greater degree of decrease in blood pressure recorded in the mannitol group (P = 0.041). MAP with mannitol was significantly lower than the preinduction value after 75 min of administration of drug (P = 0.003). Urine output was significantly higher in the mannitol group (P = 0.00). Administration of HTS was associated with a transient increase in serum sodium concentrations, which was statistically significant but returned to normal within 48 h (P < 0.001). CONCLUSIONS: Both mannitol and HTS provided adequate intraoperative brain relaxation. On the contrary, there was no statistically significant fall in blood pressure with HTS. Thus, we advocate the use of HTS over mannitol as it maintains better hemodynamic stability.

The role of intracranial pressure in glaucoma and therapeutic implications.

Despite glaucoma being the second leading cause of blindness globally, its pathogenesis remains incompletely understood. Although intraocular pressure (IOP) contributes to glaucoma, and reducing IOP slows progress of the disease, some patients progress despite normal IOP (NTG). Glaucomatous damage causes characteristic cupping of the optic nerve where it passes through the lamina cribrosa. There is evidence that cerebrospinal fluid (CSF) within the optic nerve sheath has a different composition from CSF surrounding the brain. Furthermore, fluctuations in CSF flow into the optic nerve sheath may be reduced by trabeculae within the sheath, and on standing intracranial pressure (ICP) within the sheath is stabilised at around 3 mmHg due to orbital pressure. Blood pressure has been linked both to glaucoma and ICP. These facts have led some to conclude that ICP does not play a role in glaucoma. However, according to stress formulae and Laplace's Law, stress within the lamina cribrosa is dependent on the forces on either side of it, (IOP and ICP), and its thickness. On lying flat at night, ICP between the brain and optic nerve sheath should equalise. Most evidence suggests ICP is lower in glaucoma than in control groups, and that the lamina cribrosa is thinner and more posteriorly displaced in glaucoma. Subjects who have had ICP reduced have developed signs of glaucoma. This review finds most evidence supports a role for low ICP in the pathogenesis of glaucoma. Caffeine, theophylline and vitamin A may increase ICP, and could be new candidates for an oral treatment.

A Prospective Observational Feasibility Study of Jugular Bulb Microdialysis in Subarachnoid Hemorrhage.

BACKGROUND: Cerebral metabolic perturbations are common in aneurysmal subarachnoid hemorrhage (aSAH). Monitoring cerebral metabolism with intracerebral microdialysis (CMD) allows early detection of secondary injury and may guide decisions on neurocritical care interventions, affecting outcome. However, CMD is a regional measuring technique that is influenced by proximity to focal lesions. Continuous microdialysis of the cerebral venous drainage may provide information on global cerebral metabolism relevant for the care of aSAH patients. This observational study aimed to explore the feasibility of jugular bulb microdialysis (JBMD) in aSAH and describe the output characteristics in relation to conventional multimodal monitoring. METHODS: Patients with severe aSAH were included at admission or after in-house deterioration when local clinical guidelines prompted extended multimodal monitoring. Non-dominant frontal CMD, intracranial pressure (ICP), partial brain tissue oxygenation pressure (PbtO2), and cerebral perfusion pressure (CPP) were recorded every hour. The dominant jugular vein was accessed by retrograde insertion of a microdialysis catheter with the tip placed in the jugular bulb under ultrasound guidance. Glucose, lactate, pyruvate, lactate/pyruvate ratio, glycerol, and glutamate were studied for correlation to intracranial measurements. Modified Rankin scale was assessed at 6 months. RESULTS: Twelve adult aSAH patients were monitored during a mean 4.2 ± 2.6 days yielding 22,041 data points for analysis. No complications related to JBMD were observed. Moderate or strong significant monotonic CMD-to-JBMD correlations were observed most often for glucose (7 patients), followed by lactate (5 patients), and pyruvate, glycerol, and glutamate (3 patients). Moderate correlation for lactate/pyruvate ratio was only seen in one patient. Analysis of critical periods defined by ICP > 20, CPP < 65, or PbtO2 < 15 revealed a tendency toward stronger CMD-to-JBMD associations in patients with many or long critical periods. Possible time lags between CMD and JBMD measurements were only identified in 6 out of 60 patient variables. With the exception of pyruvate, a dichotomized outcome was associated with similar metabolite patterns in JBMD and CMD. A nonsignificant tendency toward greater differences between outcome groups was seen in JBMD. CONCLUSIONS: Continuous microdialysis monitoring of the cerebral drainage in the jugular bulb is feasible and safe. JBMD-to-CMD correlation is influenced by the type of metabolite measured, with glucose and lactate displaying the strongest associations. JBMD lactate correlated more often than CMD lactate to CPP, implying utility for detection of global cerebral metabolic perturbations. Studies comparing JBMD to other global measures of cerebral metabolism, e.g., PET CT or Xenon CT, are warranted.

Optic disc cupping characteristics of normal pressure hydrocephalus patients with normal-tension glaucoma.

We examined the potential association of idiopathic normal pressure hydrocephalus (iNPH) with the generation of normal-tension glaucoma (NTG), to explore possible relationships between intracranial pressure (ICP) and the presence of glaucoma, and to compare disc morphology of NTG patients with or without iNPH. We investigated 20 iNPH patients, examined the prevalence of glaucoma, and compared the optic discs of NTG patients with iNPH (n = 11) and age-matched NTG patients without iNPH (n = 16). All data were collected prior to the treatment of iNPH, to eliminate the possibility that the treatment may have contributed to the progression of NTG. The diagnoses of NTG were made using visual field data, intraocular pressure measurements, fundoscopy, and optical coherence tomography (OCT). Using OCT, the optic nerve disc depth was also measured. The ICP was higher in the iNPH with NTG compared to iNPH without NTG (p = 0.0425), and the cupping depths of the discs of NTG patients with iNPH were significantly shallower compared with those of NTG patients without iNPH (p = 0.0097). Based on the difference in cupping depth, NTG patients with iNPH may have a different morphology from typical glaucoma patients, which could in turn reflect a different pathogenesis compared to NTG patients without iNPH.

Refining non-invasive techniques to measure intracranial pressure: comparing evoked and spontaneous tympanic membrane displacements.

OBJECTIVE: Tympanic membrane displacements (TMDs) are used to non-invasively gauge inner-ear fluid pressure. Inner-ear fluid pressure equalizes with intracranial pressure (ICP) via the cochlear aqueduct and therefore TMDs can indirectly evaluate ICP. We studied the relationship between two TMD modalities, evoked and spontaneous. Evoked TMD is a reflex response to an auditory stimulus and the established stapes-footplate mechanism explains how evoked TMDs change with ICP. Spontaneous TMD refers to a pulsatile TMD waveform expressed in the form of pulse amplitudes (TMD-PAs), the origins of which are poorly understood. We investigated whether both modalities respond similarly to an ICP change, suggesting a common mechanism. APPROACH: ICP was manipulated in 20 healthy volunteers by a postural change from sitting (lower ICP) to supine (higher ICP). Differences between paired sitting and supine TMD results generated ΔEvoked and ΔSpontaneous values. MAIN RESULTS: Evoked TMDs became more inward on lying supine while spontaneous TMDs became more outward. There was no evidence of a correlation between ΔEvoked and ΔSpontaneous (Right ears: r = -0.38, p = 0.10, 95% CI -0.75 to 0.21; Left ears: r = 0.34, p = 0.16, 95% CI -0.17 to 0.75). SIGNIFICANCE: This suggests the stapes-footplate mechanism is not the primary mechanism explaining how spontaneous TMDs respond to changing ICP.

Effect of Local Ropivacaine on Hemodynamic Responses in Craniotomy Patients.

BACKGROUND: Increased intracranial pressure (ICP) with hemodynamic is of major concern to anesthesiologists and surgeons in craniotomy surgery. Thus, the management of hemodynamic stability is essential in neuro-anesthesia. This study was performed to investigate the effect of local infiltration of 0.5% ropivacaine on hemodynamic responses in craniotomy patients. MATERIAL AND METHODS: 64 ASA class I -II patients, scheduled for elective craniotomies, were enrolled in this prospective randomized double blind placebo controlled study. These patients were randomly divided into the ropivacaine group, who were administered with 0.5% ropivacaine (n = 32), and the placebo group administered with 0.9% normal saline (NaCl) (n = 32). Anesthesia was induced with 3 µg/kg fentanyl, 5 mg/kg thiopental and 0.5 mg/kg atracurium, and was maintained with isoflurane (0.8-1 = MAC) in 50% N2O, 1 mg/kg /30 minutes, 40% oxygen and 0.05 mg/kg /hour fentanyl. Five minutes prior to surgery, 10 mL of 0.5% ropivacaine was injected in the line of skin incision in the ropivacaine group, while 10 mL of normal saline was injected in placebo group. Thereafter, the systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressures (MABP), and heart rate (HR) were measured before infiltration into the incision area, 30 seconds, 3 minutes, 5, 10, and 30 minutes after infiltration into the scalp. For higher BP and HR, an adjunct 0.5 mcg/kg of fentanyl was prescribed and administered. RESULTS: A significant difference was observed for SBP, DBP, MABP and HR, between the two groups at different times during craniotomy (p < 0.05). A significant decrease was observed for SBP, DBP, MABP and HR during craniotomy in 0.5% ropivacaine group as compared with placebo group (p < 0.05). CONCLUSION: Local anesthetic of 0.05% ropivacaine scalp infiltration is effective in clinical usage of regional anesthesia for producing good quality anesthesia, it seems to be a significant choice for management of optimal hemodynamic profile, providing a better hemodynamic stability during craniotomy.

[Glibenclamide as a promising agent for prevention and treatment of cerebral edema]. / Glibenklamid - perspektivnoe sredstvo profilaktiki i lecheniia oteka golovnogo mozga.

The article presents a review of the literature on the use of a fundamentally new technique for prevention and treatment of cerebral edema. A drug glibenclamide, which is used to treat type 2 diabetes mellitus, is able to reduce cerebral edema and neuronal damage as evidenced by the results of preclinical trials in rodents and the first results of drug application in patients. The article describes the mechanism of glibenclamide action and discusses the potential for its application.

Phase I randomized clinical trial of N-acetylcysteine in combination with an adjuvant probenecid for treatment of severe traumatic brain injury in children.

BACKGROUND: There are no therapies shown to improve outcome after severe traumatic brain injury (TBI) in humans, a leading cause of morbidity and mortality. We sought to verify brain exposure of the systemically administered antioxidant N-acetylcysteine (NAC) and the synergistic adjuvant probenecid, and identify adverse effects of this drug combination after severe TBI in children. METHODS: IRB-approved, randomized, double-blind, placebo controlled Phase I study in children 2 to 18 years-of-age admitted to a Pediatric Intensive Care Unit after severe TBI (Glasgow Coma Scale [GCS] score ≤8) requiring an externalized ventricular drain for measurement of intracranial pressure (ICP). Patients were recruited from November 2011-August 2013. Fourteen patients (n = 7/group) were randomly assigned after obtaining informed consent to receive probenecid (25 mg/kg load, then 10 mg/kg/dose q6h×11 doses) and NAC (140 mg/kg load, then 70 mg/kg/dose q4h×17 doses), or placebos via naso/orogastric tube. Serum and CSF samples were drawn pre-bolus and 1-96 h after randomization and drug concentrations were measured via UPLC-MS/MS. Glasgow Outcome Scale (GOS) score was assessed at 3 months. RESULTS: There were no adverse events attributable to drug treatment. One patient in the placebo group was withdrawn due to adverse effects. In the treatment group, NAC concentrations ranged from 16,977.3±2,212.3 to 16,786.1±3,285.3 in serum and from 269.3±113.0 to 467.9±262.7 ng/mL in CSF, at 24 to 72 h post-bolus, respectively; and probenecid concentrations ranged from 75.4.3±10.0 to 52.9±25.8 in serum and 5.4±1.0 to 4.6±2.1 µg/mL in CSF, at 24 to 72 h post-bolus, respectively (mean±SEM). Temperature, mean arterial pressure, ICP, use of ICP-directed therapies, surveillance serum brain injury biomarkers, and GOS at 3 months were not different between groups. CONCLUSIONS: Treatment resulted in detectable concentrations of NAC and probenecid in CSF and was not associated with undesirable effects after TBI in children. TRIAL REGISTRATION: ClinicalTrials.gov NCT01322009.

Jugular and Portal Vein Volume, Middle Cerebral Vein Velocity, and Intracranial Pressure in Dry Immersion.

BACKGROUND: The objective was to determine if short term exposure to dry immersion (DI) results in a cephalic fluid shift similar to what has been observed with spaceflight. METHODS: Data were collected from 10 individuals at rest and during the first 2 h of dry immersion. Jugular vein (JV), portal vein (PV), and thyroid volume were measured using 3D echography. Middle cerebral vein velocity (MCVv) was determined using transcranial Doppler ultrasound. The cochlear response to audio stimulation was used to derive an estimate of intracranial pressure (dICP). RESULTS: After 2 h of DI, there was a significant increase (mean ± SD) in JV (2.21 ± 1.10 mL), PV (1.05 ± 0.48 mL), and thyroid (0.428 ± 0.313 mL) volume. MCVv was also significantly increased with DI (3.90 ± 5.03 cm · s-1). There was no change in dICP with DI in part due to large individual variability. The range of dICP changes appeared to be related to MCVv, with participants with the largest increase in MCVv also showing increased dICP. DISCUSSION: The results suggest that DI induces a significant cephalic fluid shift similar to what is observed with spaceflight. The increased thyroid volume suggests that cerebral tissue may also be subjected to similar fluid filtration, with implications for changes in intracranial pressure. However, despite all participants having an increase in JV and thyroid volume, only half showed an increase in dICP, suggesting that increased venous pooling alone is not sufficient to cause increased intracranial pressure.Arbeille P, Avan P, Treffel L, Zuj K, Normand H, Denise P. Jugular and portal vein volume, middle cerebral vein velocity, and intracranial pressure in dry immersion. Aerosp Med Hum Perform. 2017; 88(5):457-462.

Methylprednisolone modulates intracranial pressure in the brain cellular edema induced by water intoxication.

Continuous monitoring of the intracranial pressure (ICP) detects impending intracranial hypertension resulting from the impaired intracranial volume homeostasis, when expanding volume generates pressure increase. In this study, cellular brain edema (CE) was induced in rats by water intoxication (WI). Methylprednisolone (MP) was administered intraperitoneally (i.p.) before the start of CE induction, during the induction and after the induction. ICP was monitored for 60 min within 20 h after the completion of the CE induction by fibreoptic pressure transmitter. In rats with induced CE, ICP was increased (Mean+/-SEM: 14.25+/-2.12) as well as in rats with MP administration before the start of CE induction (10.55+/-1.27). In control rats without CE induction (4.62+/-0.24) as well as in rats with MP applied during CE induction (5.52+/-1.32) and in rats with MP applied after the end of CE induction (6.23+/-0.73) ICP was normal. In the last two groups of rats, though the CE was induced, intracranial volume homeostasis was not impaired, intracranial volume as well as ICP were not increased. It is possible to conclude that methylprednisolone significantly influenced intracranial homeostasis and thus also the ICP values in the model of cellular brain edema.

Craniocervical manual lymphatic drainage and its impact on intracranial pressure - a pilot study.

BACKGROUND AND PURPOSE: Theoretical considerations and the results of animal studies indicate that manual lymphatic drainage (MLD) might have an impact on intracranial pressure (ICP). There is a lack of clinically qualitative investigations on patients with severe cerebral diseases. METHODS: Between April 2013 and January 2015 a prospective observational study was performed on patients who were undergoing intracranial pressure measurement and treatment with MLD. ICP, cerebral perfusion pressure, mean arterial pressure (MAP), heart rate and oxygen saturation were recorded continuously 15 min before the procedure, during MLD (22 min) and for 15 min after the procedure. For analysis the data treatment units were divided into two groups: patients with a mean baseline ICP <15 mmHg (group 1) and patients with a mean ICP ≥15 mmHg before MLD (group 2). RESULTS: A total of 133 treatment units (61 patients) were analysed (group 1 n = 99; group 2 n = 34). The mean baseline ICP was 10.4 mmHg overall, and 8.3 mmHg and 18.6 mmHg respectively in group 1 and group 2; ICP significantly decreased during therapy with MLD and this persisted during the follow-up period in group 2. MAP did not show any significant differences between the different periods. CONCLUSIONS: Our data showed a significant reduction of ICP during therapy with craniocervical MLD in patients with severe cerebral diseases.

The interaction between intracranial pressure, intraocular pressure and lamina cribrosal compression in glaucoma.

This review examines some of the biomechanical consequences associated with the opposing intraocular and intracranial forces. These forces compress the lamina cribrosa and are a potential source of glaucomatous pathology. A difference between them creates a displacement force on the lamina cribrosa. Increasing intraocular pressure and/or decreasing intracranial pressure will increase the trans-lamina cribrosa pressure difference and the risk of its posterior displacement, canal expansion and the formation of pathological cupping. Both intraocular pressure and intracranial pressure can be elevated during a Valsalva manoeuvre with associated increases in both anterior and posterior lamina cribrosa loading as well as its compression. Any resulting thinning of or damage to the lamina cribrosa and/or retinal ganglion cell axons and/or astrocyte and glial cells attached to the matrix of the lamina cribrosa and/or reduction in blood flow to the lamina cribrosa may contribute to glaucomatous neuropathy. Thinning of the lamina cribrosa reduces its stiffness and increases the risk of its posterior displacement. Optic nerve head posterior displacement warrants medical or surgical lowering of intraocular pressure; however, compared to intraocular pressure, the trans-lamina cribrosa pressure difference may be more important in pressure-related pathology of the optic nerve head region. Similarly important could be increased compression loading of the lamina cribrosa. Reducing participation in activities which elevate intraocular and intracranial pressure will decrease lamina cribrosa compression exposure and may contribute to glaucoma management and may have prognostic significance for glaucoma suspects.

Definition, evaluation, and management of brain relaxation during craniotomy.

The term 'brain relaxation' is routinely used to describe the size and firmness of the brain tissue during craniotomy. The status of brain relaxation is an important aspect of neuroanaesthesia practice and is relevant to the operating conditions, retraction injury, and likely patient outcomes. Brain relaxation is determined by the relationship between the volume of the intracranial contents and the capacity of the intracranial space (i.e. a content-space relationship). It is a concept related to, but distinct from, intracranial pressure. The evaluation of brain relaxation should be standardized to facilitate clinical communication and research collaboration. Both advantageous and disadvantageous effects of the various interventions for brain relaxation should be taken into account in patient care. The outcomes that matter the most to patients should be emphasized in defining, evaluating, and managing brain relaxation. To date, brain relaxation has not been reviewed specifically, and the aim of this manuscript is to discuss the current approaches to the definition, evaluation, and management of brain relaxation, knowledge gaps, and targets for future research.

Erectogenic and Aphrodisiac Property of Moringa oleifera: Involvement of Soluble Epoxide Hydrolase Enzyme.

Soluble epoxide hydrolase (sEH) inhibitors have been reported to improve penile erection; therefore, sEH could be useful for management of erectile dysfunction. Methanolic and aqueous extracts of 30 Indian medicinal plants were screened for their sEH inhibition potential. Fifteen extracts showed >50% inhibition when screened at 50 µg/mL in sEH inhibition assay. Methanolic extract of Moringa oleifera Lam. (Moringaceae) seeds (MEMO) was most potent with IC50 1.7 ± 0.1 µg/mL and was selected for in vitro studies on isolated rat corpus cavernosum smooth muscle and in vivo sexual behaviour studies on healthy and diabetic rats. Rats were divided into five groups, each containing six animals and treated orally with either water, vehicle (1% Tween-20), MEMO (45 and 90 mg/kg/day for 21 days), and standard drug, sildenafil (5 mg/kg/day for 7 days). An equal number of female rats were used, and the effect of MEMO and sildenafil was compared with that of vehicle. MEMO significantly relaxed isolated rat corpus cavernosum smooth muscle at 0.1-100 µg/mL in vitro and significantly increased (p < 0.05) sexual activity, intracavernous pressure/mean arterial pressure in normal and diabetic rats. The increase in erectile function of rats by MEMO could be because of its sEH inhibitory activity. Copyright © 2016 John Wiley & Sons, Ltd.

The effect of increased intracranial pressure on vestibular evoked myogenic potentials in superior canal dehiscence syndrome.

OBJECTIVE: To determine if vestibular evoked myogenic potential (VEMP) responses change during inversion in patients with superior canal dehiscence syndrome (SCDS) compared to controls. METHODS: Sixteen subjects with SCDS (mean: 43, range 30-57 years) and 15 age-matched, healthy subjects (mean: 41, range 22-57 years) completed cervical VEMP (cVEMP) in response to air conduction click stimuli and ocular VEMP (oVEMP) in response to air conduction 500 Hz tone burst stimuli and midline tap stimulation. All VEMP testing was completed in semi-recumbent and inverted conditions. RESULTS: SCDS ears demonstrated significantly larger oVEMP peak-to-peak amplitudes in comparison to normal ears in semi-recumbency. While corrected cVEMP peak-to-peak amplitudes were larger in SCDS ears; this did not reach significance in our sample. Overall, there was not a differential change in o- or cVEMP amplitude with inversion between SCDS and normal subjects. CONCLUSIONS: Postural-induced changes in o- and cVEMP responses were measured in the steady state regardless of whether the labyrinth was intact or dehiscent. SIGNIFICANCE: VEMP responses are blunted during inversion. Although steady-state measurements of VEMPs during inversion do not increase diagnostic accuracy for SCDS, the findings suggest that inversion may provide more general insights into the equilibration of pressures between intracranial and intralabyrinthine fluids.