Neurogenesis and astrogenesis contribute to vestibular compensation in the neurectomized adult cat: cellular and behavioral evidence

Neurogenesis occurs in some regions of the adult mammalian brain and gives rise to neurons integrated into functional networks. In pathological or postlesional conditions, neurogenesis and astrogenesis can also occur, as demonstrated in the deafferented vestibular nuclei after unilateral vestibular neurectomy in the adult cat. Here we report that in cats infused with an antimitotic drug, cytosine-[beta]-D arabinofuranoside (AraC), the number of GAD67 and GFAP immunoreactive cells is increased, despite the total mitotic activity blockade observed in the deafferented vestibular nuclei after unilateral vestibular neurectomy. At the behavioral level, recovery of posturo-locomotor function was drastically delayed, and no alteration of the horizontal spontaneous nystagmus was observed. These cellular and behavioral results suggest that reactive neurogenesis and astrogenesis might contribute highly to vestibular compensation in the adult cat, probably by accelerating the recovery of vestibular functions

Hypnosis for acute procedural pain: a critical review

Clinical evidence for the effectiveness of hypnosis in the treatment of acute procedural pain was critically evaluated based on reports from randomized controlled clinical trials (RCTs). Results from the 29 RCTs meeting inclusion criteria suggest that hypnosis decreases pain compared to standard care and attention control groups and that it is at least as effective as comparable adjunct psychological or behavioral therapies. In addition, applying hypnosis in multiple sessions prior to the day of the procedure produced the highest percentage of significant results. Hypnosis was most effective in minor surgical procedures. However, interpretations are limited by considerable risk of bias. Further studies using minimally effective control conditions and systematic control of intervention dose and timing are required to strengthen conclusions

Confronting the opioid crisis: Practical pain management and strategies: AOA 2018 critical issues symposium

The United States is in the midst of an opioid crisis. Clinicians have been part of the problem because of overprescribing of narcotics for perioperative pain management. Clinicians need to understand the pathophysiology and science of addiction to improve perioperative management of pain for their patients. Multiple modalities for pain management exist that decrease the use of narcotics. Physical strategies, cognitive strategies, and multimodal medication can all provide improved pain relief and decrease the use of narcotics. National medical societies are developing clinical practice guidelines for pain management that incorporate multimodal strategies and multimodal medication. Changes to policy that improve provider education, access to naloxone, and treatment for addiction can decrease narcotic misuse and the risk of addiction

General anesthesia does not have persistent effects on attention in rodents

Background: Studies in animals have shown that general anesthesia can cause persistent spatial memory impairment, but the influence of anesthetics on other cognitive functions is unclear. This study tested whether exposure to general anesthesia without surgery caused a persistent deficit in attention in rodents.Methods: To evaluate whether anesthesia has persistent effects on attention, rats were randomized to three groups. Group A was exposed for 2 h to isoflurane anesthesia, and tested the following seven days for attentional deficits. Group B was used as a control and received room air before attentional testing. Since there is some evidence that a subanesthetic dose of ketamine can improve cognition and reduce disorders of attention after surgery, rats in group C were exposed to isoflurane anesthesia in combination with a ketamine injection before cognitive assessment. Attention was measured in rats using the 5-Choice Serial Reaction Time Task, for which animals were trained to respond with a nose poke on a touchscreen to a brief, unpredictable visual stimulus in one of five possible grid locations to receive a food reward. Attention was analyzed as % accuracy, % omission, and premature responses.Results: Evaluating acute attention by comparing baseline values with data from the day after intervention did not reveal any differences in attentional measurements. No significant differences were seen in % accuracy, % omission, and premature responses for the three groups tested for 7 consecutive days.Conclusion: These data in healthy rodents suggest that general anesthesia without surgery has no persistent effect on attention and the addition of ketamine does not alter the outcome

Glucocorticoid-endocannabinoid interaction in cardiac surgical patients: relationship to early cognitive dysfunction and late depression

Background: Endocannabinoids (ECs) are rapidly acting immune-modulatory lipid-signaling molecules that are important for adaptation to stressful and aversive situations. They are known to interact with glucocorticoids and other stress-responsive systems. Maladaptation to acute or chronic stress represents a major risk factor for the development of psychiatric disorders. In the present study, we administered stress doses of hydrocortisone in a prospective, randomized, placebo-controlled double-blind study in patients undergoing cardiac surgery (CS) to examine the relationship between the use of glucocorticoids, plasma EC levels, and the occurrence of early postoperative cognitive dysfunction (delirium) and of later development of depression. Methods: We determined plasma levels of the ECs anandamide and 2-arachidonoylglycerol (2-AG) in CS patients of the hydrocortisone (n=56) and the placebo group (n=55) preoperatively, at postoperative day (POD) 1, at intensive care unit discharge, and at 6 months after CS (n=68). Postoperative delirium was diagnosed according to Diagnostic and Statistical Manual of the American Psychiatric Association IVth Edition (DSM-IV) criteria, and depression was determined by validated questionnaires and a standardized psychological interview (Structured Clinical Interview for DSM-IV). Results: Stress doses of hydrocortisone did not affect plasma EC levels and the occurrence of delirium or depression. However, patients who developed delirium on POD 1 had significantly lower preoperative 2-AG levels of the neuroprotective EC 2-AG (median values, 3.8 vs. 11.3 ng/ml; p=0.03). Preoperative 2-AG concentrations were predictive of postoperative delirium (sensitivity=0.70; specificity=0.69; cutoff value=4.9 ng/ml; receiver operating characteristic curve area=0.70; 95% confidence interval=0.54-0.85). Patients with depression at 6 months after CS (n=16) had significantly lower anandamide and 2-AG levels during the perioperative period. Conclusions: A low perioperative EC response may indicate an increased risk for early cognitive dysfunction and long-term depression in patients after CS. Glucocorticoids do not seem to influence this relationship

Effects of Single-Dose Prucalopride on Intestinal Hypomotility in Horses: Preliminary Observations

Abnormalities of gastrointestinal motility are often a challenge in horses; however, the use of prokinetic drugs in such conditions must be firmly established yet. For this reason we carried out a preliminary study on the effects of prucalopride on intestinal motor activity of horses with gut hypomotility. The effect of prucalopride per os by oral dose syringe (2 mg/100 kg body weight) was assessed by abdominal ultrasound (evaluating duodenal, cecal, and colonic motor activity) in six horses with gut hypomotility. After administration of prucalopride, a significant increase of contractile activity was found in the duodenum at 30 minutes (p = 0.0005), 60 minutes (p = 0.01) and 90 minutes (p = 0.01), whereas in the cecum and in the left colon the increase was only present at 60 minutes (p = 0.03, and p = 0.02, respectively). No changes from baseline heart and respiratory rate or behavior side effects were observed after administration of the drug and throughout the observation period. Prucalopride may be a useful adjunct to the therapeutic armamentary for treating hypomotile upper gut conditions of horses. Dosing information is however needed to establish its actual clinical efficacy and its proper effects on the large bowel in these animals

Informed consent decision-making in deep brain stimulation

Deep brain stimulation (DBS) has proved useful for several movement disorders (Parkinson’s disease, essential tremor, dystonia), in which first and/or second line pharmacological treatments were inefficacious. Initial evidence of DBS efficacy exists for refractory obsessive-compulsive disorder, treatment-resistant major depressive disorder, and impulse control disorders. Ethical concerns have been raised about the use of an invasive surgical approach involving the central nervous system in patients with possible impairment in cognitive functioning and decision-making capacity. Most of the disorders in which DBS has been used might present with alterations in memory, attention, and executive functioning, which may have an impact on the mental capacity to give informed consent to neurosurgery. Depression, anxiety, and compulsivity are also common in DBS candidate disorders, and could also be associated with an impaired capacity to consent to treatment or clinical research. Despite these issues, there is limited empirical knowledge on the decision-making levels of these patients. The possible informed consent issues of DBS will be discussed by focusing on the specific treatable diseases

Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson's disease

Background: Although the short-term benefits of bilateral stimulation of the subthalamic nucleus in patients with advanced Parkinson's disease have been well documented, the long-term outcomes of the procedure are unknown. Methods: We conducted a five-year prospective study of the first 49 consecutive patients whom we treated with bilateral stimulation of the subthalamic nucleus. Patients were assessed at one, three, and five years with levodopa (on medication) and without levodopa (off medication), with use of the Unified Parkinson's Disease Rating Scale. Seven patients did not complete the study: three died, and four were lost to follow-up. Results: As compared with base line, the patients' scores at five years for motor function while off medication improved by 54 percent (P<0.001) and those for activities of daily living improved by 49 percent (P<0.001). Speech was the only motor function for which off-medication scores did not improve. The scores for motor function on medication did not improve one year after surgery, except for the dyskinesia scores. On-medication akinesia, speech, postural stability, and freezing of gait worsened between year 1 and year 5 (P<0.001 for all comparisons). At five years, the dose of dopaminergic treatment and the duration and severity of levodopa-induced dyskinesia were reduced, as compared with base line (P<0.001 for each comparison). The average scores for cognitive performance remained unchanged, but dementia developed in three patients after three years. Mean depression scores remained unchanged. Severe adverse events included a large intracerebral hemorrhage in one patient. One patient committed suicide. Conclusions: Patients with advanced Parkinson's disease who were treated with bilateral stimulation of the subthalamic nucleus had marked improvements over five years in motor function while off medication and in dyskinesia while on medication. There was no control group, but worsening of akinesia, speech, postural stability, freezing of gait, and cognitive function between the first and the fifth year is consistent with the natural history of Parkinson's disease