Cardiovascular responses elicited by electrical stimulation of the amygdala central nucleus in the rabbit

Recent behavioral and anatomical evidence suggests the involvement of the amygdala central nucleus projection to medullary cardioregulatory nuclei in the expression of conditioned bradycardia during aversive Pavlovian conditioning in the rabbit^6,7,11,15. The present study sought to determine the extent to which electrical stimulation of the central nucleus produces bradycardia in the rabbit, and the extent to which any bradycardia elicited varies with stimulation at sites within as opposed to adjacent to the medial component of the central nucleus, the component from which the projection to cardioregulatory nuclei originates. Over 900 sites in 30 rabbits anesthetized with α-chloralose were explored. Monopolar stimulation (30–100 Hz; 0.5 ms pulse duration; 5.0 s train duration; 100–500 μA) at sites within the central nucleus produced bradycardia and depressor responses. Maximum bradycardia was produced from sites within the anterior, medial component of the nucleus. This respose usually began within one second of stimulus onset, reached peak magnitude within two seconds of stimulus onset and in many instances was followed by a slight tachycardia following stimulus termination. The accompanying depressor responses occurred at longer latencies than the bradycardia responses. The responses persisted following artificial ventilation and immobilization by Flaxedil and were attenuated by i.v. injections of atropine methylnitrate. While bradycardia and depressor responses were elicited from sites immediately dorsal, ventral and lateral to the medial central nucleus, these responses were of markedly less magnitude than those elicited from the medial component. The results are consistent with previous evidence which suggests a contribution for the central nucleus in the expression of cardiovascular responding during aversive Pavlovian conditioning in the rabbit.     

Satisfaction,quality of life and therapy adherence assessment in real life patients transitioning from vitamin K antagonists to direct oral anticoagulants

Journal of Thrombosis and Thrombolysis - Anticoagulant therapy has undergone a significant change since direct oral anticoagulants (DOACs) introduction. Their obvious advantages including the fixed...     

Morphometric studies of the aged hippocampus: I. Volumetric analysis in behaviorally characterized rats

The present investigation examined the structural integrity of the aged hippocampus by using computer-aided morphometry to quantify the volume of principal hippocampal circuits in young, mature adult, and aged Long-Evans rats. A key feature of the experimental design was that the status of hippocampal-dependent learning and memory was documented prior to histologic evaluation. The following regions, which were visualized by using Timm staining, were included in the analysis: 1) outer portions of the dentate gyrus molecular layer (OML) innervated by the lateral entorhinal cortex, 2) middle portions of the molecular layer (MML) that receive input from the medial entorhinal cortex, 3) the commissural/associational zone (IML) immediately adjacent to the granule cell layer, and 4) the hilus and mossy fiber projection to the CA3 pyramidal cell field (MF). To identify morphometric changes that emerge during the same segment of the life span as age-related learning impairment, analysis of the volumetric results focused on comparisons between the mature adult group and the aged group. Among the individual regions that were analyzed, age-related decreases in total volume were restricted to the MML. This effect, however, occurred against a background of other, subtle changes that, together, reflected substantial reorganization in the normal balance of hippocampal circuitry. Age-related decreases in the proportion of the molecular layer (ML) that comprises the MML were accompanied by a corresponding increase in relative IML volume. The ratio between the volumes of the MML and the MF also displayed significant age-related decline. Overall, aging affected septal levels of the hippocampus disproportionately, and, with the exception of MML/MF volume ratio, the temporal hippocampus was spared. Finally, the status of spatial learning among the aged animals correlated selectively with decreases in the MML/ML and MML/MF ratios. These results demonstrate that the effects of aging are regionally selective and circuit specific, and they suggest that connectional reorganization may contribute to age-related decline in the computational functions of the hippocampus. J. Comp. Neurol. 403:459–470, 1999. © 1999 Wiley-Liss, Inc.     

Myoclonus in mitochondrial disorders

Myoclonus is a possible manifestation of mitochondrial disorders, and its presence is considered, in association with epilepsy and the ragged red fibers, pivotal for the syndromic diagnosis of MERRF (myoclonic epilepsy with ragged red fibers). However, its prevalence in mitochondrial diseases is not known. The aims of this study are the evaluation of the prevalence of myoclonus in a big cohort of mitochondrial patients and the clinical characterization of these subjects. Based on the database of the “Nation‐wide Italian Collaborative Network of Mitochondrial Diseases,” we reviewed the clinical and molecular data of mitochondrial patients with myoclonus among their clinical features. Myoclonus is a rather uncommon clinical feature of mitochondrial diseases (3.6% of 1,086 patients registered in our database). It is not strictly linked to a specific genotype or phenotype, and only 1 of 3 patients with MERRF harbors the 8344A>G mutation (frequently labeled as “the MERRF mutation”). Finally, myoclonus is not inextricably linked to epilepsy in MERRF patients, but more to cerebellar ataxia. In a myoclonic patient, evidences of mitochondrial dysfunction must be investigated, even though myoclonus is not a common sign of mitochondriopathy. Clinical, histological, and biochemical data may predict the finding of a mitochondrial or nuclear DNA mutation. Finally, this study reinforces the notion that myoclonus is not inextricably linked to epilepsy in MERRF patients, and therefore the term “myoclonic epilepsy” seems inadequate and potentially misleading. © 2014 International Parkinson and Movement Disorder Society     

Lesions of basolateral amygdala impair extinction of CS motivational value,but not of explicit conditioned responses,in Pavlovian appetitive second-order conditioning

The basolateral amygdala (BLA) is important for the modification of the motivational significance of events through associative learning. In previous work, we found that BLA was critical for the acquisition of conditioned reinforcement value to a visual conditioned stimulus (CS) paired with food. Unlike normal rats, rats with neurotoxic lesions of the BLA failed to acquire Pavlovian second-order conditioning to an auditory stimulus paired with the first-order visual CS in the absence of food. In this experiment, we examined the role of BLA in the extinction of the previously acquired conditioned reinforcement value of a Pavlovian CS. Rats received first-order visual CS-food pairings prior to either BLA- or sham-lesions. Subsequent CS-alone extinction training reduced the ability of the visual CS to reinforce second-order conditioning of an auditory stimulus in the sham-lesioned rats, but not in the BLA-lesioned rats. Despite this persistence of the conditioned reinforcement value of the visual first-order CS in the BLA-lesioned rats, no effects of the lesions were observed on extinction of the explicit behavioural conditioned responses elicited by that CS.     

Nucleotide-mediated calcium signaling in rat cortical astrocytes: Role of P2X and P2Y receptors

ATP is the dominant messenger for astrocyte-to-astrocyte calcium-mediated communication. Definition of the exact ATP/P2 receptors in astrocytes and of their coupling to intracellular calcium ([Ca(2+)](i)) has important implications for brain physiology and pathology. We show that, with the only exception of the P2X(6) receptor, primary rat cortical astrocytes express all cloned ligand-gated P2X (i.e., P2X(1-5) and P2X(7)) and G-protein-coupled P2Y receptors (i.e., P2Y(1), P2Y(2), P2Y(4), P2Y(6), and P2Y(12)). These cells also express the P2Y-like UDP-glucose receptor, which has been recently recognized as the P2Y(14) receptor. Single-cell image analysis showed that only some of these receptors are coupled to [Ca(2+)](i). While ATP induced rapid and transient [Ca(2+)](i) increases (counteracted by the P2 antagonists suramin, pyridoxal-phosphate-6-azophenyl-2'-4'-disulfonic acid and oxidized ATP), the P2X(1)/P2X(3) agonist alphabetameATP produced no changes. Conversely, the P2X(7) agonist BzATP markedly increased [Ca(2+)](i); the presence and function of the P2X(7) receptor was also confirmed by the formation of the P2X(7) pore. ADP and 2meSADP also produced [Ca(2+)](i) increases antagonized by the P2Y(1) antagonist MRS2179. Some cells also responded to UTP but not to UDP. Significant responses to sugar-nucleotides were also detected, which represents the first functional response reported for the putative P2Y(14) receptor in a native system. Based on agonist preference of known P2 receptors, we conclude that, in rat astrocytes, ATP-induced calcium rises are at least mediated by P2X(7) and P2Y(1) receptors; additional receptors (i.e., P2X(2), P2X(4), P2X(5), P2Y(2), P2Y(4), and P2Y(14)) may also contribute.     

Prognostic value of cutaneous reinnervation with GAP-43 in oxaliplatin-induced neuropathy

Journal of Neurology - Oxaliplatin-induced neuropathy (OIN) implies axonal damage of both small and large sensory nerve fibers. We aimed at comparing the neurophysiological changes occurred after...     

Erenumab for the preventive treatment of chronic migraine complicated with medication overuse headache: an observational,retrospective, 12-month real-life study

Background

Erenumab is a monoclonal antibody blocking the calcitonin gene–related peptide receptor, which has been approved for the preventive treatment of chronic migraine (CM). The aim of this study was to explore the safety and effectiveness of erenumab in patients suffering from CM and medication overuse headache (MOH) in a real-life setting, up to 1 year.

Methods

Data regarding 81 patients treated with erenumab were retrospectively analyzed. Every 3 months, the following variables were collected: the mean number of headache days per month (headache index (HI)), the average number of painkillers taken per month (analgesic consumption (AC)), the mean number of days with painkiller consumption (number of days on medication (NDM)), the headache intensity (numeric rating scale (NRS) score), the 6-item Headache Impact Test (HIT-6), and the Self-Reported Instrument to Assess Work-Related Difficulties in Patients With Migraine (HEADWORK) scores.

Results

The HI, AC, and NDM and the NRS, HIT-6, and HEADWORK scores were significantly lower at every time point from the 3rd month onward compared to baseline (all P < 0.0001). No significant differences were found between patients who underwent painkiller detoxification before starting erenumab and those who did not (all P > 0.05). No significant differences were found between patients taking erenumab in combination with other preventive treatments and the ones taking it alone (all P ≥ 0.05). Five patients dropped out because of adverse events, which resolved after stopping erenumab.

Conclusion

Erenumab was safe and effective for CM complicated with MOH. Painkiller withdrawal and the association with other preventive treatment(s) seem useless.