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Background: Interleukin-1β (IL-1β) increases necrotic neuronal cell death in the CA1 area after induced status epilepticus (SE) in developing rats. However, it remains uncertain whether IL-1β has a similar effect on the hippocampal dentate gyrus (DG). In this study, we analysed the effects of IL-1β on 14-day-old Wistar rats experiencing DG neuronal death induced by SE., Methods: SE was induced with lithium-pilocarpine. Six hours after SE onset, a group of pups was injected with IL-1β (at 0, 0.3, 3, 30, or 300ng/μL) in the right ventricle; another group was injected with IL-1β receptor (IL-1R1) antagonist (IL-1Ra, at 30ng/μL) of IL-1RI antagonist (IL-1Ra) alone, and additional group with 30ng/μL of IL-1Ra plus 3ng/μL of IL-1β. Twenty-four hours after SE onset, neuronal cell death in the dentate gyrus of the dorsal hippocampus was assessed using haematoxylin-eosin staining. Dead cells showed eosinophilic cytoplasm and condensed and fragmented nuclei., Results: We observed an increased number of eosinophilic cells in the hippocampal DG ipsilateral to the site of injection of 3ng/μL and 300ng/μL of IL-1β in comparison with the vehicle group. A similar effect was observed in the hippocampal DG contralateral to the site of injection of 3ng/μL of IL-1β. Administration of both of IL-1β and IL-1Ra failed to prevent an increase in the number of eosinophilic cells., Conclusion: Our data suggest that IL-1β increases apoptotic neuronal cell death caused by SE in the hippocampal GD, which is a mechanism independent of IL-1RI activation., (Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

In recent decades, many compounds with central dopaminergic activity have been designed, synthesized and evaluated pharmacologically. However, it has not been possible to obtain a drug able to improve or cure diseases involving dopaminergic regulation in the central nervous system, such as Parkinson's disease and schizophrenia, among others. Taking into consideration the term "atypical pharmacophore" and from the compound 5, the aralkyl fragment was incorporated, and the compounds 10, 11, 13a-h and 14a-h were synthesized. Both the compounds 10 and 13a-h under its methoxylated form and the compounds 11 and 14a-h under the phenolic form, were evaluated to determine their pharmacologically agonistic and antagonistic effects on central dopaminergic activity. For this, the effect of intracerebroventricular injection of said compounds on the hydromineral balance and stereotyped behavior in rats, was determined. The results of the preliminary pharmacological evaluation show a centrally acting action through dopamine mechanisms, in which the compounds 10, 11, 13d-h and 14a showed responses as agonists, whereas compounds 14b-h, had responses as antagonists.

Cancer pain is a frequent medical problem in our society. This syndrome affects from 80 to 90% of cancer patients and can be solved with relatively simple measures in 90% of the cases. Approximately 40% of cancer patients reported to be unsatisfied with the physician or nurse about their pain management. For these reasons, we gathered a task force in order to generate practice guidelines based on medical evidence and on the opinion of experts in this area. These guidelines were generated by a task force of 31 physicians who were leaders in this field and based on 599 papers selected by a previous literature search. This group evaluated the results of this search in three work sessions, during which a level of evidence was assigned to each recommendation.

Introduction: Subacute sclerosing panencephalitis (SSPE) is a chronic neurodegenerative disease secondary to an infection of the central nervous system by the measles virus, with no effective treatment. The introduction of therapy with intraventricular interferon alpha (IFN-alpha) and its later association with ribavirin aroused new expectations. In experimental studies the two drugs were seen to exert a synergic effect in reducing viral replication. Therapeutic studies carried out in patients with SSPE with the two pharmaceuticals have offered contradictory findings., Case Reports: We present the cases of two patients with an early-onset, fast progressing form of SSPE, who were treated with a combined regime of oral isoprenosin, intraventricular IFN-alpha and ribavirin, which was administered intravenously in one case and intraventricularly in the other. At the beginning of treatment the patients' deterioration stabilised briefly and temporarily, but then renewed its progress., Conclusions: Combined therapy with intraventricular IFN-alpha and ribavirin was not effective in our patients. The late onset and rapidly progressing symptoms of the disease may have had an effect on the poor results obtained.

Objective: To review the most appropriate doses and routes within cerebrospinal - intrathecal, intraventricular, epidural - administration for drugs most commonly used in daily practice as reported in the literature, with particular emphasis on pediatric use., Method: A systematic, sequential, repetitive search of tertiary sources primarily and then primary sources in MEDLINE (Pubmed) and GOOGLE by combining each individual drug name with "intrathecal OR intraventricular OR epidural", and then differentiating between data referring to the pediatric and adult populations., Results: In all, 28 drugs within 5 groups are described: anti-infectious, analgesic, and anti-neoplastic agents, corticoids, and other. Doses are categorized by population type: pediatric (newborns, infants, children) and adult., Conclusions: The relevance of this administration route and its potential use do not correlate with its scant reporting in the literature, except for anti-infectious, analgesic and cytostatic agents. Only five of these drug types are officially approved for cerebrospinal administration according to their prescribing information (polymyxin B, colistin, cytarabine, baclofen and morphine). Of these, only polymyxin B and colistin are indicated for the whole of the pediatric population.

The study of cerebrospinal fluid (CSF) dynamics is central to the diagnosis of adult chronic hydrocephalus (ACH). At present, many neurology and neurosurgery departments use one or more tests to guide diagnosis of this syndrome and to predict patient response to shunting. In specialised centres, the study of CSF dynamics is combined with continuous intracranial pressure (ICP) monitoring. Determination of several variables of CSF dynamics and definitions of qualitative and quantitative characteristics of ICP can be used to establish whether the hydrocephalus is active, compensated or arrested. CSF dynamics and ICP monitoring can also be used to check the correct functioning of the shunt and can be of use in the clinical management of patients with pseudotumor cerebri. Moreover, ICP monitoring is used to guide the treatment of several acute neurological processes. The aim of this review is to describe the fundamentals of CSF dynamics studies and the bases of continuous ICP monitoring. The advantages and disadvantages of several hydrodynamic tests that can be performed by lumbar puncture, as well as the normal and abnormal characteristics of an ICP recording, are discussed.

The animal model of aged monkeys is a good homologue of Alzheimer's disease in humans, in which it has been shown that there is disproportionate slowing of the EEG when compared with healthy subjects paired for age. This is found both on the conventional EEG and quantitatively. In the latter, relative energy has been the measurement most commonly used for diagnosis and follow-up with various treatments. The follow-up parameters evaluated in this study were: absolute and relative energy of the quantitative EEG (EEGq) obtained in an aged (39 year old) baboon (Papio hamadryas) before and after infusion of intraventricular nerve growth factor (NGF). These findings were compared with those of a young animal (6 year old) of the same species, treated in the same way. Since the animals were first anaesthetized with ketamine and diacepam so as to be able to carry out the study, we used a cerebral function analyzer which allowed us to ascertain that the changes found on analysis of the EEGq were not due to the depth of anaesthesia. The analyzer evaluated the tendencies of amplitude and frequency of the EEG, which is a method widely used for the indirect evaluation of the level of anaesthesia.

A study was made relating the anticholinergic action of alpha 2-adrenoceptor agonist clonidine on the cardiovascular responses to i.c.v. injection of neostigmine, a quaternary anticholinesterase, in conscious rats. The cholinergic agent neostigmine (0.1-1 microgram i.c.v.) induced a dose-dependent pressor and bradycardic responses in the rats. Clonidine (10 micrograms.kg-1 i.v.), given 30 min previous the anticholinesterase, failed to modify the pressor effect of neostigmine (0.1-1 microgram i.c.v.) but prevented the bradycardia. On the other side, the i.c.v. administration of clonidine (3 micrograms), given 15 min before neostigmine, only prevented the bradycardic effect of neostigmine (0.3 microgram i.c.v.) but not the central pressor action of this drug. The results support the idea that clonidine has an anticholinergic action in the rat. However, prevention by clonidine of central cholinergic bradycardia suggests different cholinergic-adrenergic interaction on the cardiovascular responses elicited by central administration of cholinergic agents.

Previous references showed that the histamine injected peripherically produced a deterioration of the learning in experimental animals. The effects of 100 and 200 micrograms of histamine administered in the cerebral lateral ventricle, have been tested using an experimental paradigm which isolated attentional, motivational, and motor factor from the complex learned behavior. The obtained results showed to be similar to those produced by peripheric injection, and demonstrated a worsening in attentional, motivational, and motor parameters.

The effect of two potent neurotoxic agents for 5HT neurons, 5,6-DHT and 5,7-DHT, intraventricularly injected, has been studied on the values and rhythm of plasmatic corticosterone secretion in the male Wistar rat model, along an entire day: 4 a.m., 8 a.m., noon, 5 p.m. and midnight. The dose administered for each drug was 100 micrograms/animal in a single injection. The levels of corticosterone were determined 15 and 30 days post-injection. The effects observed for both drugs were similar at similar times: highly significant decreases in all the studied points which fall under the same line of secretion and evince an absolute inhibition of the cyclic rhythm. There are no significant differences among the values obtained with different drugs at various times. The contents of NA and 5HT significantly decrease for both drugs especially those of the 5HT on the 15th day. 30 days after the injection there is a small recovery of 5HT, but differences with control values are still significant. On the other hand the recovery of NA was almost total (near 100%). The results are discussed within the highly controversial frame of the influence of central 5HT neurons on the various types of secretion of the hypothalamic-pituitary-adrenal axis. The data obtained with this "chronic model" are confronted with those from other authors who have used drugs with transitory effect on the 5HT brain metabolism.

Single and combined effects of intracerebroventricular bolus injection of Ang. II (200 ng), ACh (6 micrograms) and met-enkephalin (50 micrograms) on mean arterial pressure (MAP), was tested in Sprague-Dawley albino rats. A metallic cannula was implanted in the third ventricle according to standard stereotaxic procedures under pentobarbital anesthesia (35 mg/kg). On the third day, the animal was anesthetized again, a carotid artery was cannulated and connected to a pressure transducer for recording of MAP. Ang. II increased MAP; ACh produced a significant increase in the initial 5 minutes after injection and met-enkephalin did not induce any significant changes in MAP. The combined effect showed interesting results. Instead of a potentiation of the rise in MAP, Ang. II and ACh, when given together, did not show any significant changes. Also, met-enkephalin blocked the hypertensive response due to Ang. II, if given combined. This is compatible with an inhibitory action of met-enkephalin on an angiotensinergic neuronal system. A simplified hypothetical model that explains the findings described above is proposed as a working hypothesis.

Pharmacokinetics of cadmium chloride (109Cd) in blood and cerebral structures in male Wistar rats is studied. Blood kinetics is obtained after intravenous administration of 20 microCi 109Cd; the element is distributed according to an open bicompartimental model with a high alpha deposition constant. The half-life of the alpha-phase is 0.043 hours and the half-life of the beta-phase is 5.54 hours. The kinetics of 109Cd in cerebral structures is calculated after injection of a total amount of 1 microCi in both lateral ventricles. Cadmium radionuclide in cerebral structures of the rat is rapidly fixed from the cerebral fluid, but released slowly. The structure of major accumulation is striatum and that of minor accumulation is cerebellum.

Some papers have been published in relation to alternative models of experimental pain in animals. In this work, with the aim of proving the validity, safety, reproducibility and objectivity of this model, we have compared the behaviour of the animal under the formaldehyde test before and after the intracerebroventricular administration of morphine, proving itself as an ideal model for the study of chronic pain caused by an excess of nociception.

A case of Candida meningitis in a premature infant treated with amphotericin B IV for 41 days, resulted in negative CSF cultures after 5 days of therapy. Amphotericin B was also given intraventricularly for 21 days; purulent meningitis was a complication from this kind of therapy. Psychometric evaluation showed a mental age of 3 months in a chronological age of 7 months. Only one premature infant has been reported in the literature with intraventricular amphotericin B treatment. A review of Candida meningitis diagnosed before death in infants less than 1 year of age and a discussion of the modern therapy is presented.