Cerebrospinal Fluid Of Animals Research Articles

Available evidence does not support serosorting as an HIV risk reduction strategy

Recent data highlighted the association between penetration of antiretrovirals in the central nervous system (CNS) and neurocognitive impairment in HIVpositive patients. Existing antiretrovirals have been ranked according to a score of neuropenetration, which was shown to be a predictor of anti-HIVactivity in the CNS and improvement of neurocognitive disorders [1]. Main factors affecting drug penetration are known to be protein binding, lipophilicity and molecular weight [2]. Moreover, active translation by membrane transporters (such as p-glycoprotein) could be a key mechanism of passage [3]. The use of raltegravir (RGV), a novel antiretroviral drug targeted to inhibit the HIV preintegrase complex, is increasing worldwide due to its efficacy and tolerability. However, penetration of RGV in the CNS has not been yet elucidated. In fact, prediction of RGV neuropenetration according to molecular characteristics is controversial. Intermediate protein binding (83%) and large volume of distribution (273 l) could suggest a high distribution beyond extracellular spaces [4]. On the contrary, low lipophilicity (oil/water partition coefficient at pH 7.4 of 2.80) and intermediate molecular weight (482.51 Da) suggest a limited diffusion. Furthermore, in-vitro studies suggest that RGV is substrate of p-glycoprotein, although this efflux pump has not been identified to significantly affect plasma pharmacokinetics [5]. In any case, no data concerning RGV passage into cerebrospinal fluid of animals or humans have yet been published.

RELATIONSHIP BETWEEN CEREBROSPINAL FLUID PRESSURE AND PLASMATIC ADH

In a healthy human being, the extracellular volume is kept constant by homeostatic systems. One of these is represented by the antidiuretic hormone (ADH). ADH release is modulated by osmoreceptors and baroreceptors which respond to an increase in osmolality of extracellular fluid and a decrease in blood volume, respectively. In previous studies we investigated the existence of additional structures sensitive to plasma volume modifications. We found evidence of the presence of such receptors in the inner ear, with nervous connections to supraoptic and paraventricular nuclei. However, the possibility that the cerebral ventricle wall contained stretch sensors could not be excluded. To test our hypothesis, we studied 19 rats divided into three groups: Group 1 (n=7), Group 2 (n=7) and Group 3 (control groupn=5). In each rat, under total anaesthesia, a femoral cannula was inserted into the left artery and a 22 gauge stainless steel cannula was implanted into the left cerebral ventricle. In the first group an isotonic fluid, similar to the animal's cerebrospinal fluid (CSF), was infused intracerebroventricularly (ICV) at a rate of 0.6 μl min−1continuously for 6 h. In the second group, under the same conditions, CSF was aspirated; the third group was used as the control. In all animals, plasma modifications of ADH (pADH), osmolality (pOSM), Na+(pNa+) and K+(pK+) were evaluated before and after the experimental procedures. Mean arterial pressure (MAP) and heart rate (HR) were recorded throughout the experiment. At the end of the experiment no significant changes in pNa+, pK+, MAP and HR were observed. Plasma osmolality was significantly lower in Group 2 before and during the experimental procedure, since we deliberately expanded the volume in animals of Group 2 to partially suppress ADH, in order to evaluate its modifications. Plasma ADH fell in the first experimental group (−37.4%±6.3sem) after the ventricular pressure had been increased, and rose in the second (+47.3%±14.7sem) after ventricular decompression. These changes were statistically significant in comparison with those occurring in control subjects (−0.9±18.9sem;P=0.07 andP=0.03, respectively). These results suggest the presence of additional volume receptors probably located in the cerebral ventricles, capable of controlling ADH. The importance of these receptors in physiological situations of plasma volume contraction or expansion remains to be established.

Neural angiostrongylosis in three captive rufous bettongs (Aepyprymnus rufescens).

Neurological disease attributed to migration of the rat lungworm (Angiostrongylus cantonensis), is described in three captive rufous bettongs (Aepyprymnus rufescens). Clinical signs, including ascending paralysis and multifocal neurological deficits, were similar to those seen in other species. Histologically, the severity of meningoencephalomyelitis ranged from mild to moderate. In one animal cerebrospinal fluid contained a high percentage of eosinophils but peripheral blood cell counts were within normal limits. Treatment with dexamethasone, diazepam and vitamin E was unsuccessful. The prognosis for bettongs with this disease is poor. The susceptibility of this species to this disease has implications for enclosure design.

Reversal of experimental autoimmune encephalomyelitis with a hydroxamate inhibitor of matrix metalloproteases.

Gelatinases, belonging to the matrix metalloproteases, contribute to tissue destruction in inflammatory demyelinating disorders of the central nervous system such as multiple sclerosis. We used experimental autoimmune encephalomyelitis (EAE) as an animal model to evaluate the effect of a hydroxamate matrix metalloprotease inhibitor (GM 6001) on inflammatory demyelination. A single dose of the inhibitor, given intraperitoneally, provided sufficient levels in the cerebrospinal fluid of animals with EAE to induce at least a partial inhibition of the gelatinase activity in the cerebrospinal fluid. When administered daily either from the time of disease induction or from the onset of clinical signs, GM 6001 suppressed the development or reversed clinical EAE in a dose-dependent way, respectively. Animals returned to the same clinical course as the nontreated group after cessation of treatment. Animals treated from the onset of clinical signs had normal permeability of the blood-brain barrier, compared with the enhanced permeability in nontreated animals. These results indicate that matrix metalloprotease inhibition can reverse ongoing EAE. This effect appears to be mediated mainly through restoration of the damaged blood-brain barrier in the inflammatory phase of the disease, since, the degree of demyelination and inflammation did not differ between the treatment groups.

Antigenicity and protective effects of type 3 pneumococcal polysaccharide in rats

The response to type 3 pneumococcal polysaccharide vaccination, the protective effect of type 3 pneumococcal polysaccharide vaccination, and the ability of hemagglutinating antibody to type 3 pneumococcal polysaccharide to cross the blood-brain barrier were studied in rats. Hemagglutinating antibody response to vaccination with type 3 pneumococcal polysaccharide was found to be dependent on the dose and route of inoculation. Intraperitoneal vaccination with type 3 pneumococcal polysaccharide protected the rats from subsequent intraperitoneal challenge with type 3 Streptococcus pneumoniae but had no effect after intracisternal challenge with type 3 S. pneumoniae. In the presence or absence of sterile meningeal inflammation, hemagglutinating antibody could not be found in cerebrospinal fluid of animals vaccinated intraperitoneally with type 3 pneumococcal polysaccharide. These results suggest that type 3 pneumococcal polysaccharide is antigenic in rats and intraperitoneal vaccination with type 3 pneumococcal polysaccharide does not protect against experimental meningitis because antibodies do not cross the blood-brain barrier.

Studies in the Movement of Isotopes RI131SA and Na24from Ventricular CSF Fluid

SUMMARYThe author discusses several experiments in tracing the bulk movement of cerebrospinal fluid in animals and in human subjects by the injection of radio‐active isotopes.

Amino acid transport by choroid plexus in vitro.

Abstract—Choroid plexus from mongrel cats was incubated from 1 to 120 min in artificial cerebrospinal fluid containing α‐amino[1‐14C]isobutyric acid. The uptake of α‐amino [1‐14C]isobutyric acid occurred against a concentration gradient, was saturable, dependent on metabolic energy, and inhibited by natural amino acids. These results indicate that a transport mechanism is present in choroid plexus which could serve to regulate amino acid concentration in the cerebrospinal fluid of animals.

Measurement of acid monoamine metabolites in human and animal cerebrospinal fluid.

SUMMARYTechniques for measuring 5‐hydroxyindolacetic acid (5‐HIAA) and homovanillic acid (HVA) have been modified to permit the use of smaller samples for measuring these acid monoamine metabolites in human and animal CSF. Levels of both HVA and 5‐HIAA were approximately three times as high in human ventricular CSF as in human lumbar CSF. Lumbar CSF levels of 5‐HIAA in neurologic patients were significantly higher than those in psychiatric patients. Values were obtained for HVA in dog cisternal CSF and for 5‐HIAA in dog, rabbit, and cat cisternal CSF.

Stimulation and sensitization of the isolated Venus heart by cerebrospinal fluid.

5-Hydroxytryptamine was not detected in animal cerebrospinal fluid after amine oxidase inhibitors, reserpine, or both. Both human and animal cerebrospinal fluid can produce a stimulating effect on the clam heart which is not due to 5-hydroxytryptamine. Cerebrospinal fluid also has the property of increasing the sensitivity of the clam heart to 5-hydroxytryptamine.

Spirochæte ‐ like structures in the cerebro‐spinal fluid of animals used for experimental purposes

Spirochæte ‐ like structures in the cerebro‐spinal fluid of animals used for experimental purposes

PUNCTURE OF THE CISTERNA MAGNA

A situation occasionally arises in which lumbar puncture is either impossible, impracticable or insufficient, when access to upper reservoirs of cerebrospinal fluid are desirable or imperative. The necessity of reaching subarachnoid space at other points than lumbar sac has led to such procedures as puncture in thoracic and cervical regions, puncture through sphenoidal fissure and intraventricular puncture. In literature one finds no mention of cisterna puncture1as a clinical procedure, although it has for long been routine method for obtaining cerebrospinal fluid in animals, and drainage of cisterna has been employed by a number of surgeons.2 With other routes besides lumbar and ventricular, writer has had no experience, all seeming of too hazardous a nature for other than extremely rare application. Cisterna puncture, reaching as it does the distributing center of cerebrospinal fluid system should, however,