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W B Severs

Publications and source records attributed to W B Severs.

At least 37 records · Page 2Linked to original sources
PubMed1994

Dexamethasone and ergonovine effects on cerebrospinal fluid pressure in conscious rats.

Prior work showed that intracerebroventricular (i.c.v.) infusions of artificial cerebrospinal fluid (aCSF), at a rate of 8 microliters/min x 10 min, elevated CSF pressure (CSFp) of conscious rats after a 2-hour delay. The rise was associated with an increased resistance to outflow and decreased intracranial compliance. When maintained by a continuous infusion of 0.25 microliter/min into each lateral ventricle, CSFp recordings can be made for 24 h and a higher CSFp occurs. Here, we pretreated rats with ergonovine or dexamethasone to determine their effects on the delayed CSFp rise. Ergonovine (0.5 mg/kg i.p.) pretreatment, in a 6-hour protocol using only the 10-min infusion, slightly reduced CSFp (p < 0.05, one-tail test) but the time course of the delayed rise in CSFp was unchanged (p > 0.05). Ergonovine increased intracranial compliance (p < 0.05) 20 min after infusion when CSFp was normal, but not when CSFp was elevated at 4 h (p > 0.05). Dexamethasone (40 micrograms i.m.) pretreatment was tested in the 24-hour protocol. It reduced (p < 0.05) normal CSFp during the 2-hour lag after infusion and the CSFp rise was reduced (p < 0.05) for about 8 h. However, the time course and ending CSFp were unchanged (p > 0.05). Thus, prior cerebral vasoconstriction or a steroidal anti-inflammatory drug have partial efficacy in reducing CSFp, but do not prevent the unknown events that precede the delayed CSFp rise after i.c.v. infusions.

Animals↗
PubMed1994

Cardiac noradrenergic mechanisms mediate GABA-enhanced ouabain cardiotoxicity.

Peripherally administered gamma-aminobutyric acid (GABA) alters cardiovascular function and has been reported to enhance ouabain-induced cardiotoxicity in vivo. Control and reserpinized rat hearts were perfused in vitro to determine if GABA directly evokes bradycardia by GABAA receptors, interacts with ouabain, and if noradrenergic mechanisms are required. Also, double-staining immunohistochemistry was employed to determine whether GABA-ergic and noradrenergic synthetic enzymes were juxtaposed within atrial tissue. The main results were as follows. GABA produced a dose-dependent bradycardia (p < 0.05) by stimulating GABAA receptors in Langendorff-perfused hearts. Reserpinized hearts were unresponsive (p < 0.05) to GABA, except at the highest dose (20 mg/ml). Ouabain-induced cardiotoxicity was enhanced (p < 0.05) by GABA in isolated control, but not reserpinized hearts. Lastly, glutamic acid decarboxylase and tyrosine hydroxylase immunoreactivities were in close proximity in atrial slices. Collectively, the results document that GABA causes bradycardia and enhances ouabain cardiotoxicity by modulating noradrenergic mechanisms in the isolated rat heart. Since the synthetic enzymes for GABA and norepinephrine were in close proximity in atrial tissue, these transmitters may interact under physiological conditions.

Analysis of Variance↗
PubMed1994

Angiotensin, vasopressin, and atrial natriuretic peptide in the rat eye.

Angiotensin (Ang), vasopressin (VP) and atrial natriuretic peptide (ANP) were assayed in the anterior uvea and retina from eyes of decapitated rats and rats perfused through the heart with phosphate buffered saline to remove peptides from blood and ocular fluids. All peptides were detected, and ANP was the most abundant. Uveal content of each peptide was greater than the retina. Perfusion did not affect ANP or VP content, but Ang was eliminated. Washout may explain the lack of immunohistochemical localization in the eye for Ang, but not VP. Also, washout does not account for available immunohistochemical data describing the localization of ANP in ocular tissue.

Angiotensin II↗
PubMed1993

Ouabain cardiotoxicity is enhanced by GABA in anesthetized rats.

Potential alteration of ouabain-induced cardiotoxicity by gamma-aminobutyric acid (GABA) in rats was tested by infusing ouabain for 10 min (0.7 mg/kg/min, i.v.) before or after continuous infusion of Ringer's solution with or without GABA (1 mg/min, i.v.). GABA evoked hypotension and bradycardia of similar magnitude under both conditions. The incidence of ouabain-induced ventricular fibrillation (VF) or cardiac arrest (CA) was similar in both groups. However, the time intervals to onset of VF and CA, in rats given ouabain before, but not after, GABA were shorter than in rats treated with Ringer's solution (p < 0.05). In experiments where baclofen (0.034 mg/min, i.v.) was infused after ouabain, hypotension and bradycardia occurred, but the incidence and times of ouabain-induced VF and CA were similar to control values. These results suggest that the enhancement in ouabain cardiotoxicity was mediated by GABAA receptors.

Anesthesia↗
PubMed1992

Mechanism of delayed intracranial hypertension after cerebroventricular infusions in conscious rats.

Prior studies showed that cerebroventricular infusions of artificial cerebrospinal fluid, 8 microliter/min for 10 min, followed by a 10 min rest and a 24 h infusion of 0.5 microliters/min, raised cerebrospinal fluid pressure (CSFp) of conscious, unrestrained rats after about 2 h. Here, we report that the 10 min infusion alone evoked a delayed, prolonged rise in CSFp. Pressure during the infusion itself rose and recovered quickly, as is usually reported. Pressure/volume tests, used to calculate resistance to outflow (Ro) and compliance (C), revealed that infusions increased Ro and decreased C, after a delay (P less than 0.05). The rise in CSFp after infusion was blocked by pretreatment with acetazolamide + ouabain (P less than 0.05), but the delayed changes in Ro and C were unaffected. We suggest that the 10 min infusion of a sterile, balanced salt solution has a primary effect that increases Ro; as CSF synthesis continues, C is exhausted and the delayed rise in CSFp ensues. This non-traumatic method of raising CSFp may be a useful method to study intracranial fluid dynamics.

Acetazolamide↗
PubMed1992

Resistance to outflow of cerebrospinal fluid after central infusions of angiotensin.

Infusions of artificial cerebrospinal fluid (CSF) into the cerebroventricles of conscious rats can raise CSF pressure (CSFp). This response can be modified by some neuropeptides. One of these, angiotensin, facilitates the rise in CSFp. We measured CSFp in conscious rats with a computerized system and evaluated resistance to CSF outflow during infusion of artificial CSF, with or without angiotensin, from the decay kinetics of superimposed bolus injections. Angiotensin (10 ng/min) raised CSFp (P less than 0.05) compared with solvent, but the resistance to CSF outflow of the two groups was similar (P greater than 0.05). Because CSFp was increased by angiotensin without an increase in the outflow resistance, a change in some volume compartment is likely. Angiotensin may raise CSFp by increasing CSF synthesis; this possibility is supported, since the choroid plexuses contain an intrinsic isorenin-angiotensin system. Alternatively, angiotensin may dilate pial arteries, leading to an increased intracranial blood volume.

Analysis of Variance↗
PubMed1992

The effect of head-down tilt and water immersion on intracranial pressure in nonhuman primates.

A headward fluid shift occurs in humans exposed to space-flight. This shift is thought to be the stimulus for the observed reduction in plasma volume, and may produce a sustained rise in intracranial pressure (ICP). In order to determine the effect of head-down tilt (HDT) and water immersion on intracranial pressure (ICP), five anesthetized rhesus monkeys were fitted with intracranial pressure-monitoring transducers and subjected to -6 degrees HDT followed by head-out thermoneutral (34.7 degrees) water immersion. ICP was elevated from 3.8 +/- 1.1 mm Hg in the horizontal control period to 5.3 +/- 1.3 mm Hg (p less than 0.05) during the 15 min pre-immersion HDT. When seated in the empty immersion tank, ICP stabilized at -6.3 +/- 1.3 mm Hg for the control period and increased to -2.2 +/- 1.9 mm Hg (p less than 0.05) when the water level was maintained for 30 min at the sternal notch. The ICP returned toward pre-immersion levels (-5.5 +/- 1.4 mm Hg) as the tank was drained. Mean blood pressure (MBP) remained constant during the pre-immersion tilt test. In the pre-immersion control period, MBP was 91 +/- 3 mm Hg compared to 90 +/- 4 mm Hg (p greater than 0.05) during immersion and 82 +/- 1 mm Hg (p less than 0.05) in the post-immersion recovery period. In summary, exposure of rhesus monkeys to either head-down tilt or water immersion produced a prompt rise in ICP during the stimulus period.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerospace Medicine↗
PubMed1991

Toxic effects of somatostatin in the cerebellum and vestibular nuclei: multiple sites of action.

This study demonstrates that somatostatin (SRIF), an endogenous peptide in vestibular nuclei and cerebellum, can produce both a dose-dependent death of Purkinje cells in distinct sagittal regions of cerebellar cortex and vascular infarcts centered selectively in the inferior vestibular nucleus. Alert, adult male rats were given a 5 microliters intracerebroventricular (i.c.v.) bolus of either SRIF alone (20 or 40 micrograms) or a combined dose of SRIF plus either arginine-vasopressin (AVP, 1 micrograms) or an AVP V1 antagonist, (1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)-tyrosine)-arginine 8-vasopressin (mcAVP, 1 micrograms), through an implanted cannula. After a 4-5 day survival, the brains were stained with the cupric-silver selective degeneration method. Two types of dose-dependent lesions were observed in the cerebellar and vestibular nuclei of these animals: degeneration of Purkinje cell responses in the cerebellar cortex and vascular infarcts in vestibular nuclei. These toxic responses were unaffected by application of AVP or mcAVP; hence, they can be attributed to actions of SRIF. The distribution of Purkinje cell degeneration varied with the SRIF dose in different cerebellar regions. Purkinje cell responses in lobules I-III were equivalent at both SRIF doses, and degeneration in the copula pyramis, paraflocculus and paramedian lobule emerged at the higher SRIF dose. Purkinje cells in the medial aspect of lobules IX-X had an intermediate sensitivity to SRIF intoxication. Degenerating Purkinje cells tended to be arranged in parasagittal bands in each region, suggesting parasagittal zonal variations in susceptibility to SRIF intoxication. By contrast, infarctions in the vestibular nuclei only appeared at the higher SRIF dose. These infarcts could be unilateral or bilateral and always involved the inferior vestibular nucleus at the level of the caudal margin of the acoustic tubercle; they often extended into the medial and lateral vestibular nuclei. The infarcts had a necrotic core that was infiltrated by non-neuronal elements. Thus, they appear to reflect a direct or neurally-mediated vascular response to the peptide.

Animals↗
PubMed1991

Cerebrospinal fluid pressure of conscious rats after venous constriction at the right atrium.

Thoracic shifts of blood stimulate diuresis and natriuresis during spaceflight. The available literature is not conclusive as to whether thoracic afferent neurons are essential for this response. Possibly, an acute elevation in cerebrospinal fluid pressure (CSF-p) activates central compensatory mechanisms. This is because central venous pressure is elevated by thoracic blood shifts and may reduce the pressure gradient for drainage of CSF into the venous sinuses. We tested whether rats with constriction of the venous return at the level of the heart (0.4 mm maximum diameter) had CSF-p different from sham-operated controls. CSF-p in the immediate postoperative period, as well as 1 and 10 days after surgery, were within normal limits and did not differ (p greater than 0.05). Blood collected at the end of the experiment showed no group differences (p greater than 0.05) in the hematocrit, or concentrations of sodium, potassium or vasopressin. Thus, changes in CSF-p, per se, appear to be insufficient to explain the cardiovascular or salt/water balance readjustments observed in spaceflight. It is likely that compensatory systems are highly redundant.

Animals↗
PubMed1991

Cerebrospinal fluid pressure in conscious head-down tilted rats.

Cerebrospinal fluid pressure (PCSF) was continuously measured in conscious male Sprague-Dawley rats gently restrained by a cotton towel. PCSF, evaluated in 15-min time blocks over a 3-h experiment, increased slightly (p less than 0.05) during the first 30 min of a control hour at 0 degree. There was a transient increase for about 5 min immediately after tilt (-45 degrees) that may have been due to head movement after the position change. However, PCSF was statistically unchanged (p greater than 0.05) during the 2nd (-45 degrees) hour and the 3rd (0 degree) recovery hour. The data show that the dynamics of intracranial pressure regulation can accommodate the acute cephalad fluid shift after tilting.

Animals↗
PubMed1990

Developing renal innervation in the spontaneously hypertensive rat: evidence for a role of the sympathetic nervous system in renal damage.

The spontaneously hypertensive rat (SHR) exhibits increased renal sympathetic nerve activity and neurotransmitter levels compared with the control Wistar-Kyoto rat (WKY). These renal nerve abnormalities have been implicated as the cause of hypertension in the SHR. The aims of the present study were to characterize the ontogeny of renal sympathetic innervation in SHR in order to determine any functional implications. Glyoxylic acid histofluorescent and radio-enzymatic norepinephrine assays demonstrated an accelerated development of renal innervation in newborn and 1-, 2-, 3- and 6-week-old SHR compared with WKY. Sympathetic nervous system function was blocked in developing male SHR by treating pups from days 0 to 14 with: (1) guanethidine, (2) combined alpha- and beta-receptor antagonists (prazosin and timolol), or (3) vehicle (5% sucrose). Blood pressure (mean), renal function (plasma creatinine) and histologic renal damage were assessed at 42 weeks of age. Although the blood pressure of the drug-treated rats remained elevated, renal damage was reduced and renal function was improved compared with control (sucrose-treated) SHR. The data demonstrate that the SHR kidney develops a precocious sympathetic innervation and that inhibition of the development of sympathetic function ameliorates renal damage independently of systemic hypertension.

Animals↗
PubMed1989

Immunoreactive atrial natriuretic peptide in the retina of rats and rabbits.

Immunoreactive atrial natriuretic peptide (ANP) has been detected in retinal tissue by radioimmunoassay, although it is unclear whether it was in retinal cells or represented residual peptide from blood and/or ocular fluids. We report here, using the immunoperoxidase method and a highly specific anti-rat ANP, that the peptide was localized consistently in the outer and inner plexiform layers of retinas of rats and rabbits. This information raises important issues: what are the implications for retinal function and, since blood-borne radioligands do not reveal retinal 'receptors', what is the endogenous target of retinal ANP?

Animals↗
PubMed1988

Long-term recording of cerebrospinal fluid pressure in freely behaving rats.

Literature values for 'normal', 'control', 'resting' or 'baseline' cerebrospinal fluid pressure (CSF-p) of rats reveal a large variability. Anesthesia, restraint, brief recordings at variable times from various sites and simultaneous infusions into the recording cannula may partly explain the variability. Here, we report values of continuous, day/night CSF-p recordings from a lateral ventricle in conscious, relatively unrestrained and freely behaving rats. The mean (+/- S.E.M.) daytime/nighttime values were 11.4 +/- 2.0 and 14.9 +/- 2.3 cm H2O, respectively (P less than 0.05). Minimum, but not maximum CSF-p's during the day were lower (P less than 0.05) than at night. The results provide a normative data base for studies designed to evaluate experimental or pathological phenomena affecting CSF-p.

Animals↗
PubMed1988

Diazepam attenuation of somatostatin-induced motor disturbances and neurotoxicity.

Intracerebroventricular somatostatin administration to conscious rats results in a characteristic motor abnormality (barrel rotation), convulsions that are frequently fatal and destruction of cerebellar Purkinje cells. This study demonstrates that each of these manifestations of this neuropeptide can be attenuated by pretreatment with diazepam (Valium, 5 mg/kg, i.p.) but not in vehicle-pretreated controls. Specifically, the incidence of mortality was reduced from 5/12 controls to 2/20 diazepam-treated rats, the incidence of barrel rotation was reduced from 6/12 controls to 2/20 diazepam-treated rats and the incidence of Purkinje cell death was reduced from 4/4 examined controls to 4/13 diazepam-treated animals. Vehicle pretreated rats did not differ from untreated rats. Thus, in addition to blocking somatostatin-induced motor dysfunction and mortality, diazepam offers significant protection from central neuronal cell death in the cerebellar cortex.

Animals↗
PubMed1988

Motor disturbances and neurotoxicity induced by centrally administered somatostatin and vasopressin in conscious rats: interactive effects of two neuropeptides.

Barrel rotation (BR) is an abnormal, long-axis rotation induced by intracerebroventricular (i.c.v.) injections of peptides, including somatostatin (SRIF) and arginine-vasopressin (AVP). This study examined the effects of two i.c.v. doses of SRIF and combined injections of SRIF and AVP in conscious, adult Wistar and Sprague-Dawley rats. Mortality after i.c.v. SRIF was dose-dependent; 0/16 rats died after a 20 microgram dose, while 21/43 died after 40 micrograms SRIF. On the other hand, BR incidence was similar after the two doses, but the hazard function of the BR latency data was shifted to the left by the higher dose. Although the incidence data imply that BR and mortality are independent, the hazard function of BR latency data is predictive of mortality. An interaction study employing a combined i.c.v. dose of 20 micrograms SRIF and 0.5 micrograms AVP established that the effects add non-linearly. This is illustrated by a marked increment in mortality (0/16 for 20 micrograms SRIF, 1/25 for 0.5 micrograms AVP and 12/18 for SRIF + AVP). The hazard plot shows a similar, non-linear interaction. In addition, SRIF, but not AVP, produced a characteristic pattern of Purkinje cell death in cerebellar regions projecting to the fastigial and lateral vestibular nuclei. These results imply that SRIF and AVP act at independent sites to produce BR and mortality, and that the effects summate non-linearly at a common central site. This raises the issue of whether these neuropeptides, endogenous in human CSF, interact to produce similar biological effects.

Animals↗
PubMed1988

Regional cerebral glucose utilization during vasopressin-induced barrel rotations or bicuculline-induced seizures in rats.

Regional cerebral metabolic rates of glucose (rCMRglu) were measured in conscious rats grouped according to three treatments: control, bicuculline (5.5 mg/kg s.c.), and intracerebroventricular arginine vasopressin (0.5 micrograms/5 microliter). Rats in the latter group were pre-exposed to the peptide 48 h earlier to render them 100% susceptible to a motor output termed barrel rotation (BR). Marked increases in rCMRglu occurred in all brain areas investigated after bicuculline. Increases after intracerebroventricular arginine vasopressin were smaller and occurred in fewer brain areas. Opposite to bicuculline, arginine vasopressin reduced rCMRglu in hippocampus and auditory cortex. The data confirm marked stimulation of rCMRglu during bicuculline-induced seizures and provide initial data for an endogenous peptide that causes BR. Generalized seizures and BR may share some neural substrates, but they produce distinct changes in rCMRglu. The rCMRglu changes are compatible with the interpretation that BR is initiated by brainstem/cerebellar areas that process visual-vestibular information, with subsequent involvement of higher brain structures.

Animals↗