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R F Tuma

Publications and source records attributed to R F Tuma.

At least 19 recordsLinked to original sources
PubMed2000

Quantitative changes in interleukin proteins following focal stroke in the rat.

The aim of the present study was to quantitate the temporal changes in protein concentration for interleukin (IL)-1alpha, IL-1beta, IL-1ra, and IL-6 from 1 h to 15 days following focal ischemia. Protein expression was evaluated by enzyme-linked immunosorbent assay utilizing newly available rat antibodies. There were no detectable basal levels of IL-1alpha, 1L-1beta, or IL-6 in the sham-operated or non-ischemic control cortex. IL-1beta (increased significantly (P<0.05) as early as 4 h and peaked at 3 to 5 days. IL-1alpha (increased significantly (P<0.05) at 3 days. IL-6 increased early and peaked at 24 h (P<0.05). IL-1ra increased significantly (P<0.05) over basal levels from 12 h to 5 days. The present study provides the first quantitative determination of interleukin protein concentrations in the rat brain following focal stroke and demonstrates that this technology is now available for mechanistic studies in neuroprotection.

Animals↗
PubMed1999

Polynitroxylated hemoglobin-based oxygen carrier: inhibition of free radical-induced microcirculatory dysfunction.

Reactive oxygen species have been identified as key mediators of leukocyte/endothelial cell interaction under various pathological conditions and diseases such as ischemia/reperfusion injury, inflammation, and after exposure to cigarette smoke. Consequently, antioxidants have been shown to successfully prevent the sequelae of these conditions, ranging from tissue infarction to atherogenesis. In this study we investigated whether, via its established superoxide dismutase-like activity, a novel polynitroxyl hemoglobin-based oxygen carrier (PNH), could affect the stimulation of leukocyte rolling and adhesion to endothelial cells in response to cigarette smoke. Using the dorsal skin fold chamber model for intravital microscopic observation of leukocyte/endothelium and -/platelet interactions in hamsters, we could demonstrate that cigarette smoke exposure elicited in control animals the rolling and adhesion of leukocytes along the endothelium of postcapillary venules and also of arterioles, as well as the formation of leukocyte/platelet aggregates. In contrast to the hemoglobin based oxygen carrier (HBOC) alone, that showed no therapeutic benefit, PNH significantly inhibited these proadhesive processes secondary to cigarette smoke. Also, PNH significantly reduced the formation of leukocyte/platelet aggregates in the blood stream of the cigarette smoke-exposed animals. These effects are not due to changes in microhemodynamic conditions, because wall shear rates remained unchanged in all three groups of animals.

Animals↗
PubMed1999

The effects of pentoxifylline on spinal cord blood flow after experimental spinal cord injury.

Previous clinical and experimental investigations have suggested that pentoxifylline, a methylxanthine, can improve cerebrovascular circulation and reduce cerebral edema in cerebrovascular disorders. Pentoxifylline's mechanism of action includes such rheologic effects as enhanced red cell deformability, alterations in leukocyte activation, and modification of coagulation parameters. The purpose of our investigation was to determine the effects of pentoxifylline in an experimental spinal cord injury model. A compression device was used to cause a reproducible spinal cord injury in adult female albino rats. Spinal cord blood flow was monitored using a laser Doppler flow meter pre- and postinjury for 4 hours. The experimental group (N = 7) was injected with pentoxifylline 10 minutes prior to injury. The control group (N = 5) received an identical protocol, except that this group was injected with an equal amount of saline. Results of this investigation revealed that pentoxifylline treatment significantly increased spinal cord blood flow. In the pentoxifylline-treated group, spinal cord blood flow was significantly higher from 120 to 240 minutes postinjury compared with that of the control group. We conclude that via its multiple physiologic effects, pentoxifylline significantly improves spinal cord blood flow in experimental spinal cord injury.

Animals↗
PubMed1998

Effect of hypertonic saline on leukocyte activity after spinal cord injury.

STUDY DESIGN: The effect of intravenous administration of hypertonic saline on leukocyte adhesion after compression injury of the spinal cord was evaluated. OBJECTIVES: To investigate changes in leukocyte adhesion after spinal cord injury and to evaluate the effect of hypertonic saline on this process. SUMMARY OF BACKGROUND DATA: Leukocytes have been thought to exacerbate tissue injury after ischemia-reperfusion. Downregulating and reducing the number of circulating leukocytes has attenuated tissue damage in various models of cerebral ischemia. Recently, investigators have reported that leukocytes exacerbate injury in the spinal cord after trauma. Other recent findings have indicated that hypertonic saline may play a role in decreasing leukocyte adhesion and activation. METHODS: Sprague-Dawley rats were anesthetized, and a C3-C5 laminectomy was performed. Injury was caused by 35 g of compression applied to the cord for 10 minutes. Animals were divided into three groups: sham treated, untreated, and treated. The treated animals received 7.5% hypertonic saline (5 mL/kg, intravenously) 5 minutes after the injury. Sticking leukocytes and shear rate were measured using fluorescence microscopy. RESULTS: Administration of 7.5% hypertonic saline after injury significantly decreased the number of sticking leukocytes in the venules and arterioles. Shear rate was unchanged between the groups. CONCLUSIONS: The results show that an increase in leukocyte adhesion after a compressive injury is attenuated by the administration of 7.5% hypertonic saline. The decrease in adhesion cannot be attributed to changes in the shearing forces, because no significant change was observed in the shear rate. Hypertonic saline may interfere with leukocytes directly by interfering with their ability to swell and thus may prevent activation.

Animals↗
PubMed1998

Complement depletion improves neurological function in cerebral ischemia.

The contribution of the complement system to the exacerbation of cerebral ischemia/reperfusion injury was studied by comparing a group of rats with normal complement levels to another group that was complement depleted by cobra venom factor (CVF). The magnitude of reactive hyperemia was significantly greater in the complement depleted animals. There was also better preservation of somatosensory evoked potentials (SSEPs) in the complement depleted animals. These differences were not associated with changes in leukocyte infiltration as evidenced by myeloperoxidase and Leukotriene B4 activity. These data demonstrate that depleting the complement system can improve flow and outcome following cerebral ischemia with reperfusion.

Animals↗
PubMed1997

A chronic model to simultaneously measure intracranial pressure, cerebral blood flow, and study the pial microvasculature.

In an effort to study changes in cerebral blood flow (CBF), intracranial pressure (ICP) and intracranial compliance (ICC) simultaneously, we have developed a chronic model in rats using a pial window crown with two ports. This model can also be used to study vasoreactivity of pial vessels. Female Sprague-Dawley rats weighing between 225-250 g underwent placement of cranial chamber with dual ports under pentobarbital anesthesia. To test the utility of this technique 45 groups of rats were studied. Group 1 consisted of control animals. Group 2 consisted of rats undergoing 15 min of global cerebral ischemia. Rats in group 3 were evaluated for changes in vessel diameter and ICP after adenosine injection. In group 4 leukocyte/endothelial interactions were evaluated. These groups demonstrate the ability of this model to monitor CBF, ICP, ICC and pial vessel architecture in chronic rat experiments.

Animals↗
PubMed1997

Hypertonic saline administration attenuates spinal cord injury.

BACKGROUND: This manuscript describes the results of three studies designed to test the hypothesis that the intravenous administration of hypertonic saline could help to preserve spinal cord function after injury. METHODS: A static compression model was used to injure rat spinal cords. Somatosensory evoked potentials and spinal cord blood flow changes were monitored in the acute studies. The first study compared the effects of administration of hypertonic saline with isotonic saline solutions. The second study evaluated the effect of hypertonic saline administration at 5, 15, and 60 minutes after injury. A chronic injury model was evaluated in the third study. Spontaneous voiding, neurologic function, and evidence of histologic changes were evaluated. RESULTS AND CONCLUSIONS: The administration of hypertonic saline after spinal cord injury increased blood flow and helped preserve spinal cord function in the acute models. The rate of recovery with the chronic model was significantly faster in hypertonic saline treated animals.

Acute Disease↗
PubMed1997

Intravital fluorescence microscopy: impact of light-induced phototoxicity on adhesion of fluorescently labeled leukocytes.

Alterations in leukocyte/endothelium interaction due to phototoxic effects of the fluorescent dyes acridine orange (AO) and rhodamine 6G (Rh6G) were studied by intravital microscopy using the dorsal skinfold model in awake Syrian golden hamsters. AO (0.5 mg/kg/min; constant IV infusion) and Rh6G (0.1 micromol/kg; bolus IV) were administered via an indwelling venous catheter. Five to seven arterioles (35-55 microm) and postcapillary venules (30-65 microm) were investigated in each animal. Vessels were exposed four times for 30 sec to continuous light of the appropriate excitation wavelength with a 10-15-min time interval between exposures. Animals were randomly assigned to five experimental groups (five distinct light energy levels). AO and Rh6G induced leukocyte rolling/sticking in postcapillary venules and arterioles when exposed to high light energy levels. AO, but not Rh6G, induced arteriolar vasospasm when exposed to high light energies. The potential phototoxic effect of AO and Rh6G is demonstrated, as assessed by the stimulation of leukocyte-endothelium interaction and arteriolar vasospasm in vivo. This study underscores the necessity to optimize microscopic set-ups for intravital microscopy, to reduce the excitation light energy level significantly, and to perform stringent control experiments, ruling out an artificial phototoxicity-induced stimulation of leukocyte adhesion.

Acridine Orange↗
PubMed1995

Tumor necrosis factor alpha-induced leukocyte adhesion in normal and tumor vessels: effect of tumor type, transplantation site, and host strain.

Tumor necrosis factor alpha (TNF-alpha) can lead to tumor regression when injected locally or when used in an isolated limb perfusion, and it can enhance the tumoricidal effect of various therapies. TNF-alpha can also up-regulate adhesion molecules, and thus, facilitate the binding of leukocytes to normal vessels. The present study was designed to investigate the extent to which the host leukocytes roll and adhere to vessels of different tumors (MCaIV, a murine mammary adenocarcinoma; HGL21, a human malignant astrocytoma) at a given site or to the same tumor at different sites (dorsal skin and cranium), in different mouse strains [C3H and severe combined immunodeficient (SCID)], both with and without TNF-alpha-activation. There was no significant difference in hemodynamic parameters such as RBC velocity, diameter, or shear rate between PBS-treated control groups and corresponding TNF-alpha-treated groups. Under PBS control conditions, the leukocyte rolling count in MCaIV tumor vessels in the dorsal chamber in C3H and SCID mice and in the cranial window in C3H mice was significantly lower than that in normal vessels (P < 0.05), but stable cell adhesion was similar between normal and tumor vessels. TNF-alpha led to an increase (P < 0.05) in leukocyte-endothelial interaction in vessels in the following cases: normal tissue regardless of sites and strains, MCaIV tumor in the cranial window in C3H mice, and HGL21 tumor in the cranial window in SCID mice. However, the increase in rolling and adhesion in the MCaIV tumor in response to TNF-alpha was significantly lower than in the corresponding normal vessels (P < 0.05) in the dorsal chamber in C3H and SCID mice and in the cranial window in C3H mice. The HGL21 tumor in the cranial window in SCID mice showed leukocyte rolling and adhesion comparable to that in normal pial vessels. These findings suggest that (a) in general, basal leukocyte rolling is lower in tumor vessels than in normal vessels; (b) leukocyte rolling and adhesion in tumors can be enhanced by TNF-alpha-mediated activation; and (c) the TNF-alpha response is dependent on tumor type, transplantation site, and host strain. These results have significant implications in the gene therapy of cancer using TNF-alpha-gene-transfected cancer cells or lymphocytes.

Animals↗
PubMed1994

Vascular permeability and microcirculation of gliomas and mammary carcinomas transplanted in rat and mouse cranial windows.

Many brain tumors are highly resistant to chemotherapy, presumably due to the presence of a tight blood-tumor barrier. For a better understanding of the regulation of this barrier by the brain environment, a new intravital microscopy model was established by transplanting tumor tissue into cranial windows in both rats and mice. The model was characterized by RBC velocities, vessel diameters, and vascular permeabilities of various tumors: R3230AC (a rat mammary adenocarcinoma), MCaIV (a mouse mammary adenocarcinoma), and U87 and HGL21 (human malignant astrocytomas). Our results showed that tumor blood flow in cranial windows was one to three orders of magnitude lower than the blood flow in pial vessels and similar to that in dorsal skin-fold chambers observed in previous studies. The mean vessel diameter ranged from 6.8 +/- 1.3 microns for HGL21 to 30.4 +/- 8.5 microns for MCaIV. At least one order of magnitude difference in vascular permeability to albumin was observed between tumor lines: 0.11 +/- 0.05 x 10(-7) cm/s for HGL21 versus 3.8 +/- 1.2 x 10(-7) cm/s for U87. The low vascular permeability of HGL21, which was also confirmed by both sodium fluorescein and Lissamine green injections, suggests that not all tumors are leaky to tracer molecules and that the blood-tumor barrier of this tumor still possesses some characteristics of blood-brain barrier as observed in other intracranial tumors. The model presented here will allow us to manipulate the vascular permeability in brain tumors and thus may provide new information on the regulation of the blood-tumor barrier and new strategies for improving drug delivery in brain tumors.

Animals↗
PubMed1994

Leukocyte involvement in cerebral infarct generation after ischemia and reperfusion.

White blood cell involvement in the generation of cerebral infarcts was evaluated following ischemia and reperfusion injury in the rat. Control and leukopenic rats (induced by vinblastine, WBC counts < 1500/mm3) were compared in a global forebrain ischemic model after 1 h of ischemia and 1 h 15 min of reperfusion. Cerebral infarcts were defined on coronal brain sections using Triphenyl tetrazolium chloride (TTC) staining. Electroencephalographic activity (EEG) and somatosensory evoked potentials (SSEP) were also compared. Results indicate that the area infarcted in leukopenic rats was significantly less than infarcts generated in corresponding controls (21 +/- 16% vs. 70 +/- 16%). In addition, EEG was preserved in all leukopenic animals when compared to controls, both during ischemia and after reperfusion. The cortical peak component of the SSEP was also better preserved in the leukopenic animals both during ischemia and at 60 min of reperfusion. These results indicate white blood cell participation in the generation of cerebral damage in a model of global forebrain ischemia and reperfusion as indicated by TTC staining of cerebral infarcts.

Animals↗
PubMed1994

Preservation of post-compression spinal cord function by infusion of hypertonic saline.

We tested the hypothesis that the administration of hypertonic saline, following traumatic injury to the spinal cord, could enhance blood flow to the cord and preserve function. Rats were used as the experimental model. Direct compression of the spinal cord for a period of 10 min was done to produce the injury. Somatosensory evoked potentials (SSEPs) and spinal cord blood flow were measured using a laser Doppler flow meter throughout the experiment. Comparisons of the blood flow values and SSEPs were made among four different groups of animals. The control group received no fluid resuscitation after injury. A second group received a bolus injection of isotonic saline (0.5 ml/100 g) as an i.v. infusion over a period of 1 min. A third group received a bolus infusion of 7.5% NaCl (0.5 ml/100 g) over a period of 1 min. The final group received 4 ml/100 g of 0.9% NaCl over a period of 10 min. The administration of hypertonic saline significantly reduced spinal cord vascular resistance during the first 10 min after infusion. During the first 30 min after the removal of compression, spinal cord blood flow was greater in the hypertonic saline group than in the other three groups. The hypertonic saline group had a reactive hyperemia whereas the flow in the other groups remained at or below control values. Beginning 10 min after injury and for the remainder of the 1-h observation period, the latency of the cortical peak of the SSEP in the group receiving hypertonic saline was significantly shorter than in any of the other three groups. These results indicate that the administration of hypertonic saline enhances blood flow and preserves spinal cord conduction following traumatic injury to the spinal cord.

Animals↗
PubMed1992

Age-related alterations in the arterial microvasculature of skeletal muscle.

This study investigated the possibility that the aging process results in alterations in the structure and/or functional reactivity of the microvessels that could contribute to increased resistance to blood flow in working skeletal muscle. Initially, latex casts were made of the cremaster muscle microvasculature in adult (12 mo) and senescent (24 mo) male Fischer 344 rats. Although the average diameter was not different between age groups, segmental length (distance between adjacent branches) increased significantly (3rd order) during aging. Additionally, in vivo experiments were performed to determine the response of the vessels to the topical application of norepinephrine and adenosine. There was no increase in vasoconstriction produced by norepinephrine; however, the vasodilation in response to adenosine declined dramatically (1st and 2nd order) with advancing age. It can be concluded that the increase in skeletal muscle vascular resistance during contraction in aged male rats could be explained by morphological changes and/or the diminished vasodilation elicited by adenosine.

Adenosine↗
PubMed1991

Effect of ultrasound on regional cerebral blood flow in neonatal rats.

By employing a laser-Doppler flowmeter, an investigation was performed to determine whether ultrasound causes a change in regional cerebral blood flow (rCBF). rCBF in neonatal rats (age: 2-6 days postgestation) was measured before, during, and after exposure of both cerebral hemispheres to continuous-wave ultrasound (1.0 MHz) at an intensity of 2.0 W/cm2 (SATA) for a period of 5 min. After 3 min of ultrasound treatment, there was a statistically significant augmentation in rCBF (p less than 0.05) with rCBF increasing by a factor of 2.7 +/- 0.4 (mean +/- SEM) after 5 min of ultrasound. This response was demonstrated to be a transient effect, because rCBF returned to its original value 4-6 min after termination of the ultrasound treatment.

Animals↗
PubMed1991

Influence of nitrous oxide administration and discontinuation thereof on blood flow in cerebral cortex, cerebellum and brain stem in the rat.

The effect of nitrous oxide on blood flow in the cerebral cortex, the cerebellum and the brain stem was evaluated in a rat model. Catheters were surgically implanted in advance to avoid influence from other anaesthetics. The animals were housed in a plastic tube where they were allowed to breathe spontaneously. Blood flow was determined with a microsphere technique. Animals were exposed to nitrous oxide, 75-80%, for 45 min and blood flow was measured after 15 and 45 min exposure and was compared to values obtained during room air breathing. In one animal group, nitrous oxide was administered for 45 min and blood flows were measured after 5 and 30 min withdrawal of the gas. Results showed that all animals had significant hyperventilation. In three groups CO2 had to be added to inspiratory gases to normalize arterial blood gases. This was interpreted as caused by stressful experimental conditions, not blunted by the nitrous oxide. Cortical blood flow values in the control situation were also higher than obtained in other animal studies. Despite this, nitrous oxide showed a significant vasodilation in the cerebral cortex and the brain stem at 15 min exposure. At discontinuation of nitrous oxide administration, blood flow values had decreased at 5 min.

Animals↗
PubMed1990

Leukocyte involvement in cerebral ischemia and reperfusion injury.

Leukocytes have been postulated to contribute to cerebral ischemia and reperfusion injury. The present study implies that leukocytes have a deleterious effect in the brain following ischemia. We compared the alteration of cortical electrical activity following transient, incomplete cerebral ischemia in control and leukopenic rats by monitoring somatosensory evoked potentials and electroencephalographic activity. There was complete cessation of electroencephalographic activity, and the cortical peak of the evoked potential was abolished during ischemia in the control animals. However, when the animals were rendered leukopenic, there was maintenance of electroencephalographic activity with reduced amplitude and preservation of the cortical peak of the evoked response during the ischemic period. This indicates that when the animals are made leukopenic, even under ischemic conditions, the neurophysiologic functioning is still maintained to a certain extent.

Animals↗
PubMed1989

Inhibition of platelet hemostatic plug formation by trigramin, a novel RGD-peptide.

Trigramin, a cysteine rich, RGD (Arg-Gly-Asp)-containing peptide from Trimeresurus gramineus snake venom (Mr 7,500) has been previously reported to inhibit fibrinogen binding to ADP-activated platelets and platelet aggregation (disassociation constant 10(-8) M). The present study demonstrates that the infusion of trigramin (17-212 micrograms/100 g body wt) significantly prolonged the bleeding time of severed mesenteric arteries in hamsters (anesthetized with 65 mg/kg pentobarbital), whereas the infusion of RGDS (Arg-Gly-Asp-Ser, 0.45-1.0 mg/100 g body wt) failed to increase the bleeding time in this model. The bleeding time immediately returned to normal after cessation of trigramin infusion. The pattern of the disappearance of 125I-labeled trigramin from the circulation fit a two-compartment model with the half-life for the fast component between 0.7 and 2.0 min and with the half-life for the slow component between 31 and 105 min. It appeared that the kidney and liver are major routes of elimination of trigramin from the circulation. The ability of trigramin to prolong bleeding time, as well as its rapid disappearance from the circulation, indicates that this peptide may be a useful compound to transiently prevent the ability of platelets to form thromboemboli without impairing their long-term hemostatic function.

Animals↗