Biomedical subjects

J Marsala

Publications and source records attributed to J Marsala.

At least 55 records · Page 3Linked to original sources

PubMed1995

Effects of stobadine on survival, histopathologic outcome and acid-base status after global brain ischemia in dogs.

Present study is designed to examine an effect of Stobadine, a new cell-protective agent with antiarrhythmic properties, on survival, electron microscopic changes in microvasculatory bed of selected brain areas and acid-base parameters of arterial blood after global brain ischemia and reperfusion. Forty dogs (weighting 6 to 15 kg) were anesthetized using pentobarbital i.v. (5%, 35 mg/kg). An intubation and controlled ventilation was performed. One catheter was placed into v. femoralis (for drug administration), another to a. femoralis (for blood samples) and third one into the left common carotid artery (continuous brain blood feeding pressure measurement). Each dog underwent an surgical obstruction of principal brain-supplying arteries and immediate administration of hypotensive agent (Arfonad, 0.062%) resulting in 7 minutes lasting global brain ischemia (brain feeding pressure 1.0-1.5 kPa). If survived, animals were killed at one (perfusion-fixed for electron microscopy) or three days after ischemia. Ultrastructural changes were evaluated at 24 hour of recirculation (control and S2 groups only). Vehicle or 1, 2 or 5 mg/kg of Stobadine (group S1, S2, S5 resp.) i.v. was given 30 minutes prior to ischemia. Significantly longer survival was observed in group S2 (8 of 11 until 72 hour) as compared to control group (none of 7, p < 0.005 by Student's t-test). The ultrastructural changes of blood-brain barrier structures were none or minimal in S2 (single damage type), but in control group three major types of capillary damages has appeared at 24 hour after insult. They include intravascular coagulopathy (type I), no-reflow (type II) phenomenon with astrocyte edema, and capillary necrosis (type III) finally. Stobadine pretreated animals experienced hypercapnia, elevated arterial O2 and slight deeper acidemia (depending on dosage) as compared to control group. Respiratory compensation of metabolic acidosis was present in control group, but lacking in all stobadine pretreated animals. Stobadine at 2 mg/kg improves survival (Student p < 0.005, Mantel-Cox p < 0.05, Fischer p = 0.004). Stobadine has a protective effect on neurons and structures of blood-brain barrier (endothel, astrocytes, basement membrane) seen in electron microscope.

Acid-Base Equilibrium↗

PubMed1995

Graded postischemic reoxygenation attenuates ischemia-reperfusion-induced nuclear and nucleolar damage in lumbosacral dorsal root ganglia neurons. A light and electron microscopic study in rabbit.

Ischemia and reperfusion-induced nuclear and nucleolar changes of the lumbosacral dorsal root ganglia neurons were studied in a spinal cord ischemic model of a rabbit. Twenty and forty min abdominal aorta ligation followed immediately by perfusion fixation, 20 min abdominal aorta ligation followed by 1 h of normoxic reoxygenation and 20 min abdominal aorta ligation followed by 1 h of graded postischemic reoxygenation were tested. In animals subjected only to a 20 and 40 min aorta ligation irregularly undulated nuclear membrane and occurrence of dark osmiophilic dense clumps often located close to interchromatin granules were found. The segregation of the nucleolar granular and fibrillar components became apparent but fibrillar centers were almost completely absent. In animals subjected to 20 min ligation followed by 1 h of normoxic reoxygenation a high number of dense clumps, loosely disseminated throughout the nucleoplasm was detected along with almost complete fragmentation and segregation of the nucleolus. The application of the graded postischemic reoxygenation has proven effective as a neuroprotective and antisegregatory adjunct whereby the nucleolar fibrillar and granular components regained almost normal appearance, and the occurrence of dense intranuclear clumps was greatly reduced.

Animals↗

PubMed1995

Formation of filamentous and multivesicular bodies after intrathecal MK-801 injection.

Our study of ultrastructural changes in lumbar spinal cord is based on the rats permanent intrathecal (IT) catheter model of MK-801 injection. After 3 days survival with the IT catheter the animals were treated by injection of MK-801 or saline. Five hrs post-treatment the rats were transcardially perfused with 4% paraformaldehyde in 0.1 M PB. L4-5 segments of the spinal cord were dissected and processed for EM. The presence of single or multiple filamentous/multivesicular bodies in neuronal cytoplasm of MK-801 treated animals was apparent.

Animals↗

PubMed1995

[Selective vulnerability of neuronal injury after experimental heart arrest].

The study was aimed at the analysis of vulnerability of the olfactory bulb neurons in dogs after experimental heart arrest lasting for 15 minutes and recirculation lasting for 1 hour. By means of the Nauta degenerative neurohistologic method the reactions of individual types of nerve cells in the olfactory bulb were investigated. Nauta-positive granules were observed in the cytoplasm of the mitral and tufted cells of the olfactory bulb, which are of dopaminergic character. The granulations were present in the cellular areas which are rich in Nissl substance. The granular and short-axon cells of GABA-ergic character which contain a small amount of Nissl granules lack the Nauta-positive granules. Similarly, the Nauta-positive granules were absent in the axon hillock of mitral cells which under normal conditions do not contain the Nissl substance. These results justify the conclusion that ischemia lasting for 15 minutes and one-hour recirculation primarily affect the excitatory neurons rich in the Nissl substance. (Fig. 4, Ref. 16.).

Animals↗

PubMed1994

Ischemia-induced delayed-onset paraplegia is accompanied by an unusual form of synaptic degeneration in the lumbosacral segments: an experimental light and electron microscopic study in dogs.

We studied the effect of high thoracic aorta cross-clamping, complete transverse section of the spinal cord at Th6 level, and combined hemisection at Th6 level followed later by high thoracic aorta cross-clamping upon the morphology and number of identified presynaptic knobs in lumbosacral segments in dogs. In animals surviving 48-72 hours after high thoracic aorta cross-clamping the occurrence of an unusual form of boutons accompanied by periboutonal halo in L3-S1 segments was found. According to the bouton size and light as well as electron microscopic appearance, four types, i.e., light giant (T1), dark enlarged (T2), light giant with periboutonal halo (T3), and giant disintegrating (T4) boutons were detected after 48 and 72 hour reperfusion. The appearance of four boutonal types in the lumbosacral segments is caused by spinal cord ischemia secondary to high thoracic aorta cross-clamping followed by 48 or 72 hour reperfusion. At the end of the sixth reperfusion day no signs of enlarged and giant boutons were detected in L3-S1 segments. A statistically significant increase of enlarged and giant boutons was noted at the end of the third reperfusion day in comparison with 48 hour survival. After spinal cord transection at midthoracic (Th6) level, followed by 72 hour survival, no such unusual synaptic knobs could be found in L3-S1 segments. The laminar distribution pattern of T1-T4 types based on light microscopic analysis and confirmed electron microscopically is characteristic and strictly bound to those spinal cord gray matter layers which serve as main termination sites of the descending cortical, brain stem, as well as long propriospinal projections in the lumbosacral segments (laminae V-VII). A statistically significant increase of enlarged and giant boutons was found in the intermediate zone (lamina VII). Hemisection at midthoracic level (Th6) followed later by 30 minute high thoracic aorta cross-clamping and 48 hour reperfusion caused a marked decrease of enlarged and giant boutons in L3-S1 segments on the hemisectioned side in comparison with the contralateral one. Large amounts of irregularly arranged round vesicles and tubular profiles were disclosed in the boutonal matrix of T1, T3, and T4 types in L3-S1 segments of animals subjected to 30 minute high thoracic aorta cross-clamping followed by 72 hour reperfusion. Accumulation of tubular and membranous materials was invariably seen in the bulbous enlargement of the terminal axonal branch.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

Influence of graded postischemic reoxygenation on reperfusion alterations in rabbit dorsal root ganglion neurons.

Ultrastructural postischemic changes in the rabbit dorsal root ganglion (DRG) neurons were studied after 20 min infrarenal aortic occlusion followed by normoxic or graded postischemic reoxygenation (GPIR) with survival times ranging from 1 to 4 days. After normoxic reoxygenation with 1 day survival, in A-type neurons a dispersal of Nissl bodies and nuclear changes characterized by crenated nuclear membrane, chromatin condensation and increased density of karyoplasm were observed. After 2 days of reperfusion, alterations of B-type neurons became more pronounced. Their nuclei contained numerous myelinoid bodies and the nucleoli showed an apparent sequestration of the nucleolonema. At 4 days postischemia, degenerating extensively vacuolated B-cells were frequently seen. Graded reoxygenation achieved by the blood pO2 hypotension and its gradual increase during early reperfusion phase (30 min) had a significant neuroprotective effect, as indicated by morphological and quantitative analysis showing a good preservation of cytoplasmic and nuclear structures in both types of neurons which were evident even 4 days postischemia. The changes are discussed in relation with the effect of tissue hyperoxia during early reperfusion and its involvement in the development of ischemic neuronal injury.

Animals↗

PubMed1993

Panmyelic epidural cooling protects against ischemic spinal cord damage.

The neuroprotective effect of epidural cooling before and during spinal cord ischemia on the neurological, neurophysiological, and histopathological outcome was evaluated after 40 min of proximal and distal thoracic aorta crossclamping in dogs. In the normothermic group (n = 12), no attempt was made to change the spinal cord temperature. Four of eight animals showed complete paraplegia and four had partial recovery. The N3 component of spinal somatosensory-evoked potentials recovered to only 11.7 +/- 1.4% after 2 hr of recirculation and to 45% of control value after 2 days of survival. In the transverse sections taken from L1-L7 segments, apparent interneuronal damage in the intermediate zone was found after 2 hr of reperfusion followed by a heavy loss of interneurons after 2 days of survival and functionally defined as fully developed paraplegia. In the hypothermic group (n = 12), the spinal cord temperature was lowered 3 min before aortic crossclamping with a bolus of epidurally administered 0.9 N saline solution (8 ml/kg at 5 degrees C) to 28.5 +/- 1.3 degrees C and was maintained throughout the crossclamping time with the additional infusion of the same solution (20 ml/kg/40 min) using a peristaltic pump. Seven of eight animals had no neurological deficit and one animal showed partial recovery, which was significantly better than the motor score for the normothermic group (P < 0.05). The SSEP revealed 55% of postsynaptic (N3) wave recovery after 2 hr of recirculation and 92% recovery after 2 days survival, which was significantly higher than those for the normothermic animals (P < 0.05). Histological analysis showed almost full protection of interneurons and A-motoneurons verified after 2 hr and 2 days, respectively. We conclude that spinal cord epidural cooling has a highly protective effect against ischemic spinal cord damage under experimental conditions of high thoracic aorta crossclamping in dogs.

Animals↗

PubMed1993

Cholinergic enzymes in spinal cord infarction. Biochemical and histochemical changes.

Activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) were studied in the ventral and dorsal horns and the intermediate zone of the rabbit lumbar spinal cord (L4-7) 24 and 96 h after ischemia caused by 20 or 40 min occlusion of the abdominal aorta. Changes of AChE and butyrylcholinesterase (BChE) activities were also detected histochemically by the direct thiocholine method. No significant changes were found immediately after ischemia. The most remarkable change after 20 min ischemia and 1 or 4 d of reperfusion was heterogeneous decrease in ChAT and AChE activities in the examined parts of gray matter. The highest loss of enzyme activities was found in the ventral horns and the lowest in dorsal horns. Following 40 min ischemia and reperfusion the significant depletion in enzyme activities in all investigated zones of the gray matter was accompanied with necrotic degenerative changes. There was a relatively greater decrease in ChAT and AChE activities in the ventral horns that corresponded with a more prominent morphological damage of the cholinergic neurons in this zone of the spinal cord.

Acetylcholinesterase↗

PubMed1993

Epidural perfusion cooling protection against protracted spinal cord ischemia in rabbits.

The protective effect of a modified epidural cooling technique was assessed in a rabbit spinal cord ischemia model. The epidural space around the lumbar segments with induced ischemia was continually perfused with cold (5 degrees C) isotonic saline via two communicating spinal canal openings. This procedure allowed the spinal cord to be kept deeply hypothermic (< 15 degrees C within central gray matter) during the ischemic period. The animals were subjected to either normothermic ischemia (Group A) or hypothermic ischemia (Group B). Each group contained three subgroups of animals undergoing 20, 40, or 60 minutes of aortic ligation. Their neurological outcomes were evaluated up to 48 hours postischemia, and the intergroup differences were compared. Two days postischemia, all of the animals were sacrificed by transcardial perfusion-fixation and their lumbar segments were processed for histopathological examination. In addition, in animals with 60-minute ischemia, spinal somatosensory evoked potentials were recorded during surgical intervention and again after 48 hours. In the normothermic animals, a high incidence of paraplegia was detected: in 40% after 20 minutes of ischemia, in 75% after 40 minutes, and in 100% after 60 minutes. In contrast, all of the hypothermic animals exhibited full neurological recovery even after 60 minutes of ischemia. Both electrophysiological and histological observations clearly correlated with the neurological findings. The results suggest that deep spinal cord hypothermia produced by epidural perfusion cooling provides effective protection against protracted spinal cord ischemia in rabbits.

Animals↗

PubMed1993

Unusual type of ischemically induced synaptic degeneration studied by Hicks method.

This study describes the degenerating axonal termination and filamentous synaptic degeneration after 30 minutes spinal cord ischemia followed by 3 days survival using Hicks neurofibrillar impregnation. From laminoarchitectonic point of view a clear evidence was gained supporting the original description obtained by Nauta method. The majority of degenerated boutons revealed by Hicks method was found in the deep layers of the dorsal horn and then with increasing density in the intermediate zone and partly in the neuropil of the anterior horn. These results confirm the ability of Hicks method as a reliable tool in systematic research of the ischemically damaged synaptic contacts.

Animals↗

PubMed1993

A new applicability of the suppressive Nauta method in the early phase of neuronal damage.

A new applicability of the suppressive Nauta impregnation method was tested allowing the detailed mapping of early neuronal damage expressed in the form of somatodendritic argyrophilia. Two spinal cord ischemia-reperfusion models of rabbit and dog, a model of canine global brain ischemia-reperfusion, involving cardiac arrest followed by resuscitation, and a canine spinal cord compression-decompression model were used. Early phases of neuronal damage are characterized by conspicuous somatodendritic argyrophilia permitting an exact evaluation of acute neuronal damage according to soma size, dendritic ramifications and localization of the affected neuronal neuronal pool. By its high sensitivity to somatodendritic damage the suppressive Nauta method appears to be a valuable neuropathological technique.

Animals↗

PubMed1992

Post cardiac arrest hyperoxic resuscitation enhances neuronal vulnerability of the respiratory rhythm generator and some brainstem and spinal cord neuronal pools in the dog.

Selective neuronal vulnerability of the motor cortex, basal ganglia, brainstem, medulla, cerebellum, C6 and L6 segments of the spinal cord were studied after 15 min of cardiac arrest followed by 1 h of normoxic or hyperoxic resuscitation using the suppressive Nauta method in dogs. Hyperoxic resuscitation causes characteristic somatodendritic argyrophilia of the interneuronal pool in the spinal cord and lower medulla. Cuneate, lateral reticular, supraspinal, and caudal trigeminal nuclei as well as the dorsal and ventral respiratory neuronal groups were heavily involved. Similarly, the Purkinje cells, neurons in the middle and deep portions of the mesencephalic tectum, perirubral, pretectal, posterior commissure, middle-sized striatal and giant pyramidal (Betz's) neurons in the motor cortex became argyrophilic. Hyperoxic resuscitation versus normoxic resuscitation causes statistically significant somatodendritic argyrophilia of the dorsal respiratory group, cuneate, dorsal lateral geniculate and thalamic reticular nuclei.

Animals↗

PubMed1992

Graded postischemic reoxygenation reduces lipid peroxidation and reperfusion injury in the rabbit spinal cord.

The effect of graded postischemic reoxygenation on lipid peroxidation, neurological recovery and the degree of spinal cord damage after 20 min abdominal aorta ligature was tested in the rabbit. In comparison with normoxic recirculation, the graded postischemic reoxygenation (GPIR) during early phase of reperfusion (30 min) significantly reduced the level of lipid peroxidation products (LPP) in vivo and in vitro after 1 h survival. Neuropathological changes in animals with normoxic reperfusion showed gradual deterioration ranging from appearance of heavy argyrophilic neurons after 1 h reperfusion followed by neuronal necroses after 12 h survival to the development of an extensive spongy lesion reaching ventral horn and intermediate zone 2 days postoperatively. The neuroprotective effect of graded postischemic reoxygenation was evident even after 2 days survival with preserved structural integrity of the gray matter as confirmed by light and electron microscopy. The results indicate that graded postischemic reoxygenation during 1 h reperfusion can reduce lipid peroxidation and suppress irreversible neuronal damage using developing during the early reperfusion phase.

Animals↗

PubMed1992

Prolonged postischemic hyperventilation reduces acute neuronal damage after 15 min of cardiac arrest in the dog.

Hyperventilation is commonly used as a constituent of antiedematous therapy after global cerebral ischemia. The effect of hyperventilation on brain functions, however, is complex, and a number of mechanisms involved remains unclear. In this study, we attempted to determine whether postischemic hyperventilation influences acute neuronal changes developing during recirculation. Two groups of dogs underwent 15 min of cardiac arrest and cardiopulmonary resuscitation with an 8 h survival. After resuscitation, in group A the internal environment was maintained in the physiological ranges. In group B the animals were artificially hyperventilated maintaining a high level of respiratory alkalosis during recirculation. Histopathological examination of the vulnerable structures was performed using the Nauta degenerating method and the argyrophilic neurons were counted. Statistically significant amelioration in group B suggests that postischemic hyperventilation may act as a neuroprotective factor.

Animals↗

PubMed1992

Silver impregnability of ischemia-sensitive neocortical neurons after 15 minutes of cardiac arrest in the dog.

The development of postischemic neuronal argyrophilia and the subsequent fate of argyrophilic neurons were studied in dogs after 15 min of complete cerebral ischemia and survival varying from 1 h to 7 days. Histopathological examination of the vulnerable neocortical region was performed using the Nauta degeneration method, and the time course of cellular changes was described. Clear-cut neuronal argyrophilia was found to precede cell body shrinkage and gradual disintegration corresponding to selective neuronal death. To clarify this initial stage of neuronal impregnability, the samples from the animals surviving 8 h postarrest were stained with toluidine blue or processed for electron microscopy, and the distribution of argyrophilic cells was confirmed to be identical with that of hyperchromatic or electron-dense cells. On the other hand, infrequently observed "tissue infarctions" exhibited no silver affinity in spite of apparent cellular damage. These findings indicate that enhanced impregnability is related to cytochemical processes incidental to the phenomenon of "selective neuronal death", which can be readily detected by the Nauta method.

Animals↗

PubMed1992

Effect of liposomes on lipid peroxidation and total phospholipids in rabbit ischemic spinal cord model.

The effect of spinal cord ischemia (induced by abdominal aorta ligation for 20 minutes) on lipid peroxidation and TPL composition was investigated and discussed in our previous articles. It is known, that partially reduced species of oxygen can be formed under aerobic conditions. For that reason, the effect of ligation release for 60 minutes was observed in experimental animals treated with the selected liposomes. Administration of CP, (CP+SA) and (CP+Chol) liposomes applied 30 minutes before 20 minutes ischemia revealed an ameliorating effect on in vivo and in vitro Fe-dependent peroxidation manifested by TBA-RS accumulation. Combined use of (CP+SA) liposomes with lipophylic form of stobadine (DP 1031) was not more effective. Application of CP liposomes directly before the ligation release slightly increased the antiradical capacity in spinal cord homogenates comparing with not-treated animals. Accumulation of TBA-RS was accompanied by TPL degradation during recirculation period but values of TPL after liposomal treatment were unaffected.

Animals↗

PubMed1992

[Neurotransplantation, critical analysis and perspectives].

Basic morphological and functional properties of basal ganglia are described and their role in the development of Parkinson's disease is discussed in detail. Based on recent experimental data, the problem of human autologous adrenal medulla transplants as well as human dopaminergic neurons is analyzed and prospective approaches to successful therapeutic interventions are considered mainly from the molecular and immunobiological point of view. The relative limitations of the regenerative capacity and transplantability of the nervous tissue are assessed and compared with the critical developmental periods of human neurogenesis (Fig. 6, Ref. 47.).

Adrenal Medulla↗

PubMed1991

The blood-brain barrier permeability in graded postischemic spinal cord reoxygenation in rabbits.

Postischemic blood-brain barrier permeability changes were studied using a rabbit spinal cord ischemia model followed by normoxic recirculation (group I) or graded postischemic reoxygenation (group II). No signs of Evans blue leakage were found in lumbar segments 3 h after normoxic blood recirculation. After 6 h, the fluorescence was apparent in the perivascular space and in the pericytes, followed by a massive penetration of the tracer into the neuropil and perikarya at 12 h survival; 18 h after normoxic reperfusion, the fluorescence was localized in the cytoplasm of the middle-sized and large neurons. Graded postischemic reoxygenation of lumbar segments applied during the same survival periods had a highly protective effect on vascular membrane permeability. The structural components of the vascular wall as well as neuropil and perikarya remained after its application entirely tracer free.

Animals↗