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Biomedical subjects

I Klatzo

Publications and source records attributed to I Klatzo.

At least 37 records · Page 2Linked to original sources
PubMed1989

Preservation of GABAergic perikarya and boutons after transient ischemia in the gerbil hippocampal CA1 field.

Using an antibody directed against the gamma-aminobutyric acid (GABA)-synthetizing enzyme glutamate decarboxylase (GAD) the fate of the GABAergic innervation was investigated in the hippocampal field CA1 of gerbils up to 14 days after a bilateral transient 5-min occlusion of carotid arteries. As described previously, the CA1 pyramidal cells were subject to the ischemia-induced delayed neuronal death, the first signs of which were detectable after 2 days and which was fully developed after 4 days. Local GAD-immunoreactive neurons and boutons, however, exhibited no changes in their distribution and morphology over the whole 14-day period investigated, as studied both at the light and electron microscopic level. Thus, it can be assumed that the increased excitation observed during the development of delayed neuronal death, is not due to a loss of GABAergic neuronal profiles. The resistance of the GABAergic neurons to the ischemic insult is discussed in relation to the presence of Ca2+-binding proteins in this class of neurons, and the long persistence of innervation in an area nearly devoid of postsynaptic targets is considered.

Animals↗
PubMed1989

Effect of acute electrode placement on regional CBF in the gerbil: a comparison of blood flow measured by hydrogen clearance, [3H]nicotine, and [14C]iodoantipyrine techniques.

Regional cerebral blood flow (rCBF) was compared in the gerbil by means of [3H]nicotine, [14C]-iodoantipyrine, and hydrogen clearance techniques. In agreement with other studies, nicotine and iodoantipyrine methods gave virtually identical results. With these methods, it was observed that a reduction in blood flow occurred shortly after insertion of an electrode into the striatum for hydrogen clearance measurement, affecting rCBF throughout the impaled hemisphere. The reduction was moderate (30%) in the striatum and hippocampus, but much greater (70%) in cortical regions. Identical deficits were observed following brief penetrations involving only cortex. Following chronic electrode placement in the striatum, regional blood flow values obtained with [3H]nicotine returned to the control range within 6 h. Blood flow estimates obtained in the striatum with the implanted electrode increased with a similar time course, so that by 6-24 h, hydrogen clearance gave values indistinguishable from control values obtained with [3H]nicotine. These results clearly demonstrate that reduction of CBF subsequent to electrode placement can account for the low values frequently obtained with the hydrogen clearance method in small animals. The distribution of the deficit and the time course of its recovery are similar to blood flow changes associated with spreading depression. While mechanisms responsible for this effect remain to be fully identified, chronic implantation is a practical solution that allows the continued use of hydrogen clearance as a convenient method for repeated measurement of blood flow in the same animal.

Animals↗
PubMed1989

Cerebral vascular volume after repeated ischemic insults in the gerbil: comparison with changes in CBF and brain edema.

The time course of changes in cerebral intravascular volume was evaluated during 24 h following a series of three 5-min carotid artery occlusions spaced at 1-h intervals and compared with the changes occurring after single 5- or 15-min occlusions. Quantitative estimates of cerebral red cell volume, plasma volume, and total blood volume were obtained from the distribution spaces of 51Cr-labeled erythrocytes and 125I-albumin infused prior to killing at varied recirculation intervals. Significant reductions in vascular volume occurred in all ischemic brain regions within 1 h following a single 5-min occlusion, which recovered to control values within 6 h. A similar time course was seen after repeated occlusions. The reductions in volume remained significant at 6 h after a single 15-min occlusion, but there was no difference from control by 24 h. Thus, the time course of total vascular volume correlates well with that of CBF changes previously described, and both blood flow and blood volume are at normal levels during the time of severe edema 24 h after repeated occlusions. Calculated cerebral hematocrit was 60-70% of that obtained from the femoral artery, but was identical in all brain regions and was constant throughout the postischemic recirculation period, with the exception of a transient reduction in both peripheral and cerebral hematocrit observed at 6-h recirculation following single 15-min occlusions. These results suggest that changes in CBF and blood volume reflect primarily the status of larger vessels and that values in the normal range may be observed even under conditions of severe edema and impaired perfusion at the capillary level.

Animals↗
PubMed1989

Role of cerebral endothelium in brain oedema.

The view that cerebral endothelial cells represent the cellular basis of the blood-brain barrier has been generally accepted. The regulation of transport processes operating in the cerebral endothelial cells is currently of great interest. Our knowledge of these regulatory mechanisms is briefly reviewed here with special regard to the molecular processes involved in the formation of brain oedema and emphasis on new therapeutic means for its prevention.

Brain↗
PubMed1989

Observations on cerebral ischaemia in cats at injury threshold levels.

The potential for recovery of brain tissue subjected to ischaemia at a threshold level of injury was evaluated in cats subjected to 20 min middle cerebral artery occlusion. In addition to assessment of regional cerebral blood flow and water content, the permeability of the bloodbrain barrier and morphological changes detected by light microscopy were studied at various time intervals. Our observations revealed that although a similar reduction of blood flow during arterial occlusion was found both in the caudate nucleus and the cerebral cortex, the reactive hyperaemia was consistently higher in the caudate nucleus than in the cortex. After 24 h the caudate nucleus also revealed a significantly higher water content and increased vascular permeability than the cortex. Morphological observations at 24 h in areas affected by ischaemia showed widespread, marked ischaemic neuronal injury, whereas at 3 d there was, in addition, a vigorous proliferative reaction of vascular elements. Cats sacrificed at 14 d revealed a remarkably good preservation of neurons, both in the caudate nucleus and cortex which otherwise showed a few circumscribed, small, infarcts surrounded by normal nerve cells. Our study suggests that neurons injured at threshold level have a considerable capacity for recovery. Otherwise, with a similar degree of ischaemia, the caudate nucleus appears more prone to increased vascular permeability and oedema than the cerebral cortex.

Animals↗
PubMed1988

Microvascular disturbances and edema formation after repetitive ischemia of gerbil brain.

Three transient episodes of 5 min ischemia spaced at 1-h intervals were produced in Mongolian gerbils by bilateral carotid artery occlusion with an implanted vascular occlusion device. The interval of 1 h was chosen to allow for the development of post-ischemic hypoperfusion between the ischemic episodes. Three minutes and 1 h after each ischemic episode, and 6 and 24 h after the third occlusion, Evan's blue (EB) was injected intravenously to trace circulating blood, and the number of perfused capillaries was determined in various brain regions by fluorescence microscopy. Brain edema was evaluated by measuring specific gravity in tissue samples taken from adjacent areas. Repetitive ischemia caused progressively increasing brain edema and a progressive reduction of the number of perfused capillaries. Immediately after each ischemic episode, transient recruitment of capillaries occurred, thus excluding no-reflow as a main pathogenetic factor of microcirculatory disturbances. The pattern of microcirculation 6 and 24 h after the last occlusion revealed a redistribution of circulating blood, characterized by a reduction in the number of EB-filled capillaries associated with a noticeable dilatation of the larger vascular channels. Our studies suggest a close interrelationship between post-ischemic microcirculatory hypoperfusion and the development of brain edema, the degree and extent of which progresses with the repetition of ischemic episodes when they are carried out during the periods of hypoperfusion.

Animals↗
PubMed1988

Effect of aminophylline on postischemic edema and brain damage in cats.

We attempted to ameliorate postischemic edema and brain tissue injury in cats by administering aminophylline to reduce the reactive hyperemia that supposedly aggravates both these sequelae. Forty-one cats were subjected to 1 hour of middle cerebral artery occlusion and were killed after 3 hours, 3 days, or 14 days of recirculation; one half of the cats received 0.916 ml/kg of a 25 mg/ml solution of aminophylline by infusion at a constant rate via the femoral vein starting 10 minutes before release of the occlusion and continuing for 5 minutes after initiation of recirculation; the other half received saline. Regional cerebral blood flow was monitored by the hydrogen clearance method and water content was evaluated by specific gravity measurements after 3 hours of recirculation; the status of the blood-brain barrier was assessed with Evans blue tracer. Morphologic observations were carried out in cats killed after 3 or 14 days of recirculation. Aminophylline-treated cats killed after 3 hours of recirculation showed significantly reduced hyperemia and edema and no leakage of Evans blue, which was present in all untreated cats killed after 3 hours or 3 days of recirculation. Morphologic observations revealed conspicuously more severe ischemic brain tissue damage in the untreated than in the aminophylline-treated cats after 3 and 14 days of recirculation. Our studies indicate the beneficial effect of administration of aminophylline in the amelioration of postischemic edema and brain tissue injury, which is presumably achieved by reduction of reactive hyperemia.

Aminophylline↗
PubMed1987

Pathophysiological aspects of brain edema.

Two mayor types of brain edema, related to two different pathomechanisms, can be recognized: 1) cytotoxic type-where the main feature is the swelling of cellular elements of brain parenchyma and 2) vasogenic type-where an increased vascular permeability leading to accumulation of edema fluid in the extracellular spaces plays the principal role. In this type of edema, there is a close interrelationship between extravasation of serum proteins and retention of water in the brain tissue. In the ischemic brain edema both cytotoxic and vasogenic mechanisms are involved. A biphasic opening of the blood-brain barrier, associated with vasogenic edema, is observed following release of major cerebral artery occlusion. The first opening of the barrier is related to a reactive hyperemia which follows promptly recirculation. The second opening, recognizable after a delay, is associated with a severe ischemic brain tissue injury.

Blood Flow Velocity↗
PubMed1987

Experimental model for repetitive ischemic attacks in the gerbil: the cumulative effect of repeated ischemic insults.

An experimental model for repeated ischemic attacks, which allows easy induction of cerebral ischemia of any desired duration and frequency, has been developed in the gerbil. With this procedure, a pronounced cumulative effect on development of edema and tissue injury was observed using 3 separate, 5-min bilateral occlusions of the common carotid arteries spaced at various time intervals. This effect was most evident when the occlusions were carried out at 1-h intervals, i.e., during the period of marked postischemic hypoperfusion. Such animals, killed after 24 h of recirculation, showed significantly more severe edema and brain tissue injury in the areas exposed to ischemia than was observed in animals killed 24 h after single 5- or 15-min occlusions. The changes of regional CBF, assayed with a [3H]nicotine method, indicated a relatively rapid onset of hypoperfusion of similar degree after each release of arterial occlusion. The hypoperfusion recovered significantly within 6 h of recirculation following either single or multiple occlusions, and no residual hypoperfusion was observed in animals which, when killed at 24 h, showed severe edema and brain tissue injury. This model should prove useful in elucidating the pathophysiological mechanisms operative in repetitive cerebral ischemia.

Animals↗
PubMed1987

Blood-brain barrier and ischaemic brain oedema.

According to classification of brain oedema into the cytotoxic and vasogenic types, the latter is closely related to the changes in permeability of the BBB. In cerebral ischaemia, although both types of oedema are involved, the important role of vasogenic oedema, associated with BBB changes, is increasingly recognized. This particularly applies to temporary arterial occlusions in which a biphasic character of two independent BBB openings has been described. The first opening, related mainly to haemodynamic factors, allows leakage of serum proteins into brain tissue and induces vasogenic oedema. The intensity of this oedema can be diminished by reducing the reactive hyperaemia, which promptly follows the release of arterial occlusion. According to recent investigations, infusion of aminophylline appears to be promising in this respect. The other circulatory disturbance, which can affect development of post-ischaemic oedema, is related to the post-ischaemic hypoperfusion which follows reactive hyperaemia. The repeated ischaemic insults during the period of hypoperfusion lead to a pronounced cumulative effect intensifying greatly ischaemic brain oedema and tissue injury.

Blood Proteins↗
PubMed1986

Pathophysiological aspects of blood-brain barrier permeability in epileptic seizures.

Blood-brain barrier (BBB) permeability to macromolecules was assessed during seizures induced by pentylenetetrazole, bicuculline, methoxypyridoxine, methionine sulfoximine, and kainic acid. It was observed that each convulsant induced a specific pattern of regional BBB opening. This was, however, only the case when systemic blood pressure (BP) rose with seizure onset. The analysis of regional cerebral blood flow revealed that a high increase in flow in rabbits with BP rise is related to the normal flow at rest in the single brain region, but not to BBB permeability. In rabbits without BP increase, regional flow increase was low but well modulated and is possibly a better indicator for neuronal activity. The ultrastructural analysis showed that macromolecular transport over the cerebrovascular endothelium is by pinocytosis, an neurotransmitter controlled process. It is suggested that seizure-induced regional BBB opening is determined by two factors: release of neurotransmitters due to the process of auto-regulation during peripheral pressure increase, and change in local neurotransmitter milieu due to the action of the convulsant and/or the seizure activity.

Animals↗
PubMed1986

The blood-brain barrier to horseradish peroxidase at the onset of bicuculline-induced seizures in hypothalamus, pallidum, hippocampus, and other selected regions of the rabbit.

Rabbits were subjected to bicuculline-induced generalized seizures of 15-min duration to elucidate the mechanism by which the macromolecule horseradish peroxidase (HRP) traverses the blood-brain barrier (BBB) in specific brain areas. Transendothelial pinocytosis at the level of arterioles was the main route of passage. In addition, in thalamus and hippocampus pinocytotic vesicles were observed in capillaries. In thalamus, hypothalamus and septum vesicles in the endothelium of venules were also present. Repeatedly, pinocytotic vesicles were ejecting their content into the interendothelial clefts, so that the presence of HRP reaction product between adjacent tight junctions cannot be considered a conclusive evidence for their opening. The HRP, which had reached the neuropil due to the seizure-evoked BBB opening, accumulated in the interstitial spaces and penetrated the synaptic cleft. Uptake of the tracer in vesicular form into presynaptic boutons, presumably excitatory ones as diagnosed by their ultrastructural features, was observed in all brain regions. The uptake was rare in septum, periaqueductal gray, hypothalamus, and cerebellar cortex; frequent in pallidum, hippocampus, and medulla oblongata; and very intense in thalamus. Uptake in postsynaptic dendrites was present mostly in the vicinity of boutons. Incorporation into glial processes was rare and confined to perivascular astrocytes. It is suggested, that HRP traverses the BBB by regionally selective, transmitter-controlled pinocytotic transport and that the neuronal uptake of the foreign protein is at least partially dependent on the involvement of synapses of particular brain regions in the paroxysmal activity during the generalized seizures.

Animals↗
PubMed1986

Influence of blood-brain barrier opening to proteins on development of post-ischaemic brain injury.

The effect of the BBB opening to proteins on development of post-ischaemic brain injury was assessed in 32 cats subjected to one hour MCA occlusion. The CBF was measured by hydrogen clearance from electrodes inserted in the caudate and the cerebral cortex within the MCA territory. In 16 animals, a prevention of subsequent reactive hyperaemia was attempted by hypovolaemia, produced by withdrawal of blood just before the release of MCA occlusion. The hypovolaemia was successful in prevention of post-ischaemic hyperaemia in five out of eight cats sacrificed at 3 h and in six out of eight animals killed after 3 and 14 days. In cats sacrificed 3 h after release of MCA occlusion, ischaemic sites, associated with reactive hyperaemia, showed evidence of BBB breakdown to proteins and significantly more severe oedema than at the ischaemic sites without reactive hyperaemia, which otherwise failed to reveal leakage of EB tracer. In the cats sacrificed at 3 and 14 days, the ischaemic sites which showed reactive hyperaemia after release of MCA occlusion, revealed much more severe ischaemic brain tissue injury than was observed at the sites without reactive hyperaemia, which also did not show any EB leakage. The present study indicates that reactive hyperaemia, which follows release of major cerebral artery occlusion, may play a significant role in the breakdown of the BBB to proteins, and in increasing the severity of post-ischaemic oedema and of ischaemic brain tissue injury.

Animals↗
PubMed1985

The biphasic opening of the blood-brain barrier to proteins following temporary middle cerebral artery occlusion.

The behavior of the blood-brain barrier (BBB) was studied in cats following release after 1-h middle cerebral artery (MCA) occlusion. The regional cerebral blood flow (rCBF) was determined by hydrogen clearance method in the caudate nucleus and the cerebral cortex. The BBB was assayed with Evans blue (EB) tracer and by immunohistochemical peroxidase-antiperoxidase (PAP) method. Following release of MCA occlusion, there were two openings of the BBB, separated by a refractory period. The first opening, occurred shortly after recirculation; this was associated with rCBF below 15 ml/100 g/min during the ischemic period and a pronounced reactive hyperemia promptly following release of MCA occlusion. A refractory period of the BBB was indicated by the absence of EB leakage in cats injected with the tracer 30 min before killing at 3 h after recirculation, although the rCBF values in these animals were even lower (6 +/- 1 ml/100 g/min) during occlusion, and all of them showed a pronounced hyperemia after recirculation. The occurrence of the previous BBB opening in these animals was confirmed by the PAP staining. The second opening of the BBB was observed at 5 and 72 h after recirculation in cats which were injected with EB 30 min before killing, and which showed rCBF below 15 ml/100 g/min during occlusion, followed by a pronounced reactive hyperemia. No EB extravasations were observed at any time in cats in which the rCBF during occlusion was above 15 ml/100 g/min and which failed to show a marked reactive hyperemia.

Animals↗
PubMed1985

Ultrastructural observations on the transvascular route of protein removal in vasogenic brain edema.

Micro-blood vessels (MBVs), located in the area of edema, were studied in cat brain at various time intervals (1 h, 24 h, 7 days) after cold-lesion injury. Both cold-injured and adjacent gyri were examined for blood-brain barrier (BBB) permeability to i. v. injected horseradish peroxidase (HRP) with circulation times of 40 min and 24 h. Evans blue (EB) was used as a tracer for gross evaluation of the extension of brain edema. Localization of alkaline phosphatase (AP) and binding of cationized ferritin (CF), considered as a marker of anionic sites, were also studied ultrastructurally. Twenty-four hours after cold injury, the extravasated edema fluid, outlined by EB tracer, was observed to be spreading through the white matter (WM) into the adjacent gyrus. At this time, numerous, larger than capillary MBVs, presumably arterioles and venules located in the edematous WM, showed accumulations of HRP injected at the time of the operation, in the basement membrane, in abluminal pits, and in numerous pinocytotic vesicles and vacuoles of endothelial cells (ECs). The animals killed after 24 h with 40 min HRP circulation showed extravasation of HRP tracer in a zone underlying the necrotic cold injury lesion. On the other hand, there was no evidence of an abnormal HRP leakage in the further removed areas of edema in the WM, particularly in the adjacent gyrus.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1985

Role of extracellular proteins in the dynamics of vasogenic brain edema.

The relationship between extravasation of proteins into extracellular spaces of brain parenchyma and the water content of such regions were evaluated in an experimental model. In this model, a temporary opening of the blood-brain barrier (BBB) to proteins was produced without significant injury to the cellular elements of brain tissue. Rabbits were subjected to bolus injection of their own blood under 360-400 mm Hg pressure via the internal carotid artery. The opening of the barrier and its duration were evaluated with Evans blue (EB), horseradish peroxidase (HRP), and sodium fluorescein (NaFl) tracers. The water content of brain tissue was assessed by specific gravity (SG) measurements in 1-mm-diameter tissue samples. Quantitative evaluation of protein penetration into brain tissue was carried out using 125I bovine serum albumin (BSA). The opening of the BBB to proteins persisted up to 9 h, whereas the barrier remained permeable to small molecular NaFl for 24 h. The SG measurements indicated in the areas of EB extravasation a progressive increment in water content up to 9 h, i.e., the duration of BBB opening to proteins. Following this, there was a progressive clearance of edema in spite of the BBB remaining open for NaFl for 24 h. Quantitative evaluations of 125I-BSA and SG in the same tissue samples, supported by statistical analysis, indicated approximately linear relationship analysis, indicated approximately linear relationship between albumin and water, implying a strong correlation between the development of vasogenic edema and extravasation of proteins into extracellular spaces.

Animals↗
PubMed1985

Incongruence of regional cerebral blood flow increase and blood-brain barrier opening in rabbits at the onset of seizures induced by bicuculline, methoxypyridoxine, and kainic acid.

Cerebral blood flow (CBF) was estimated using [3H]nicotine as tracer in 18 discrete rabbit brain regions at the onset of generalized seizures induced by bicuculline (BC), methoxypyridoxine (MP), and kainic acid (KA) and compared with the previously described regional pattern of blood-brain barrier (BBB) opening. Regional CBF increased 3- to 5-fold in BC-seizures, 2- to 3-fold (except in inferior colliculus) in MP-seizures, and twofold (no change in inferior colliculus) and periaqueductal gray) in KA-seizures. In general, CBF elevation was greater in areas with a high original CBF, and below average in regions with a low control value. However, under each condition a few areas did not follow this rule, viz. the occipital cortex and the basal part of the cerebellar vermis with low flow values in BC-seizures, the inferior colliculus with no change and the pallidum with a relatively high flow during MP-seizures, and limbic system areas with an exceptionally high flow during KA-seizures. The usual rise in arterial blood pressure (BP) at the onset of the seizure, necessary for the development of a BBB lesion, was absent in a few animals with BC- and MP-seizures, yet, their CBF was elevated in most regions although to a lesser extent. No relationship appeared to exist between the rise in CBF and the regional pattern of BBB opening. It is concluded that a loss of cerebral autoregulation is a prerequisite for BBB leakage, but the location of the opening is determined by neuronally derived factors which differ from convulsant to convulsant and from brain region to brain region.

Animals↗