Cryogenic Lesion Research Articles

Na+-K+-ATPase activity of glial, neuronal, and synaptosomal enriched fractions from normal and freezing-injured rabbit cerebral cortex.

This paper investigates the kinetic parameters of Na+-K+-ATPase in glial, neuronal, and synaptosomal enriched fractions isolated from rabbit cerebral cortex. Under normal conditions, kinetic parameters-Vmax and KK+0.5- of Na+-K+-ATPase are the same in the three fractions, suggesting that this enzyme behaves as the same molecular entity. Following a cryogenic lesion, the alterations of these parameters appear to be different in the different fractions. These data suggest that the same enzyme exhibits various responses when exposed to the same pathological event. The dissimilar lipid composition of the Na+-K+-ATPase environment, and/or different adaptative responses to abnormal ion concentrations in glial, neuronal, and synaptosomal fractions could account for these different responses.

The early phase of cryogenic lesions: an experimental model of seizures updated.

Following cryogenic lesions in 64 rabbits, epileptic activity and gray matter edema were correlatively investigated during the initial phase (23 h). Indexes were developed to allow a quantitative assessment of epileptic activity. The indexes demonstrated that the early phase of cryogenic epilepsy is a very rapid phenomenon during the first 4 h postlesion. Epileptic activity precedes brain edema, and in individual animals, there is a significant positive correlation between the total amount of epileptic activity and the total amount of edema. The relationship between epileptic activity and brain edema are most likely interrelated at the level of pathophysiological mechanisms and several mechanisms can be postulated.

Experimental carbon dioxide laser brain lesions and intracranial dynamics: Part 3. Effect on cerebral blood flow.

Experimental carbon dioxide brain lesions were created over the intact dura mater of the left parietooccipital region of the anesthetized albino rabbit (40-watt impacts of 0.5-second duration, for a total of 4 seconds, with 0.5-second intervals between impacts), and cerebral blood flow (CBF) studies were performed with the hydrogen clearance technique. The animals were mechanically ventilated to maintain a constant PaCO2. Blood pressure, central venous pressure, electroencephalogram, and intracranial pressure were continuously monitored. The control CBF before lesion was 64.1 +/- 15.8 and 70.9 +/- 13.4 ml/100 g/minute for the left and the right hemispheres, respectively. CBF studies at 2, 4, 6, 8, and 24 hours after the lesion did not significantly change from the control values, save for a trend to increase over the right hemisphere only at 2 hours (range 106.0 +/- 55.4 to 41.6 +/- 9.3). It is concluded that in this model the changes in intracranial pressure and brain edema that are seen and have been previously reported are not due to change in cerebral circulation. The brain edema that results probably has characteristics similar to those seen in the cryogenic lesion (vasogenic) model, and this could account for the rise in intracranial pressure.

Cat area 17. II. Response properties of infragranular layer neurons in the absence of supragranular layer activity.

Response properties of cells in the infragranular layers of cortical area 17 of the cat were examined in the absence of input from supragranular layers. Supragranular activity was silenced either reversibly by cooling the surface of cortex or permanently by making a cryogenic lesion of the supragranular layers. Visually driven responses of cells throughout the cortical column were recorded with a linear array of electrodes. Most infragranular layer cells continued to be visually responsive in the absence of supragranular layer input. These cells were similar to normal infragranular layer cells on measures of visual responsiveness, orientation selectivity, and direction selectivity. Special complex, but not standard complex, cells were absent in layer 5 when supragranular layers were destroyed. We found no evidence for a selective effect of removal of supragranular activity on the response properties of cells in layer 6. We propose that the intracolumnar projection from the supragranular layers drives the special complex cells of layer 5, but is not necessary for the visual driving of most other infragranular layer cells. This projection does not impose selectivity for stimulus orientation or direction on the remaining active cells of the infragranular layers.

An experimental study on the effects of DMSO and indomethacin on cerebral circulation and intracranial pressure

Albino rabbits with a cryogenic lesion to the left parieto-occipital cortex had cerebral blood flow studies (CBF) with the hydrogen clearance technique 24 hours after the insult. Similar subgroups were treated with DMSO (1 g/kg) bolus, DMSO (2 g/kg) infusion, indomethacin (20 mg/kg) bolus, and indomethacin followed by DMSO. Following DMSO bolus administration there was an immediate rise in CBF over both hemispheres, with a significant paradoxical decrease at 30 minutes, followed by a second smaller rise at 60 minutes. With DMSO infusion, the rise in CBF was sustained throughout the infusion period with no paradoxical decrease. With indomethacin there was an initial decrease immediately following the drug, and at 60 minutes there was a rise in the insulted left hemisphere, more than the right one. Indomethacin administration 15 minutes prior to DMSO failed to halt the immediate increase in CBF noted following DMSO bolus injection. These results, together with the changes that occurred in intracranial pressure and brain water content, are analyzed.

Brain water and aging.

Brain water content and Na/K-ATPase activity have been compared in two groups of rats aged 60 +/- 5 days (group I) and 630 +/- 10 days (group II). In group II control animals, brain water content (p less than 0.001) and Na/K-ATPase activity (p less than 0.02) were found to be significantly reduced. Following a cryogenic lesion of the brain, the increase in water content was larger in group I (not significant), whereas impairment of Na/K-ATPase activity was much more pronounced in group II (p less than 0.001).

Inflammation-induced stimulation of the synthesis of prostaglandins and lipoxygenase-reaction products in rabbit cornea.

The cyclooxygenase and lipoxygenase pathways that produce prostaglandins (PGs) and hydroxyeicosatetraenoic acids (HETEs) were studied in inflamed rabbit cornea. A cryogenic lesion was induced and five days later the epithelium, stroma and endothelium were isolated and incubated with [1-14C]arachidonic acid. After lesioning, the arachidonic acid metabolites, thromboxane B2, PGF2 alpha and 6-keto-PGF1 alpha exhibited the greatest increase in the stroma. Lipoxygenase products were formed in the three layers also, although 12-HETE predominated. The correlation between the synthesis of these compounds and corneal injury is discussed.

125I-antibody autoradiography and peptide fragments of albumin in cerebral edema.

The regional distribution of albumin in serum extravasations of cerebral edema was visualized on intact brain slices by autoradiography of 125I-labeled antibodies directed against albumin. Following autoradiographic imaging of edema protein spread, concentrations of total serum proteins were determined by radioimmunoassay in tissue micro samples taken from various regions of the brain. Peptide fragments of albumin--produced upon proteolytic breakdown of the native protein in vivo--were separated by affinity chromatography and HPLC. The combination of techniques for imaging, direct quantification, and analysis of molecular structure of serum proteins was provided to be valid in three different types of experimental cerebral edema in the rat: cortical cryogenic lesion, brain tumors, and stroke-prone spontaneous hypertension. The results indicate differences in the reactivity of edematous tissue with respect to proteolytic activity, depending on the susceptibility of serum proteins to in vivo fragmentation.

Intracranial hypertension and brain oedema in albino rabbits. Part 3: Effect of acute simultaneous diuretic and barbiturate therapy.

Increased intracranial pressure due to brain oedema was produced in albino rabbits by combining a cryogenic lesion in the left hemisphere with the intraperitoneal administration of 6-aminonicotinamide (cytotoxic agent). The following parameters were assessed: intracranial pressure (ICP), systolic arterial pressure (SAP), central venous pressure (CVP), EEG, brain water and electrolyte content, gross pathology, and blood brain barrier integrity. Acute therapy to reduce ICP was performed by administering a bolus of mannitol (1 gm/kg) and 30 minutes later, also in bolus, frusemide (5 mg/kg). Immediately following the administration of mannitol an infusion of pentobarbitone was commenced; this was continued for one hour so that a total of 10 mg/kg was administered. There was a 50% reduction of ICP at one hour from initiation of treatment. The brains of the animals were extracted immediately upon cessation of therapy (pentobarbitone) and they revealed a significant reduction of water content for the right, uninjured, hemisphere only, when compared to controls; a slight but not significant reduction of the brain sodium and potassium was noted in both hemispheres. There was no change noted in the gross pathology and extent of blood brain barrier breakdown. In all animals epinephrine infusion had to be administered for between 20 and 30 minutes to maintain a SAP over 80 torr. There seems to be no advantage in the simultaneous administration of barbiturates and diuretics for the control of ICP due to brain oedema.

Acute dimethyl sulfoxide therapy in experimental brain edema: Part I. Effects on intracranial pressure, blood pressure, central venous pressure, and brain water and electrolyte content.

Albino rabbits with experimental brain edema produced by a cryogenic lesion or by a cryogenic lesion combined with a metabolic blocker, 6-aminonicotinamide, were given 1 g of a 10% solution of dimethyl sulfoxide (DMSO) per kg by intravenous bolus. Simultaneous recording of intracranial pressure (ICP), systemic arterial pressure (SAP), and central venous pressure and electroencephalography were performed while the animals were mechanically ventilated at a constant PaCO2 (PaCO2, 38 to 42 torr). One hour after the administration of DMSO, the rabbits were killed by air embolus, and the brain was removed promptly for the determination of wet and dry weights and electrolyte content. The ICP at 15, 30, and 60 minutes after DMSO was lower in both groups; ICP was significantly lower at 30 minutes (p less than 0.5) in the cold lesion group and at 15 minutes in the combined group (p less than 0.05). These was no significant change in SAP after DMSO in either group. There was s significant reduction of brain water content after DMSO in the combined lesion group (p less than 0.005 for the left hemisphere and p less than 0.025 for the right); there was no significant reduction of water content in the group with a cold lesion only.

Glial fibrillary acidic protein in cryogenic lesions of the rat brain

Histologic sections of rat brains obtained at time intervals ranging from 30 min to 48 h following a cryogenic lesion placed on the surface of the parietal lobe, were immunocytochemically stained for glial fibrillary acidic (GFA) protein (glial filaments), IgG and albumin. Intense staining for the GFA protein and enlargement of astrocytes in the subcortical white matter and corpus callosum, were demonstrated near the lesion at 30 min and spread throughout the white matter up to 48 h. The early reaction of the astrocytes suggests that disassembly of glial filaments or new GFA synthesis may contribute to astrocytic changes.

Massive doses of steroids in cryogenic cerebral injury and edema.

Cryogenic lesions were produced in the brains of rhesus monkeys and the accompanying edema measured by quantitative chemical methods. No effect on this type of edema could be demonstrated in animals treated with massive doses of steroids.

Cerebral blood flow in the monkey after focal cryogenic injury.

A focal cryogenic lesion was made in the left superior frontal gyrus of the anesthetized macaque brain. Cerebral blood flow (CBF) was determined by the hydrogen clearance technique before and during the 4 hours following trauma. Local CBF in tissue adjacent to the lesion increased in the first half hour after the lesion was made and then decreased during the ensuing 3 1/2 hours. Local CBF in the contralateral superior frontal gyrus, as well as total CBF and oxygen consumption, were unchanged by cryogenic trauma. The spread of vasogenic edema into uninjured tissue probably accounts for the observed decrease in local CBF. This experimental model may assist in discovering therapy to alter favorably the spatial and temporal profile of pathologic CBF changes in tissue surrounding an acute lesion of the brain.

Effects of Intracarctid Injections of Reserpine on Cerebral Tissue

Therapeutic effectiveness of the catecholamine depleting agent, reserpine, has been reported in one type of cerebrovascular injury, the cryogenic lesion, to result in reduced edematous involvement (1). Other assessments of the effects of reserpine on cerebral oxidative phosphorylation and arterial blood pressure have been carried out. To our knowledge, however, no previous ultra structural studies have been done following reserpine treatment either in normal cerebral tissue or in ischemic tissue . The importance of determining the effect of reserpine on normal cerebral tissue ultra structure is emphasized by the reported observations of ultra structural changes in rat pituitary (2), mouse abdominal sympathetic paraganglia (3), and the subclavian glomera of the rabbit (4) following reserpine injection.

Experimental study of relation of fever to cerebral edema

✓ The effect of hyperthermia on the development of the cerebral edema associated with cryogenic lesions was studied in monkeys. Exposure to a body temperature of near 104°F for a period of only 2 hours increased the edema by 40%. This effect was independent of the hypertensive action of hyperthermia but was intensified when the latter was present. It is suggested that, in human diseases known or thought to be associated with cerebral edema, fever should be vigorously treated.

Cryogenic lesions in the ventrolateral nucleus and pulvinar. Fusimotor effects.

Lesions of the ventrolateral nucleus (VLN) of the thalamus relieve limb hypertonia in humans through mechanisms that are essentially unknown. To test the hypothesis that a decrease of muscle spindle activity may be involved, experiments were performed to determine the effects of lesions in VLN on the responses to muscle extension of medial gastrocnemius spindle primary afferents in the cat. The effect of pulvinar lesions was also studied. The lesions were produced by a stereotaxically placed cryogenic probe. Ventrolateral nucleus lesions significantly depressed spindle afferent responses with probe tip temperatures of —20 C, but lesions of the pulvinar did not depress spindle afferent responses despite cooling to —60 C. It is concluded that the VLN has a net excitatory effect on hindlimb extensor fusimotor neurons. This finding is compatible with the view that a depression of fusimotor activity after VLN lesions is an important mechanism underlying the beneficial effects of such lesions in humans with limb hypertonia.

A surgical investigation of the clinical physiology of the LP-pulvinar complex in man

Cryogenic stereotactic lesions were placed in 55 pulvinar and 9 lateralis-posterior (LP) nuclei of 49 patients suffering from dystonia, athetosis, spasticity, torticollis, intractable pain, and other miscellaneous conditions. Ten of 19 cases (52.5%) of dystonia, 10 of 16 cases (62.5%) of athetosis and 7 of 10 cases (70%) of spasticity improved significantly following the cryogenic lesion. Thirteen patients with primary or secondary intractable pain were pain-free following surgery. No deleterious effects on motor, sensory, behavioral, or speech and language functions were noted. Electrophysiological studies during surgery not only helped in localisation of the pulvinar and LP nuclei but a wide distribution of evoked potentials from cortex was recorded following their stimulation. It appears that the pulvinar of man contributes to motor function. The LP-pulvinar complex is a poly-sensory data processor, contributing to a wide range of somato-sensory functions.

Technetium in cryogenic cerebral injury and edema.

The distribution of technetium given as the pertechnetate ion and as the diethylenetriaminepentacetic acid chelate was studied in the brains of dogs with cryogenic lesions. There was more of the chelate than the free form in the necrotic lesion. The radioactivity of the tissue, four hours after injection of the isotope, was compared to the values at 15 minutes. The greatest increase in radioactivity was found in the edema fluid but the concentration of the isotope in both forms was significantly less than that in the serum. The experimental model was then compared to human disease. It was concluded that a scan at four hours should be superior to a 15-minute scan and that a careful comparison of early and late scans could give a quantitative measure of the edema surrounding brain tumors.

Cryogenics in Surgery.

This volume competently fulfills its objectives: ... to provide the clinician with a summary of the current status of cryosurgery—from the basic biology to the clinical applications: and finally to the new and promising areas still to be explored. The introduction and the 17 chapters of this book were written by acknowledged leaders in the field of cryosurgery. Their work during the past two decades has made possible the controlled use of freezing for many problems whose treatment was previously impossible or hazardous. In addition to information about the role of cryotherapy in ophthalmology, otology, neurosurgery, plastic surgery, urology, orthopedics, gynecology, and dermatology, the reader will find helpful facts about cryobiology, cryoinstrumentation, cryoimmunology, and experimental cryosurgery. For the mathematically proficient, there is an impressive section on mathematical predictions of the cryogenic lesion. Photographs, tables, and diagrams are profuse and clear; references are pertinent. My only criticism is the failure of the

Experimental and clinical evaluation of a British cryogenic lesion maker.

Experimental and clinical evaluation of a British cryogenic lesion maker.