Biomedical subjects

M Marsala

Publications and source records attributed to M Marsala.

At least 55 records · Page 3Linked to original sources

PubMed1996

Changes in spontaneous unit activity in lumbar spinal cord after reversible aortic occlusion in the rat.

Lumbar dorsal horn neuronal multiunit activity was recorded in the halothane anesthetized rat before, during, and after a 30 min interval of spinal cord ischemia induced by inflation of a balloon catheter inserted through the femoral artery. After initiation of ischemia, there was typically a brief burst of neuronal activity, followed by electrical silence. During reperfusion, there was a progressive increase in discharge activity over the ensuing 30 min. Spontaneous activity was significantly increased, as measured by the number of discriminable cells and frequency of discharges. Post-ischemic hyperactivity reached maximal values typically after 60-90 min of reperfusion. The character and time course of recorded activity are consistent with the behavioral sequelae of transient spinal ischemia.

Animals↗

PubMed1996

Characterization of time course of spinal amino acids, citrulline and PGE2 release after carrageenan/kaolin-induced knee joint inflammation: a chronic microdialysis study.

Pharmacological studies have implicated the spinal activation of excitatory amino acids, nitric oxide, and prostaglandins systems in the development of tactile and thermal hypersensitivity and central sensitization after peripheral inflammation. In the present study, using a chronically placed loop dialysis catheter, we examined in the unanesthetized rat the effect of carrageenan/kaolin (C/K)-induced knee joint inflammation on the time course of spinal release of several active factors including excitatory amino acids (glutamate, aspartate), citrulline (a marker of nitric oxide formation), and prostaglandin E2 (PGE2) as well as the concomitant development of tactile and thermal hypersensitivity. Infection of C/K in the knee evoked a significant release of glutamate, with an initial peak seen immediately after knee C/K injection (179 +/- 22%) and with a progressive and consistent increase over a period of 24 h (153-186%). Comparable changes in the concentration of aspartate (123-179%) were observed. Citrulline was constantly above baseline for the 24-h period (121-158%). PGE2 was significantly increased at 10 min (146 +/- 11%) with no change observed between 3-5 h. At 24 h, PGE2 was again significantly (143 +/- 18%) increased. Behaviorally, a prominent thermal and tactile allodynia developed after injection with the peak seen by 1-3 h after induction of the inflammation. This hypersensitivity state, while diminished in its intensity, persisted for the entire observation period. These data suggest that increased spinal release of excitatory amino acids (EAA), nitric oxide and/or PGE2 is involved in the maintenance of the pain state initiated by acute peripheral inflammation.

Amino Acids↗

PubMed1996

Effect of spinal kainic acid receptor activation on spinal amino acid and prostaglandin E2 release in rat.

Current work has shown that spinal excitatory amino acid receptor activation can evoke physiological phenomena that may be mediated by the subsequent depolarization of glutamate-containing neurons and the activation of cyclo-oxygenase systems. To investigate this phenomenon, rats were implanted with lumbar intrathecal loop dialysis catheters for perfusion and an additional lumbar intrathecal PE-10 catheter for drug delivery. Two days after implantation, kainic acid (1 microgram) was injected intrathecally under light (0.5%) halothane anaesthesia and the spinal release of several amino acids and prostaglandin E2 was examined. Resting concentrations (mean expressed as pmol/25 microliters) of glutamate (89), aspartate (9), serine (387), glycine (597), taurine (185), asparagine (113) and prostaglandin E2 (0.43) were observed. Intrathecal kainic acid produced significant signs of arousal in the rat and evoked a significant increase (mean +/- S.E.M. of % baseline concentration) in aspartate (445 +/- 127%) and glutamate (221 +/- 35%). Prostaglandin E2 concentration was increased in the second post-injection sample (180 +/- 36%). Intrathecal pretreatment with 6-cyano-7-nitroquinoxaline-2, 3-dione (3 micrograms or 10 micrograms), a non-N-methyl-D-aspartate receptor antagonist, blocked amino acid but not prostaglandin E2 release after kainic acid injection. Pretreatment with MK-801 (10 micrograms; non-competitive NMDA receptor antagonist) had no significant effect on evoked release of amino acids or prostaglandin E2. Indomethacin (10 micrograms, a cyclo-oxygenase inhibitor) pretreatment significantly decreased baseline prostaglandin E2 release in control animals (61 +/- 6%) and suppressed kainic acid-evoked aspartate, taurine and prostaglandin E2 release, but had no effect on the concentration of glutamate after kainic acid injection. These data suggest that activation of spinal kainic acid receptors provides a powerful stimulus for secondary excitatory amino acid release and, consistent with the concurrent appearance of prostaglandin E2, that this release is potentiated by the release of a cyclo-oxygenase product.

Animals↗

PubMed1996

Effect of proximal arterial perfusion pressure on function, spinal cord blood flow, and histopathologic changes after increasing intervals of aortic occlusion in the rat.

BACKGROUND AND PURPOSE: Cross-clamping of the thoracic aorta results in spinal cord ischemia and prominent systemic hypertension. Using a rat model of transient spinal cord ischemia. we examined the effects of manipulation of proximal aortic blood pressure on spinal cord blood flow (SCBF), neurological dysfunction, and changes in spinal histopathology after increasing intervals of aortic occlusion. METHODS: Aortic occlusion was induced by the inflation of a 2F Fogarty catheter placed into the thoracic aorta in rats anesthetized with halothane (1.5%). A tail artery was cannulated to monitor distal arterial pressure (DAP). To measure SCBF, a laser probe was implanted into the epidural space of the L-2 vertebra. To manipulate proximal arterial pressure (PAP), the left carotid artery was cannulated with a 20-gauge polytetrafluoroethylene catheter to permit blood withdrawal and infusion from a peripheral reservoir during aortic occlusion. In a survey study, spinal cord ischemia was induced in single animals at intervals of 6, 10, 15, 30, or 40 minutes with PAP controlled at 40, 60, 80, and 110 to 120 mm Hg. In a second series, ischemia was induced in groups of animals for 0, 6, 8, 10, and 12 minutes with PAP controlled at 40 mm Hg. After ischemia the animals survived for 2 to 3 days. During this recovery period, neurological functions were evaluated, followed by quantitative histopathology of the spinal cord. RESULTS: Under normal conditions, cross-clamping yields an acute proximal hypertension (125 to 135 mm Hg), a fall of DAP to 15 to 22 mm Hg, and a decrease in SCBF to 7% to 11% of baseline values. With the use of the external reservoir, proximal hypertension could be abolished and the PAP maintained at target pressures. In these studies a typical syndrome of tactile allodynia, spastic paraplegia, and necrotic changes affecting the central part of the gray matter after 24 to 48 hours of reperfusion was observed at the following combinations of ischemic intervals and PAP values: > 10 minutes/40 mm Hg; > 12 minutes/60 mm Hg; > 16 minutes/80 mm Hg; and > 30 minutes/uncontrolled. Lowering PAP resulted in a corresponding decrease in residual SCBF. Systematic studies at a PAP of 40 mm Hg at occlusion intervals of 6, 8, 10, and 12 minutes revealed that 100% of rats were paraplegic after 10- and 12-minute ischemia, and these rats showed corresponding signs of spinal histopathology. CONCLUSIONS: The present study shows that systemic intraischemic hypotension (40 mm Hg) significantly potentiates neurological dysfunction after transient aortic occlusion. The mechanism of the observed effect may include elimination of collateral flow during aortic occlusion and/or consequent potentiation of hypoperfusion during reperfusion. These data indicate that PAP during occlusion should be monitored and/or controlled because it is a critical variable in the determination of outcome in this model of spinal cord ischemia.

Animals↗

PubMed1996

Intrathecal nicotinic agonist-elicited release of excitatory amino acids as measured by in vivo spinal microdialysis in rats.

The nicotinic agonists, nicotine and cytisine, when administered intrathecally elicit an increase in blood pressure and heart rate as well as a nociceptive response. By using a novel microdialysis procedure, in which a 4-cm dialysis tubing is inserted proximal to the intrathecal injection site, we have examined the release of excitatory amino acids associated with agonist stimulation. The nicotinic agonists, nicotine, cytisine and epibatidine, elicit dose-dependent increases in spinal release of Asp and Glu. The rank order of potencies of the nicotinic agonists in eliciting the cardiovascular and irritation responses correlates with the order of agonist potency in inducing Asp and Glu release in spinal microdialysates. In addition, a correlation is observed between the nociceptive and blood pressure response evoked by the nicotinic agonists and the spinal release of the excitatory amino acids. By examining the position of the permeable dialysis surface in relation to the agonist injection port, we found that the response to nicotine is localized to 5 to 10 mm distances, whereas the cytisine response may be elicited over longer distances. The marked desensitization observed upon repeated administration of cytisine is also reflected in diminished amino acid release. Amino acid release by nicotine can be antagonized by a channel blocking antagonist, mecamylamine, and by a competitive antagonist, dihydro-beta-erythroidine. Mecamylamine also inhibited the amino acid release elicited by epibatidine and cytisine. Hence, excitatory amino acid release is an appropriate response marker for the cellular events associated with nicotinic receptor stimulation in the spinal cord.

Animals↗

PubMed1996

[Excitatory amino acids and prostanoids release in spinal cord injury].

UNLABELLED: Acute spinal cord trauma may initiate a cascade of hemodynamic and biochemical events characterized by direct mechanical destruction of neurons, hemorrhages and significant increases in active substances (glutamate, prostaglandins (PGs), ets.). However, there are no data which define the effect of acute spinal cord trauma on biochemical changes in the spinal cord. The aim of the present study was to examine time-dependent biochemical changes in the spinal cord by intrathecal microdialysis in the acute stage of spinal cord turama. METHODS: Male Sprague-Dawley rats (300-325g) were implanted with a dialysis catheter and PE-10 catheter in the intrathecal space of the lumbar spinal cord. Three days later the animals were anesthetized with halothane and 10-min dialysis samples were collected. Compression spinal cord injury was produced by inflating an extradural 2F-Fogarty balloon catheter (L4-L5) for 60 sec. After compression, samples were collected while the animals remained anesthetized for 30 min, and additional samples were collected until 4hr post-injury. At the end of the dialysis period neurological function was briefly evaluated. Microdialysate samples were analyzed for glutamate, aspartate, and taurine by HPLC-UV and for PGE2 by RIA. RESULTS: Compression of the spinal cord caused significant increases in the levels of all amino acids. The greatest in creases were in glutamate and aspartate at 10 min, followed by a decrease over the rest of the 4-hr period. Similarly, PGE2 showed an immediate increase after compression, with normalization between 1-2 hr, but this was followed by a secondary increase at 2-4 hr. Neurologically, all animals displayed complete paralysis with loss of sensory function that remained unchanged for the 4-hr period. COMMENT: The present study clearly demonstrated the time course of spinal amino acids and PGE2 release by using a chronically implanted dialysis catheter after spinal cord compression and also showed a correlation with neurological deterioration. These biochemical changes in the extracellular space may display various, multiphasic patterns reflecting progressively developing edema and corresponding ischemia.

Animals↗

PubMed1995

The spinal loop dialysis catheter: characterization of use in the unanesthetized rat.

To permit long-term measurement of time-dependent changes in levels of dialyzable drugs and transmitters in the spinal intrathecal (i.t.) space of the unanesthetized rat, we developed a dialysis catheter for chronic placement. This was accomplished by constructing a loop probe 9 cm in length from 0.3-mm-diameter dialysis tubing that was made impermeable except for the distal loop. This loop catheter was readily inserted though an incision in the cisternal membrane and passed to the lumbar enlargement. The ends of the catheter were then externalized on the top of the head. To permit i.t. injections, an additional i.t. catheter could also be inserted simultaneously by the same route. For dialysis, an external end of the loop catheter was connected to a syringe pump and perfused with artificial CSF (10 microliters/min) and the out flow collected. A series of studies were performed to demonstrate the characteristics and utility of this technique. (1) Stability of resting release: glutamate and glucose concentrations in spinal dialysate showed no significant changes from 3 to 10 days after implantation. (2) Spinal cord ischemia: ischemia induced by aortic occlusion or cardiac arrest evoked a time dependent increase in retrieved glutamate. (3) Spinal cord compression caused a time-dependent glutamate, aspartate and PGE2 increase. (4) Noxious afferent stimulation induced by the injection of formalin into the hindpaw resulted in a rapid and transient increase in dialysate glutamate concentration. (5) Direct activation of spinal excitatory amino acids receptors by i.t. injection of kainic acid (1 microgram) evoked a significant increase in aspartate and taurine. (6) Continuous delivery of spinal opiate (alfentanil) via dialysis resulted in a maintained, concentration dependent elevation in the thermal escape latencies in the unanesthetized rat. The loop dialysis catheter provides a robust experimental tool for studying time dependent changes in the concentration of diffusible substances in spinal CSF over an extended post-implantation interval and allows comparison of these changes with concurrently assessed behavioral indices.

Alfentanil↗

PubMed1995

Effect of prolonged hyperventilation on ischemic injury of neurons after global brain ischemia in the dog.

The influence of prolonged postischemic hyperventilation was studied in the model of global brain ischemia produced by 15 min cardiac arrest in dogs with 8 h recirculation. Histopathological examination of neuronal damage using silver impregnation showed the presence of numerous heavy argyrophylic neurons in the striatum and CA2 hippocampal subfield after 8 h of normoxic reperfusion. In dogs with prolonged 8 h postischemic hyperventilation a reduction in the occurrence of argyrophylic neurons in the striatum and their significant decrease in the hippocampal area were found. Electron microscopic study was performed to characterize the effect of respiratory alkalosis on the ultrastructural changes in neurons and correlate them with the results of silver impregnation. Ultrastructural analysis after the cardiac arrest without recirculation did not reveal the presence of dark neurons within the striatal and hippocampal areas. Neuronal alterations included a decrease in endoplasmic reticulum, mitochondrial swelling and a mild chromatin clumping. After 8 h of normoxic reperfusion many dark, shrinked neurons containing perinuclear clusters of clear vesicles were found. In hyperventilated animals the occurrence of dark neurons with extensive perineuronal edema was substantially reduced in the CA2 subfield. The effect of hyperventilation on postischemic calcium overload is discussed.

Animals↗

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

Intrathecal administration of dizocilpine maleate (MK-801) attenuates ischemic damage in the rabbit spinal cord.

The therapeutic efficacy of intrathecally administered MK-801 (dizocilpine maleate), a noncompetitive receptor antagonist of N-methyl-D-aspartate receptor complex, was investigated in a rabbit spinal cord ischemia model. Normal saline, 0.3 ml (control, n = 4) or MK-801, 150 micrograms in 0.3 ml of saline, was administered intrathecally at the level of the lumbar enlargement, 30 min before (pretreatment, n = 7) or in the first min after (post-treatment, n = 4) 30 min of aortic occlusion followed by 2-h reperfusion. Nauta silver method was used for histopathological evaluation of lumbosacral segments. The degree of gray matter damage (argyrophilic neurons) was evaluated in three areas: A1, Rexed's laminae I-VI; A2, laminae VII and X; and A3, laminae VIII-IX. Pre- and post-treatment with MK-801 decreased the number of argyrophilic neurons (P < 0.05) in all areas examined. The number of argyrophilic neurons in A1, A2, and A3 was reduced by 59, 28, and 29%, respectively, by MK-801 pretreatment and by 87, 66, and 46%, respectively, by MK-801 post-treatment. Our results show that with single bolus intrathecal administration the efficacy of MK-801 was greater with post- compared to pretreatment and most dramatic in Rexed's laminae I-VI compared to laminae VII-X. Intrathecal administration of MK-801 prior to or at the beginning of the recirculation diminishes the extent of postischemic neuronal spinal cord damage at early postreperfusion period.

Animals↗

PubMed1994

Transient spinal ischemia in the rat: characterization of behavioral and histopathological consequences as a function of the duration of aortic occlusion.

To characterize the behavioral and histopathological changes that occur in spinal cord after transient ischemia, reversible occlusion of the descending aorta was achieved in the halothane (1-1.5%)-anesthetized rat by the insertion and subsequent inflation of a 2F Fogarty catheter for 10, 15, 20, or 30 min. Neurological recovery was tested during 8 h of reperfusion. After reflow, animals undergoing 30 min of ischemia displayed an initial flaccidity at 1 h, spasticity at 4 h, and flaccidity at the end of 8 h. Following 20 min of ischemia the initial flaccidity was followed by hindlimb spasticity that persisted for 8 h. Shorter intervals of ischemia had minimal effects on motor function. After reflow, animals developed a prominent allodynea, the incidence of which was dependent on the duration of ischemia. A clear correlation of histopathological changes with the degree of neurological deficit was noted. In spastic animals, small and medium-sized interneurons localized in laminae III to VII were affected. Animals with flaccidity at 8 h additionally displayed a significant incidence of argyrophilic A motoneurons in the ventral horns. Corresponding to the frequent appearance of allodynea, these animals also showed a significant number of damaged neurons in lamina II.

Animals↗

PubMed1994

Transient spinal ischemia in rat: characterization of spinal cord blood flow, extracellular amino acid release, and concurrent histopathological damage.

Extracellular concentrations of amino acids in halothane-anesthetized rats were measured using a microdialysis fiber inserted transversely through the dorsal spinal cord at the level of the lumbar enlargement in conjunction with HPLC and ultraviolet detection. After a 2-h washout and a 1-h control period, 20 min of reversible spinal cord ischemia was achieved by the inflation of a Fogarty F2 catheter passed through the femoral artery to the descending thoracic aorta. After 2 h of postischemic reperfusion, animals were transcardially perfused with saline followed by 10% formalin or 4% paraformaldehyde. The glutamate concentration in the dialysate was significantly elevated after 10 min of occlusion and returned to near-baseline during the first 30 min of reperfusion. Taurine was elevated significantly 0.5 h postocclusion and continued to increase throughout the 2 h of reperfusion. Glycine concentrations showed a tendency to be slightly above baseline during the reperfusion period. Glutamine concentrations modestly increased following 2 h of reperfusion. No significant changes in aspartate, asparagine, and serine were detected. In control animals no significant changes in any amino acids were detected. To assess the role of complete spinal ischemia on spinal glutamate release, studies were carried out using cardiac arrest. Twenty minutes after induction of cardiac arrest, the glutamate concentration was increased about 350-400%. In a separate group of animals, spinal cord blood flow (SCBF) and its response to decreased CO2 were measured using a laser probe implanted into the epidural space at the level of the L2 vertebral segment. SCBF decreased to 5-6% of the control during aortic occlusion. After reversible ischemia, marked hyperemia was seen for the first 15 min, followed by hypoperfusion at 60 min. Under control-preischemic conditions a decrease in arterial CO2 content caused a decrease in SCBF of about 25%. This autoregulatory response was almost completely absent when assessed 60 min after a 20-min interval of aortic occlusion. Histopathological analysis of spinal cord tissue from these animals demonstrated heavy neuronal argyrophilia affecting small and medium-sized neurons located predominantly in laminae III-V. These changes corresponded to signs of irreversible damage at the ultrastructural level. Occasionally, small areas of focal necrosis, located in the dorsolateral part of the dorsal horn and anterolateral part of the ventral horn, were found. The results are consistent with a role for glutamate in ischemically induced spinal cord damage and suggest that taurine elevation detected during the early reperfusion period may serve as an important indicator of irreversible spinal cord neuronal damage.

Amino Acids↗

PubMed1994

Analgesic and neurotoxic effects of intrathecal corticosteroids in rats.

BACKGROUND: Despite the widespread use of epidurally administered corticosteroids in the treatment of sciatica and the failure of animal studies to demonstrate neurotoxicity from epidermally administered corticosteroids, controversy remains regarding the mechanism of action as well as the safety of this treatment. The goal of this study was to determine whether spinally administered corticosteroids have any analgesic effects, and whether repeated intrathecal administration causes any neuronal damage to the spinal cord. METHODS: Chronic lumbar intrathecal catheters were implanted in rats. Formalin testing was carried out 1 h after the intrathecal administration of 400 micrograms methylprednisolone sodium succinate, 48 h after intrathecal administration of triamcinolone diacetate 250 micrograms, or 24 h after the last of a series of four injections of triamcinolone diacetate 250 micrograms given at 5-day intervals. Histologic sections of multiple levels of spinal cord from the animals receiving repeat intrathecal steroid injections were compared to those from animals that received intrathecal saline at the same intervals. RESULTS: The animals receiving repeated intrathecal triamcinolone diacetate demonstrated mild, statistically significant reduction of pain behavior (hindlimb flinching) during the second but not the first phase of the formalin test when compared to controls. No analgesic effects were demonstrated after methylprednisolone sodium succinate or a single injection of triamicinolone diacetate. Animals that received methylprednisolone sodium succinate demonstrated transient segmental allodynia. No behavioral or neurologic abnormalities were seen in any other group. Some histologic evidence neuronal damage (the presence of argyrophilic neurons was seen in the chronically implanted animals in areas of the cord adjacent to the spinal catheters, but there was no difference in incidence of these changes between the steroid and control groups. CONCLUSIONS: Intrathecal steroid injections have no analgesic effect and do not suppress spinal sensitization when administered acutely. After chronic administration, there is a mild effect on nociceptor-driven spinal sensitization (phase 2 of the formalin test), but no analgesic effect on an acute noxious stimulus (phase 1 of the formalin test). Repeated intrathecal administration of triamcinolone diacetate (0.8 mg/kg) is not associated with spinal neurotoxic effects during the time period studied.

Adrenal Cortex Hormones↗

PubMed1994

Effect of graded hypothermia (27 degrees to 34 degrees C) on behavioral function, histopathology, and spinal blood flow after spinal ischemia in rat.

BACKGROUND AND PURPOSE: We used a rat model of reversible spinal ischemia to assess the effect of spinal cord temperature on the development of neurological and histopathologic changes after 20 minutes of reversible aortic occlusion. Spinal cord blood flow and CO2 reactivity was tested by using laser Doppler before and 60 minutes after ischemia. METHODS: In halothane (1%)-anesthetized rats, the spinal cord temperature as assessed by using thermocouple in the paraspinal muscles was lowered to 34 degrees, 31 degrees, or 27 degrees C. After ischemia, spinal cord temperature was raised to 37 degrees C for the next 30 minutes. Animals were maintained in this normothermic condition for 8 hours, after which motor and sensory function were assessed. All animals were then anesthetized and perfused with 10% formalin for light microscopic analysis of spinal cords. RESULTS: In normothermic animals, 20 minutes of ischemia resulted in a loss of CO2 reactivity and hind limb paraplegia with an attendant allodynia that persisted for the 8 hours of reperfusion. Even mild (34 degrees C) hypothermia resulted in significant improvement of neurological function compared with the normothermic group. In paraplegic animals, lumbosacral interneuronal pools localized primarily in laminae III through VII displayed heavy argyrophilic neurons and areas of localized necrosis. In moderate and deep hypothermic animals preservation of CO2 responsivity and complete recovery of neurological function were seen with no detectable histopathologic changes. CONCLUSIONS: These results show that a slight decrease in spinal cord temperature in the peri-ischemic period provides significant protection as measured by histopathology and neurological function.

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↗