Epidural Balloon Compression Research Articles

Selective Calpain Inhibition Improves Functional and Histopathological Outcomes in a Canine Spinal Cord Injury Model.

Calpain activation has been implicated in various pathologies, including neurodegeneration. Thus, calpain inhibition could effectively prevent spinal cord injury (SCI) associated with neurodegeneration. In the current study, a dog SCI model was used to evaluate the therapeutic potential of a selective calpain inhibitor (PD150606) in combination with methylprednisolone sodium succinate (MPSS) as an anti-inflammatory drug. SCI was experimentally induced in sixteen mongrel dogs through an epidural balloon compression technique. The dogs were allocated randomly into four groups: control, MPSS, PD150606, and MPSS+PD150606. Clinical evaluation, serum biochemical, somatosensory evoked potentials, histopathological, and immunoblotting analyses were performed to assess treated dogs during the study. The current findings revealed that the combined administration of MPSS+PD150606 demonstrated considerably lower neuronal loss and microglial cell infiltration than the other groups, with a significant improvement in the locomotor score. The increased levels of inflammatory markers (GFAP and CD11) and calcium-binding proteins (Iba1 and S100) were significantly reduced in the combination group and to a lesser extent in MPSS or PD150606 treatment alone. Interestingly, the combined treatment effectively inhibited the calpain-induced cleavage of p35, limited cdk5 activation, and inhibited tau phosphorylation. These results suggest that early MPSS+PD150606 therapy after acute SCI may prevent subsequent neurodegeneration via calpain inhibition.

Controlled decompression alleviates early brain injury in rabbit intracranial hypertension model by regulating apoptosis/necroptosis.

ABSTRACTPurposeTo evaluate the effects of controlled decompression and rapid decompression, explore the potential mechanism, provide the theoretical basis for the clinical application, and explore the new cell death method in intracranial hypertension.MethodsAcute intracranial hypertension was triggered in rabbits by epidural balloon compression. New Zealand white rabbits were randomly put into the sham group, the controlled decompression group, and the rapid decompression group. Brain water content, etc., was used to evaluate early brain injury. Western blotting and double immunofluorescence staining were used to detect necroptosis and apoptosis.ResultsBrain edema, neurological dysfunction, and brain injury appeared after traumatic brain injury (TBI). Compared with rapid decompression, brain water content was significantly decreased, neurological scores were improved by controlled decompression treatment. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and Nissl staining showed neuron death decreased in the controlled decompression group. Compared with rapid decompression, it was also found that apoptosis-related protein caspase-3/ tumor necrosis factor (TNF)-a was reduced markedly in the brain cortex and serum, and the expression levels of necroptosis-related protein, receptor-interacting protein 1 (RIP1)/receptor-interacting protein 1 (RIP3) reduced significantly in the controlled decompression group.ConclusionsControlled decompression can effectively reduce neuronal damage and cerebral edema after craniocerebral injury and, thus, protect the brain tissue by alleviating necroptosis and apoptosis.

Changes in excursion and strain in the rat sciatic nerve under cauda equina compression induced by epidural balloon inflation

Background contextHealthy nerves are able to stretch and glide as responses to normal physiological movement. Injury to the nerve may alter the nerve's mechanical properties and result in neuropathy. Whether cauda equina compression alters the mechanical properties of the sciatic nerve is still unclear. PurposeThe purpose of this study was to demonstrate the changes in excursions and strains of the sciatic nerve in vivo after acute cauda equina compression was induced by epidural balloon compression. Study designAn animal comparative study with induced cauda equina compression was designed for in situ measurements of nerve properties. MethodsTwenty-six adult Sprague-Dawley rats were divided into three groups. The balloon group (n=10) underwent epidural compression induced by inflation of an embolectomy balloon catheter that was inserted through an L6 laminotomy. The control group (n=10) underwent laminotomy but without compression. The normal group (n=6) received no back surgery. This model of neuropathy was confirmed with electrophysiological examination. The excursions and strains of the sciatic nerve in response to the modified straight leg–raising (SLR) test were measured in situ and analyzed. ResultsThe scales of the excursions were lower in the balloon group than in the other two groups, in both 90° flexion and extension of the knee. The balloon group was more sensitive to positional changes. The strain was significantly higher under the condition of epidural balloon compression. ConclusionsWe concluded that cauda equina compression decreased the excursion and increased the strain of the sciatic nerve in response to a modified SLR test. These findings might indicate one of the mechanisms of the pain provoked by the SLR test and also possibly contribute to an understanding of the pathogenesis of the neuropathy in the lower limbs of patients with cauda equina compression.

Establishment of refractory high intracrinal pressure model in dogs

Objective We expect to have a profound understanding of refractory high intracranial pressure after traumatic brain injury by making a reproducible animal model in dogs experimentally.Method Ten adult dogs were used to make acute epidural balloon compression and decompression models.Changes in mean arterial blood pressure,intracranial pressure and electroencephalography activity were evaluated during the whole compression and three hours after decompression course.Results ( 1 )The mean arterial blood pressure (97.5 ± 7.8 ) mmHg and brain temperature ( 35.6 ± 0.36 ) ℃ had significant increase( P =0.023) and decrease( P ＜ 0.05) respectively in the moment of maximum balloon volume comparing their baseline level ( 83.7 ± 13.0 ) mmHg,( 36.8 ± 0.30 ) ℃.( 2 ) With increase of the balloon volume,ICP rose gradually with cerebral perfusion pressure inversely changed.( 3 ) During decompression,a secondary refractory high intracranial pressure similar to that of balloon compression period occurred (62.2 ± 6.6 ) mmHg.Conclusions Our experiment basically produced a dog model of refractory high intracranial pressure after traumatic brain injury which is similar to the human head injury.It has good reliability and reproducibility.Monitoring of various physiological parameters can provide reasonable evidences for a deeper understanding of its pathogenesis. Key words: Brain injuries; Intracranial hypertension; Models,animal

Early functional outcomes and histological analysis after spinal cord compression injury in rats

Neuroprotective and repair strategies in spinal cord injuries (SCIs) have been so far largely unsuccessful. One of the prerequisites is the use of appropriate preclinical models to decipher pathophysiological mechanisms; another is the identification of optimal time windows for therapeutic interventions. The authors undertook this study to characterize early motor, sensory, autonomic, and histological outcomes after balloon compression of the spinal cord at the T8-9 level in adult rats. A total of 91 rats were used in this study. Spinal cord balloon compression was performed at T8-9 in adult rats by inflation of a 2 Fr Fogarty catheter into the epidural space. The authors first characterized early motor, sensory, and autonomic outcomes of 2 volumes of compression (10 and 15 microl) using behavioral tests and then examined histological outcomes in the spinal cord using Luxol fast blue staining. To further substantiate the characterization of the epidural balloon-compression model, they used a noncompetitive N-methyl-D-aspartate antagonist, GK11, and demonstrated the involvement of excitotoxicity in this model. Proportional and reproducible functional impairment resulted from compression caused by balloon inflation with either 10 or 15 microl of water and corresponded to the extent of the lesion. Indeed, during the early phase following SCI (1 week postinjury), recovery of locomotor function and bladder control correlated with the volume of inflation, whereas outcomes with respect to sensory function and reflexes were independent of compression severity. Treatment with GK11 significantly improved motor function in all groups of rats 1 week after injury and bladder voiding in the 10-microl injured rats compared to the 15-microl injured rats. The results of this study demonstrate that spinal balloon-compression injury in the rat is a well-characterized, reproducible, and predictable model to analyze early events following SCI.

Functional recovery and neural differentiation after transplantation of allogenic adipose-derived stem cells in a canine model of acute spinal cord injury

In this study, we evaluated if the implantation of allogenic adipose-derived stem cells (ASCs) improved neurological function in a canine spinal cord injury model. Eleven adult dogs were assigned to three groups according to treatment after spinal cord injury by epidural balloon compression: C group (no ASCs treatment as control), V group (vehicle treatment with PBS), and ASC group (ASCs treatment). ASCs or vehicle were injected directly into the injured site 1 week after spinal cord injury. Pelvic limb function after transplantation was evaluated by Olby score. Magnetic resonance imaging, somatosensory evoked potential (SEP), histopathologic and immunohistichemical examinations were also performed. Olby scores in the ASC group increased from 2 weeks after transplantation and were significantly higher than C and V groups until 8 weeks (p < 0.05). However, there were no significant differences between the C and V groups. Nerve conduction velocity based on SEP was significantly improved in the ASC group compared to C and V groups (p < 0.05). Positive areas for Luxol fast blue staining were located at the injured site in the ASC group. Also, GFAP, Tuj-1 and NF160 were observed immunohistochemically in cells derived from implanted ASCs. These results suggested that improvement in neurological function by the transplantation of ASCs in dogs with spinal cord injury may be partially due to the neural differentiation of implanted stem cells.

Rapid but not slow spinal cord compression elicits neurogenic pulmonary edema in the rat

The development of neurogenic pulmonary edema (NPE) can be elicited by an immediate epidural balloon compression of the thoracic spinal cord. To evaluate whether a slower balloon inflation could prevent NPE development, we examined the extent of NPE in animals lesioned with a rapid (5 microl - 5 microl - 5 microl) or slow rate (3 microl - 2 microl - 2 microl - 2 microl - 2 microl - 2 microl - 2 microl) of balloon inflation. These groups were compared with the NPE model (immediate inflation to 15 microl) and with healthy controls. Slow balloon inflation prevented NPE development, whereas the pulmonary index and histology revealed a massive pulmonary edema in the group with a rapid rate of balloon inflation. Pulmonary edema was preceded by a considerable decrease in heart rate during the inflation procedure. Moreover, rapid inflation of balloon in spinal channel to either 5 microl or 10 microl did not cause NPE. Thus, a slow rate of balloon inflation in the thoracic epidural space prevents the development of neurogenic pulmonary edema, most likely due to the better adaptation of the organism to acute circulatory changes (rapid elevation of systemic blood pressure accompanied by profound heart rate reduction) during the longer balloon inflation period. It should be noted that spinal cord transection at the same level did not cause neurogenic pulmonary edema.

Low Concentration of Isoflurane Promotes the Development of Neurogenic Pulmonary Edema in Spinal Cord Injured Rats

Anesthetics can either promote or inhibit the development of neurogenic pulmonary edema (NPE) after central nervous system (CNS) injury. The influence of isoflurane was examined in male Wistar rats using 1.5%, 2%, 2.5%, 3%, 4%, or 5% isoflurane in air. Epidural balloon compression of the thoracic spinal cord was performed. The development of NPE was examined in vivo and on histologic sections of lung tissue. Animals anesthetized with 1.5% or 3% isoflurane were behaviorally monitored using the BBB and plantar tests for 7 weeks post-injury. The spinal cord was examined using MRI and morphometry of the spared white and gray matter. All animals from the 1.5% and 2% groups developed NPE. Almost 42% of the animals in the 1.5% group died of severe pulmonary hemorrhage and suffocation; x-rays, the pulmonary index, and the histological picture revealed a massive NPE. More than 71% of the animals from the 2.5% and 3% groups did not develop any signs of NPE. Blood pressure after spinal cord compression rose more in the 1.5% group than in the 3% one. In the 1.5% group, the sympathetic ganglionic blockade prevented the neurogenic pulmonary edema development. Animals from the 3% group recovered behaviorally more rapidly than did the animals from the 1.5% group; morphometry and MRI of the lesions showed no differences. Thus, low levels of isoflurane anesthesia promote NPE in rats with a compressed spinal cord and significantly complicates their recovery. The optimal concentration of anesthesia for performing a spinal cord compression lesion is 2.5-3% isoflurane in air.

Establishment of a canine spinal cord injury model induced by epidural balloon compression

A model that provides reproducible, submaximal yet sufficient spinal cord injury is needed to allow experiments leading to development of therapeutic techniques and prediction of clinical outcome to be conducted. This study describes an experimental model for spinal cord injury that uses three different volumes of balloon inflation and durations of compression to create a controlled gradation outcome in adult dogs. Twenty-seven mongrel dogs were used for this study. A 3-french embolectomy catheter was inserted into the epidural space through a left hemilaminectomy hole at the L4 vertebral arch. Balloons were then inflated with 50, 100, or 150 µl of a contrast agent at the L1 level for 6, 12, or 24 h and spinal canal occlusion (SCO) measured using computed tomography. Olby score was used to evaluate the extent of spinal cord injury and a histopathologic examination was conducted 1 week after surgery. The SCO of the 50, 100, and 150 µl inflations was 22-46%, 51-70%, and 75-89%, respectively (p < 0.05). Olby scores were diminished significantly by a combination of the level of SCO and duration of inflation in all groups. Olby scores in the groups of 150 µl-12 h, 150 µl-24 h, and 100 µl-24 h were 0.5, 0, and 1.7, respectively. Based on these results, a SCO > 50% for 24 h, and > 75% for 12 h induces paraplegia up to a week after spinal cord injury.

Establishment of a canine spinal cord injury model induced by epidural balloon compression

Establishment of a canine spinal cord injury model induced by epidural balloon compression

Dispersion of cerebral temperature, cerebral perfusion and intracranial pressure in rabbits placed with epidural balloons

This study examines the intracranial pressure and temperature dispersion in a rabbit model after epidural balloon compression. Right and left supratentorial, intraventricular and infratentorial pressures and temperatures of the rabbits have been measured before epidural balloon was placed. Afterwards, the epidural balloon was placed in right parietal epidural area. The intracranial pressure and temperature dispersion values were recorded after inflation with 0.3 and 0.6 ml, respectively. The control values of intracranial pressure measurements of four different brain regions were found to be similar. When the balloon was inflated to 0.3 ml, the intracranial pressure distribution was found to be equal in all the fields. After the balloon was inflated up to 0.6 ml, right and left supratentorial intracranial pressure values were found to be equal. However, infratentorial pressure values were lower and intraventricular pressure values were higher when compared with the right hemisphere. Before the inflation and at two different inflation volumes, perfusion pressure and temperature dispersion were found to be similar between right hemisphere and other compartments. We conclude that, the effective mechanism in cerebral temperature regulation may be related to preserved cerebral perfusion pressure and cerebral blood flow.

Intracranial volume reserve determination using CT images, numerical analysis and lumbar infusion tests. An experimental study.

The epidural balloon compression model in the cat was used in intracranial volume reserve studies. The evaluation of the intracranial volume-pressure relations was based on the lumbar infusion test data: intracranial pressure, CSF outflow resistance, volume-pressure response and on CT images numerical analysis (CTINA) values. Two methods were applied and compared in the study: lumbar infusion test and CT images numerical analysis. The determinations were performed at the balloon volumes of 0.5 ml, 1.0 ml, and 1.5 ml. First statistically significant changes were found at the balloon volume of 0.5 ml i.e. the increase of CSF outflow resistance and volume-pressure response (data obtained in lumbar infusion test) and the decrease in CTINA values. The rise of intracranial pressure was less informative as it was observed at the balloon volume of 1.5 ml. Therefore CTINA seems to be a very useful noninvasive screening method in clinical studies of intracranial volume reserve.

Rebound of ICP after brain compression

The rebound of intracranial pressure (ICP) occurring after decompression of an intracranial mass lesion was studied in an epidural balloon compression model. Intracranial morphology and brain tissue water content were assessed with magnetic resonance imaging (MRI). Fast and slow components of the transverse relaxation time (T2) were used as indicators of brain oedema development. During balloon compression a progressive prolongation of both the fast and the slow T2 components took place. Following deflation of the balloon both components increased rapidly, particularly the slow-T2. The MR scans displayed progressive occlusion of the aqueduct, and obliteration of the ambient and pontine cisterns. The changes in morphology and in water content after decompression had largely the same time course as the development of the rebound of ICP. In contrast, no changes in morphology and tissue water content occurred after hydrostatic brain compression achieved by subarachnoid fluid infusion. The findings suggest that the intracranial pressure rebound is caused by cerebral oedema accumulated during and particularly in the recirculation phase after an ischaemic injury of adequate intensity and adequate duration.

An epidural intracranial pressure monitor for experimental use in the rat.

We described the construction and use of a simple and reliable catheter system that can be used to monitor intracranial pressure (ICP) from the epidural space in rats in an experimental setting. The catheter system is easily fabricated in the laboratory from readily available materials. The monitor is fitted flush with the inner table through a burr hole in the temporal squama. A side port is used to fill the system with saline and to irrigate the system should be catheter become obstructed. The distal end of the catheter is fitted to a pressure transducer that is connected to a graphic display and recording system. This system was used to record ICP in 30 anaesthetized adult rats. Seven were subjected to baseline ICP recording only and 23 were subjected to baseline recordings followed by epidural balloon compression of the contralateral hemisphere. Baseline ICP varied between 0 and 8 mmHg and respiratory variation could be detected on the tracings for 24 rats (75%). ICP responded directly and sensitively to epidural balloon inflation in all 23 rats tested. In 5 rats that died during balloon inflation, the decrease in ICP after death followed closely the loss of arterial blood pressure. There was a close correlation of numerical values obtained in two rats in which ICP was recorded simultaneously from the epidural catheter and from a catheter in the subarachnoid space at the cisterna magna. In one rat in which ICP increased to more than 70 mmHg, the epidural catheter continued to record ICP accurately while the cisternal catheter became obstructed with herniated brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravascular aggregation after acute intracranial hypertension by epidural balloon compression in cats.

The authors have studied the effect of acute intracranial hypertension produced by placement of an epidural balloon (control group) in cats, on cerebral perfusion, evoked responses, and hematological parameters. These elements were measured in similarly injured animals which underwent isovolemic hemodilution with dextran 75, after relief of intracranial hypertension. Four hours after balloon deflation, perfusion was markedly impaired in 30% of the control group, and was reduced to 11% in the dextran-infused group. The suppressed N1 amplitude of somatosensory evoked responses on the compression side, the reduced platelet aggregability, and the erythrocyte-deformability by intracranial hypertension were all significantly more restored in the dextran-infused group after decompression. The percentage of platelets with volumes between 21.75 and 48.75 cu mu (normal 9.75 to 12.75 cu mu) significantly increased after decompression. Activation of platelets during intracranial hypertension leads to an increase in platelet volume from platelet aggregation, and correlates with a decrease in platelet aggregability. It was also suggested that reduction of erythrocyte deformability was not caused by erythrocyte aggregation. The authors emphasize the role of intravascular factors such as vascular obstruction by platelet aggregates, and difficulty in passage of erythrocytes through capillaries due to reduced deformability, in the disturbance of the microcirculation following acute intracranial hypertension. The protective effect of dextran 75 by inhibition of platelets as well as hemodilution is stressed.

Effects of a cerebral vasodilator agent (Praxilene) on cerebral hemodynamics in acute intracranial hypertension and cerebral edema

Twenty mongrel dogs were used and the effects of the vasodilator "Praxilene" (2 mg/Kg i.v.) on cerebral blood flood flow (CBF), oxygen availability (O2a) and intracranial pressure (ICP) were srudied in acute intracranial hypertension produced by slow inflation of epidural balloon and in cerebral edema produced by epidural application of dry ice for ten minutes. The local CBF was measured by the heat clearance method with double thermister or thermocouple, while measuring O2a by polarograph using open tip type of platinum electrode with the diameter of 50 to 270μ. ICP was measured by epidural microballoon method. In normal controls, CBF was increased for 9.6 minutes after the administration of Praxilene (2 mg/Kg i.v.) approximately as much' as that after 10% CO2 inhalation of 4 or 5 minutes, and the elevation of O2a was paralleled to the increase of CBF. But ICP was elevated by mean 7.2 mmHg by the administration of Praxilene, while 10% CO2 inhalation elevated ICP by mean 18.7 mmHg. Therefore, Praxilene increased CBF with less increase of ICP than 10% CO2 inhalation. In acute intracranial hypertension by epidural balloon compression, CBF and O2a were not increased so much by the administration of Praxilene as controls with normal ICP. When ICP was raised to the level higher than 30 to 50 mmHg, Praxilene induced further increase of ICP and the harmful effects on systemic circulation such as hypotension, arrhythmia and bradycardia. Under these condition CBF and O2a were no longer increased. Cerebral edema was produced in five experiments. CSF pressure was measured by cisternal puncture at 24 to 48 hours after injury. It was ranged from 8 to 11 mmHg in all cases. CBF and O2a were measured in the lesion and in the contralateral normal area. O2a electrode was located at the same point where CBF electrode was inserted. In two of five experiments, CBF and O2a were not increased within the lesion by the administration of Praxilene In other three experiments, CBF was increased slightly by it, but the effects of Praxilene to CBF and O2a were abolished when ICP was elevated to the level of 25 to 30 mmHg by hydrostatic infusion of artificial CSF into the cisterna magna. However, in these condition CBF and O2a were increased by it in the contralateral normal area. These effects would be probably due to the decrease of the vasoreactivity to the vasodilator "Praxilene" and the abnormal hemodynamics within the lesion due to the regionally increased ICP. In some cases, it was noticed that O2a was not increased in spite of increase of CBF within the lesion by the administration of Praxilene or 10% CO2 inhalation. This would demonstrate that there were some regions within the lesion where the increased CBF was non-nutritional. In conclusion, the effect of vasodilator "Praxilene" would not be expected in the patients with intracranial hypertension more than 30 to 50 mmHg, and in those with cerebral edema even if ICP is not elevated.

Experimental studies on the effect of trauma, infarction and other cerebral lesion upon conduction of the nerve impulse in the central nervous system.

Summary1. The antidromic pyramidal response of the cat has been studied under normal control conditions and following cerebral insults simulating various clinical pathological states.2. Two types of response have been noted. The first type which is associated with early epidural cerebral compression or compression resulting from the intracerebral injection of blood is characterized by an obvious decrease in conduction velocity and less marked immediate changes in amplitude.The second type of response has been found in acute asphyxia, in cerebral infarction produced by occlusion of the middle cerebral artery, and in cerebral edema resulting from 24 hours of epidural balloon compression. It is characterized by a marked decline in amplitude of potential and a less obvious delay in conduction time.3. The electrical response of the pyramidal tract has been found to be highly susceptible to anoxia. This is in striking contrast to the relative resistance to oxygen want seen in peripheral nerves. Cerebral infarction with its more abrupt local deprivation of oxygen and with the sudden reduction in availability of metabolic substrate produces an even more rapid disappearance in electrical response than that seen in general asphyxia.4. Routine electron microscopic studies and special efforts to determine the ultra‐structural localization of sodium in the axon of the internal capsule have been carried out in brains subjected to various cerebral insults. In mild cerebral compression the axoplasm has shown little alteration and there is to be seen only occasional sodium precipitation inside the axonal membrane. In cerebral infarction the axon showed much more severe changes and may even lose its continuity. Sodium precipitation is widespread. In cerebral edema, in addition to moderate structural alteratons, abundant precipitates of sodium pyroantimonate may be seen inside the axonal membrane.5. It has been postulated that the changes of the first group depend upon a physical alteration in the axon while those in the second group reflect metabolic disturbances and structural changes occurring in the axonal membrane.

Protein and enzyme alterations in experimental brain injury.

Increased intracranial pressure was produced in the cat by epidural balloon compression. An increase in the activity of sodium-potassium-adenosine triphosphatase was detected in compressed brain compared to the control brain. Alterations in the acetylcholinesterase isozymes were detected with polyacrylamide electrophoresis. Evidence obtained by immunological means suggests the release of synaptic membrane antigens following cerebral injury.