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Cervical spinal cord injury usually results in cardiorespiratory dysfunctions due to interruptions of the bulbospinal pathways innervating the cervical phrenic motoneurons and thoracic sympathetic preganglionic neurons. The present study aimed to evaluate the therapeutic effects of adrenergic agents on systemic and spinal hemodynamics during acute cervical spinal cord injury. In vivo animal study. The cardiorespiratory function and spinal cord blood flow and oxygenation level were monitored in response to cervical spinal cord contusion and intravenous infusion of three types of adrenergic agents (phenylephrine, dobutamine, and norepinephrine). Cervical spinal cord contusion resulted in immediate reduction of respiratory airflow, arterial blood pressure, and spinal cord blood flow. The arterial blood pressure and spinal cord blood flow remained lower than the preinjury value in contused animals infused with saline at 60 min postinjury. Infusion of phenylephrine (500, 1000, and 2000 μg/kg) and norepinephrine (125, 250, and 500 μg/kg) significantly increased the arterial blood pressure, while only norepinephrine augmented the spinal cord blood flow. Conversely, dobutamine (1000 and 2000 μg/kg) reduced both arterial blood pressure and spinal cord blood flow. Notably, administration of adrenergic agents tended to increase spinal cord hemorrhage in contused animals. Infusion of norepinephrine can effectively maintain the blood pressure and improve spinal cord blood flow during acute spinal cord injury. Norepinephrine may be a superior medicine for hemodynamic management; however, the potential hemorrhage should be considered when utilizing the vasopressor to regulate systemic and spinal hemodynamics at the acute injured stage. [ABSTRACT FROM AUTHOR]

Central cord syndrome is a form of incomplete spinal cord injury appearing in the anesthesia literature primarily in trauma. Our institution recently managed a rare, life-threatening central cord syndrome following an uneventful anterior cervical discectomy and fusion which uniquely presented as respiratory depression progressing to quadriplegia. This patient's dramatic experience began nearly indistinguishably from more common etiologies of respiratory depression in the post-anesthesia care unit before blossoming swiftly into quadriplegia. We review the details of her presentation and pathophysiology with a message of vigilance to the anesthesia provider. Interpretation of her clinical exam and rapid intervention were key to preventing a lethal outcome. Central cord syndrome should be considered by anesthesiologists in the differential for respiratory depression following cervical spine surgery.

This study investigates the effect of extended laminectomy (EL) on spinal cord injury (SCI) caused by spinal shortening, and further, the timing and the optimal length of removal. Dogs received spinal column shortening at T13 segment, following which the control group underwent regular laminectomy while other groups underwent laminectomy with an additional 1-lamina length removed 6h after shortening ("1-lamina EL 6 h"), an extra 1.5-lamina length resected at 6 h or 12 h after shortening ("1.5-lamina EL 6 h" and "1.5-lamina EL 12 h"), and an extra 2-lamina length removed at 6 or 12 h after shortening ("2-lamina EL 6 h" and 2-lamina EL 12 h"), respectively. Somatosensory evoked potential (SSEP) and neurological function were recorded periodically; spinal cord blood flow (SCBF) and nerve cell apoptosis were detected. The results showed that resection of an additional 1-lamina length appeared inadequate to relieve the sharp kinking of the spinal cord, whereas the kinking disappeared with an additional 2-lamina length resection. The "1-lamina EL 6 h" and "1.5-lamina EL 12 h" groups showed no significant differences from the control in latency of SSEP, SCBF, hindlimb function and apoptosis. By contrast, significant recovery of SSEP, SCBF and hindlimb function as well as reduction of apoptosis were presented in other three groups. The "2-lamina EL 6 h" group, in particular, showed the most prominent recovery. In conclusion, an additional resection of two laminae at 6 h after shortening showed the best effect in alleviating SCI. Timely and adequately extended laminectomy could be a potential therapeutic strategy for SCI attributable to spinal shortening. [ABSTRACT FROM AUTHOR]

Central cord syndrome is a form of incomplete spinal cord injury appearing in the anesthesia literature primarily in trauma. Our institution recently managed a rare, life-threatening central cord syndrome following an uneventful anterior cervical discectomy and fusion which uniquely presented as respiratory depression progressing to quadriplegia. This patient's dramatic experience began nearly indistinguishably from more common etiologies of respiratory depression in the post-anesthesia care unit before blossoming swiftly into quadriplegia. We review the details of her presentation and pathophysiology with a message of vigilance to the anesthesia provider. Interpretation of her clinical exam and rapid intervention were key to preventing a lethal outcome. Central cord syndrome should be considered by anesthesiologists in the differential for respiratory depression following cervical spine surgery. [ABSTRACT FROM AUTHOR]

Purpose: To determine the safe range of shortening the spinal column at middle thoracic spine and to observe the changes in blood-spinal cord barrier (BSCB), microglia/macrophage activation and inducible nitric oxide synthase (iNOS) activity after shortening-induced spinal cord injury.Methods: Dogs were allocated to four groups. Group A (control) underwent laminectomy of T7 without shortening the spinal column. Groups B, C and D had 1/3, 1/2, and 2/3 of T7 resected, respectively, followed by spinal shortening. Somatosensory evoked potential (SSEP) and hind-limb function were recorded periodically for 14 days after operation. Spinal cord blood flow (SCBF) and BSCB were detected at the acute phase of shortening. Microglia/macrophage reactions and iNOS activity were observed by immunohistochemistry.Results: Shortening of 1/3 of a vertebral height caused no significant changes in SSEP and hind-limb function after operation, whereas shortening of 1/2 of the height caused SSEP abnormality and paraparesis, and severe neurologic deficit of hind-limb was observed when the shortening reached 2/3 of the height. SCBF increased temporarily and showed a trend of recovery when the shortening was within 1/2 of a vertebral segment height. When it reached 1/2 or 2/3 of the height, SCBF at 6 h post-operation was 86.33% or 74.95% of the baseline, and an increasing BSCB permeability was observed. In the subsequent 7 days, obvious activation of macrophage and increased number of iNOS-positive cells were observed.Conclusion: It is safe to shorten the spinal cord within 1/3 of a vertebral height in middle thoracic spine under two-segment laminectomy in canine. The BSCB disruption, macrophage activation, and increased iNOS activity were observed in the acute phase of the injury. These slides can be retrieved under Electronic Supplementary Material. [ABSTRACT FROM AUTHOR]

Study Design: Porcine model.Objective: To quantify critical vascular and mechanical events that occur before and during an evolving spinal cord injury.Summary Of Background Data: Spinal cord injuries are one of the most devastating complications in spine surgery. Intraoperative neuromonitoring changes can occur as a secondary event of spinal cord compression and decrease in spinal cord blood flow (SCBF). Laser Doppler flowmetry has been well validated for measuring blood flow.Methods: Seventeen pigs were studied, 14 of which completed the experiment. Multilevel, midthoracic laminectomies were performed. Laser Doppler flowmetry electrodes were placed on the dura to measure SCBF. Spinal cord injury was induced by incremental balloon inflation in the epidural space. The animals were separated into two groups. After motor-evoked potential (MEP) loss, group A underwent medical interventions and then balloon decompression approximately 20 minutes later. Group B underwent immediate balloon decompression followed by medical interventions. After interventions, wake-up test was performed and computed tomography scan measured thoracic spinal canal volume.Results: Median SCBF changes were seen 15.8 (5.4-25.1) minutes before MEP loss. However, the 20% threshold interval was often reached before. At the 20% threshold, median pressure was 7 psi, balloon volume was 0.5 cm, and 50% of the spinal canal was compromised. In group A, no pigs moved and all had pathology indicating ischemia. In group B, 9 of 10 were found to be moving their hind legs with 7 indicating ischemia.Conclusion: Compression spinal cord injury is the end of a cascade involving increasing intracanal pressure, decreasing canal volume, and hypoperfusion. Rapid relief of compression leads to MEP return. SCBF monitoring can detect ischemia preinjury, giving surgeons an opportunity for early intervention.Level Of Evidence: 4. [ABSTRACT FROM AUTHOR]

Background: During thoracoabdominal aortic surgery, the spinal cord is placed under ischemic conditions. Elevation of systemic blood pressure is thus recommended as a method of increasing the blood supply from collateral networks. This study examined the mechanisms by which noradrenaline administration increases spinal cord blood flow (SCBF) by elevating systemic blood pressure., Methods: In beagles ( n = 7), the thoracoabdominal aorta and L2-L7 spinal cord segmental arteries (SAs) were exposed and a distal perfusion bypass was created to simulate clinical practice. SCBF was measured by laser flowmetry at the L5 dura mater and spinal cord perfusion pressure (SCPP) was measured inside the clamped aorta. The six pairs of SAs from L2 to L7 were clamped, and mean systemic blood pressure (mSBP), SCBF, and SCPP were measured before and after clamping and after starting continuous infusion of noradrenaline at 0.5 µg/kg/min. Rates of change in systemic vascular resistance (SVR) and spinal cord vascular resistance (SCVR) were calculated from the measured values., Results: With no SA clamping (control), the rate of increase in SCVR was 0.74 times the rate of increase in SVR (y = 0.2 + 0.74x, r = 0.889, r 2 = 0.789; P < 0.01). When all six pairs of SAs were clamped, a weak correlation was evident between rate of change in SCVR and rate of change in SVR, and the rate of increase in SCVR was lower than the rate of increase in SVR (y = 0.39 + 0.07x, r = 0.209, r 2 = 0.039; P < 0.01). When all six pairs of SAs were clamped in the absence of distal perfusion, a weak correlation was also evident between rate of change in SCVR and rate of change in SVR, and the rate of increase in SCVR was lower than the rate of increase in SVR (y = 0.19 + 0.08x, r = 0.379, r 2 = 0.144; P < 0.01)., Conclusions: The rate of increase in SCVR induced by noradrenaline administration was lower than the rate of increase in SVR in the control group with no spinal cord SA clamping and in both experimental groups with clamped SAs (with and without distal perfusion), creating an environment conducive to spinal cord flow distribution., Competing Interests: None to declare., (Copyright 2023, Kise et al.)

The main purpose of the present study was to examine the time-dependent alterations in the endothelial cell density that occur in the first 180 days after irradiation of the spinal cord and the functional role of these alterations in the spinal cord blood flow. An irradiated cervical spinal cord rat model (C2-T2 segment) was generated using a 60 Co irradiator to deliver 30 Gy. A significant loss of forelimb motor function was observed 180 days post-irradiation. The number of neurons in the anterior horn of the spinal cord began to decrease significantly 3 days post-irradiation compared with normal controls, reaching the lowest number at 90 days post-irradiation. A significant reduction in the endothelial cell density was observed from 14 days post-irradiation in the white matter and from 3 days post-irradiation in the gray matter. The lowest endothelial cell density was reached at 30 days post-irradiation in the white matter and at 60 days post-irradiation in the gray matter. A significant reduction in the microvessel density was observed from 3 days post-irradiation in both the white matter and the gray matter. The lowest microvessel density was reached at 90 days post-irradiation in both the white matter and the gray matter. A significant reduction in the relative magnitude of spinal cord blood flow was observed from 21 days post-irradiation. The lowest relative magnitude of spinal cord blood flow was reached at 90 days post-irradiation. We did not find any evidence of demyelination. The results revealed that a single 30-Gy irradiation dose resulted in impaired forelimb motor function, a decreased number of neurons, and reduced endothelial cell density, microvessel density and relative magnitude of spinal cord blood flow. However, a 30-Gy single-dose irradiation was not sufficient to induce demyelination in the rat spinal cord. [ABSTRACT FROM AUTHOR]

Background At present, no effective clinical treatment is available for the late effects of radiation myelopathy. The aim of the present study was to assess the therapeutic effects of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in a rat model of radiation myelopathy. Methods An irradiated cervical spinal cord rat model was generated. UC-MSCs were injected through the tail vein at 90, 97, 104 and 111 days post-irradiation. Behavioral tests were performed using the forelimb paralysis scoring system, and histological damage was examined using Nissl staining. The microcirculation in the spinal cord was assessed using von Willebrand factor (vWF) immunohistochemical analysis and laser-Doppler flowmetry. The microenvironment in the spinal cord was determined by measuring the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the serum and the anti-inflammatory cytokines brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in the spinal cord. Results Multiple injections of UC-MSCs through the tail veil decreased the forelimb paralysis, decreased spinal cord histological damage, increased the number of neurons in the anterior horn of the spinal cord, increased the endothelial cell density and the microvessel density in the white matter and gray matter of the spinal cord, increased the relative magnitude of spinal cord blood flow, down-regulated pro-inflammatory cytokine expression in the serum, and increased anti-inflammatory cytokine expression in the spinal cord. Conclusion Multiple injections of UC-MSCs via the tail vein in a rat model of radiation myelopathy significantly improved the microcirculation and microenvironment through therapeutic paracrine effects. [ABSTRACT FROM AUTHOR]

Purpose: In the acute phase of spinal cord injury (SCI), ischemia and parenchymal hemorrhage are believed to worsen the primary lesions induced by mechanical trauma. To minimize ischemia, keeping the mean arterial blood pressure above 85 mmHg for at least 1 week is recommended, and norepinephrine is frequently administered to achieve this goal. However, no experimental study has assessed the effect of norepinephrine on spinal cord blood flow (SCBF) and parenchymal hemorrhage size. We have assessed the effect of norepinephrine on SCBF and parenchymal hemorrhage size within the first hour after experimental SCI. Methods: A total of 38 animals were included in four groups according to whether SCI was induced and norepinephrine injected. SCI was induced at level Th10 by dropping a 10-g weight from a height of 10 cm. Each experiment lasted 60 min. Norepinephrine was started 15 min after the trauma. SCBF was measured in the ischemic penumbra zone surrounding the trauma epicenter using contrast-enhanced ultrasonography. Hemorrhage size was measured repeatedly on parasagittal B-mode ultrasonography slices. Results: SCI was associated with significant decreases in SCBF ( P = 0.0002). Norepinephrine infusion did not significantly modify SCBF. Parenchymal hemorrhage size was significantly greater in the animals given norepinephrine ( P = 0.0002). Conclusion: In the rat, after a severe SCI at the Th10 level, injection of norepinephrine 15 min after SCI does not modify SCBF and increases the size of the parenchymal hemorrhage. [ABSTRACT FROM AUTHOR]

Purposes: Cerebrospinal fluid (CSF) pressure elevation may worsen spinal cord ischaemia after spinal cord injury (SCI). We developed a rat model to investigate relationships between CSF pressure and spinal cord blood flow (SCBF). Methods: Male Wistar rats had SCI induced at Th10 ( n = 7) or a sham operation ( n = 10). SCBF was measured using laser-Doppler and CSF pressure via a sacral catheter. Dural integrity was assessed using subdural methylene-blue injection ( n = 5) and myelography ( n = 5). Results: The SCI group had significantly lower SCBF ( p < 0.0001) and higher CSF pressure ( p < 0.0001) values compared to the sham-operated group. Sixty minutes after SCI or sham operation, CSF pressure was 8.6 ± 0.4 mmHg in the SCI group versus 5.5 ± 0.5 mmHg in the sham-operated group. No dural tears were found after SCI. Conclusion: Our rat model allows SCBF and CSF pressure measurements after induced SCI. After SCI, CSF pressure significantly increases. [ABSTRACT FROM AUTHOR]

Coupling of the cardiovascular and cerebrospinal fluid (CSF) system is considered to be important to understand the pathophysiology of cerebrovascular and craniospinal disease and intrathecal drug delivery. A coupled cardiovascular and CSF system model was designed to examine the relation of spinal cord (SC) blood flow (SCBF) and CSF pulsations along the spinal subarachnoid space (SSS). A onedimensional (1-D) cardiovascular tree model was constructed including a simplified SC arterial network. Connection between the cardiovascular and CSF system was accomplished by a transfer function based on in vivo measurements of CSF and cerebral blood flow. A 1-D tube model of the SSS was constructed based on in vivo measurements in the literature. Pressure and flow throughout the cardiovascular and CSF system were determined for different values of craniospinal compliance. SCBF results indicated that the cervical, thoracic, and lumbar SC each had a signature waveform shape. The cerebral blood flow to CSF transfer function reproduced an in vivolike CSF flow waveform. The 1-D tube model of the SSS resulted in a distribution of CSF pressure and flow and a wave speed that were similar to those in vivo. The SCBF to CSF pulse delay was found to vary a great degree along the spine depending on craniospinal compliance and vascular anatomy. The properties and anatomy of the SC arterial network and SSS were found to have an important impact on pressure and flow and perivascular fluid movement to the SC. Overall, the coupled model provides predictions about the flow and pressure environment in the SC and SSS. More detailed measurements are needed to fully validate the model. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) produces acute hemodynamic alterations through disruption of sympathetic output of the autonomic nervous system and places individuals with SCI at high risk of secondary ischemic insult to the spinal cord as well as to other organs. The purpose of this study was to examine hemodynamics and serum vasopressin concentration in the acute period following complete cervical SCI in piglets. We developed a new model of traumatic complete cervical SCI in piglets and measured acute hemodynamic variables and serum arginine vasopressin (AVP) concentrations at baseline and for 4 h after SCI under fentanyl anesthesia. Complete cervical SCI caused an immediate tachycardia which lasted for approximately 1 h, immediate hypotension which was sustained for the 4-h duration of the study, decreases in both systemic and pulmonary vascular resistance, and a compensatory increase in cardiac output, which resulted initially from an increase in heart rate (HR) but was later sustained after resolution of tachycardia by an increase in cardiac stroke volume. Serum AVP concentration increased significantly after SCI and did not change in the control group. Neurogenic shock did not occur due to the robust increase in cardiac output and cardiac stroke volume. Complete cervical SCI produces hemodynamic alterations consistent with the withdrawal of sympathetic tone. Although mean arterial pressure (MAP) decreased significantly after SCI, the increase in serum vasopressin may have played a role in maintaining blood pressure and preventing circulatory collapse, a complication which is encountered frequently in patients with cervical and upper thoracic SCI. [ABSTRACT FROM AUTHOR]

Study design:Experimental laboratory investigations with a model of neurotrauma in Macaca rhesus.Object:The present study evaluates whether intrathecal papaverine induces changes in spinal cord blood flow (SCBF) of injured spinal cord and prevents secondary injury.Setting:Institute of Spinal Cord Injury, Sun Yat-sen University, China.Methods:After laminectomy was performed and contusive spinal cord injuries were induced in adult female Macaca rhesus, three received intrathecal papaverine, and three received saline 0.9% for control. SCBF was registered by laser-Doppler recording technique continuously for 180 min after injection. Histological analyses and microvessel density (MVD) were used for evaluation of spinal cord injury, and the percentage of spared spinal cord area was calculated.Results:Mean arterial blood pressure showed no significant change in both groups. In the papaverine group, SCBF recovered to 81.35±7.8% of baseline at 15 min, 75.24±6.3% at 30 min, 73.38±2.3% at 90 min and 72.57±4.1% at 180 min after the completion of infusion. SCBF was significantly higher than the control groups (P<0.01). There was no occlusion of the arteries, but occluded veins were identified at the injured site. The MVD in the spinal cord of the control group was significantly lesser than the papaverine group (P<0.01). Luxol Fast Blue staining showed that intrathecal papaverine reduced myelin loss in the lesion 2 weeks after injury (P<0.05).Conclusion:Intrathecal administration of papaverine increased SCBF in non-human primates. It is likely that the effects of papaverine can reduce secondary injury in spinal cord injured Macaca rhesus.Spinal Cord (2008) 46, 716–721; doi:10.1038/sc.2008.30; published online 15 April 2008 [ABSTRACT FROM AUTHOR]

The article reports on the safety and efficacy of 2 types of bioresorbable/biocompatible film barriers as a deterrent to peridural fibrosis were evaluated in an ovine laminectomy model. It discusses that all 3 products found to be safe with the lactide/caprolactone product determined to be superior in efficacy.

Abstract: Responses of dorsal spinal cord blood flow (SCBF) to innocuous mechanical cutaneous stimulation were investigated in anesthetized central nervous system intact (CNS-intact) and C2 spinalized rats. SCBF was recorded at the L4–L6 level with a laser Doppler flowmeter. SCBF increased with brushing of the ipsilateral proximal hindlimb and hindpaw, and there were no significant differences in the magnitudes of the responses in CNS-intact and spinalized animals. Brushing of the lower back had no effect on SCBF at the L4–L6 level in either cohort. Brushing stimulation produced no significant changes in systemic arterial blood pressure. The responses of SCBF to brushing in CNS-intact animals were diminished by pretreatment with phenoxybenzamine, an alpha-adrenoceptor blocking agent, but no such effects were seen in spinalized animals. These results indicate that innocuous mechanical cutaneous input can produce a segmentally-organized increase in regional SCBF, and that the responses are modulated, in part at least, by alpha-adrenergic receptors via supraspinal structures. [Copyright &y& Elsevier]

Abstract: In urethane-anesthetized, artificially-ventilated rats, alterations in dorsal spinal cord blood flow (SCBF) were measured with a laser Doppler flowmeter in response to innocuous mechanical cutaneous stimulation. SCBF recorded at the T12-L1 level increased with brushing of the ipsilateral, but not contralateral, upper back, lower back or proximal hindlimb. Brushing of the forepaw, proximal forelimb or hindpaw had no effect on T12-L1 SCBF. SCBF recorded at the L4-6 level increased with brushing of the ipsilateral, but not contralateral, proximal hindlimb and hindpaw. Brushing of the forepaw, proximal forelimb, upper back or lower back had no effect on SCBF at the L4-6 level. None of these brushing stimuli produced significant changes in systemic arterial blood pressure or heart rate. Pretreatment with phenoxybenzamine, an alpha adrenoceptor blocking agent, resulted in a small but statistically significant attenuation in the response of SCBF to brushing. However, pretreatment with propranolol, a beta adrenoceptor blocking agent, or atropine, a muscarinic cholinergic receptor blocking agent, produced no such effect. These results indicate that innocuous mechanical cutaneous input can produce a segmentally-organized increase in regional SCBF, which may be mediated in part, by alpha adrenergic receptors. [Copyright &y& Elsevier]

Objectives: The evaluation of the spatial spread of ischemia following spinal cord injury (SCI) is important for planning therapeutic strategies for secondary injury. The purpose of this study was to investigate in detail the change in regional spinal cord blood flow (rSCBF) after SCI. Methods: Thirty-four male Wistar rats were used, for which laminectomies of the T11–13 vertebrae were performed. SCI was produced by a directed impact through a laminectomy site at the level of the Th12 using a pneumatic impact device. We measured the sequential and spatial changes of rSCBF using a laser Doppler scanning technique before and after SCI in rats not only at the injured myelomere but also at the circumferent myelomeres. SCBF mapping was carried out before and after SCI on each site. Results: After SCI, the rSCBF value gradually decreased for each site for the SCI group (n=26), while it globally decreased at the epicenter. Moreover, a decrease in SCBF was observed at the caudal and rostral sites. The mean value of the %SCBF 120 minutes after SCI for each site was 63.6±2.3% (Th11), 74.4±4.5% (Th12), 75.8±3.2% (Th13), and was significantly lower for the rostral site compared with the caudal site (p<0.05, one-way analysis of variance). Discussion: This study found that SCBF is significantly decreased not only at the injured myelomere but also at the circumferent myelomeres. Circumferentially extending ischemia after SCI is related to secondary injury after SCI. The improvement in SCBF after SCI, therefore, can be attributed to the treatment of SCI. [ABSTRACT FROM AUTHOR]

Adenosine and adenosine analogues induce antinociception both after systemic and intrathecal (i.t.) administration in animal models. Further, patients with neuropathic pain have been treated successfully with i.t. adenosine. Prior to introducing new analgesic drugs for regular spinal use in humans, experimental studies must be undertaken to evaluate the risks of neurotoxicity. It is important to evaluate the possibility of cytotoxic effects and that antinociception may be due to decreased spinal cord blood flow (SCBF) and neural ischaemia. The present study evaluates whether adenosine or isotonic mannitol induces changes in SCBF as assessed by laser-Doppler flowmetry (LDF).After laminectomy and insertion of i.t. catheters, seven rats received adenosine 50 μg in isotonic mannitol 500 μg, six rats received isotonic mannitol 500 μg and eight rats received saline 0.9%. SCBF was registered by the LDF technique continuously for 3 h after injection. Arterial blood pressure was also assessed.In the adenosine in mannitol group, SCBF increased up to 230% of baseline levels for almost 40 min,P = 0.044 and then declined. In the mannitol group, SCBF increased up to 180% of baseline (P < 0.011) before declining. At 60 min, SCBF had returned to saline levels and remained stable during the rest of the experiment.Intrathecal administration of adenosine in mannitol and of mannitol both increased SCBF in rats, compared with saline. It is unlikely that the effects on SCBF induced by adenosine and mannitol could result in neurotoxicity of the spinal cord. [ABSTRACT FROM AUTHOR]

A number of previous studies indicated that ischemia–reperfusion injury causes two distinct types of cell death—necrosis and apoptosis—in the central nervous system. It was also implicated that the intensity of injury can somehow affect the cell death mechanisms. By occluding the descending thoracic aorta with or without simultaneously induced hypovolemic hypotension in rats, we established a model of experimental spinal cord ischemia–reperfusion (I/R) in which the injury severity can be controlled. Recordings of carotid blood pressure (CBP) and spinal cord blood flow (SCBF) showed that aortic occlusion induced dramatic CBP elevation but SCBF drop in both the normotensive (NT) and hypotensive (HT) groups of rats. However, the HT group demonstrated significantly lower SCBF during aortic occlusion, and much slower elevation of SCBF after reperfusion, and extremely poor neurological performance. Spinal cord lesions were characterized by infarction associated with extensive necrotic cell death, but little apoptosis and caspase-3 activity. In contrast, in the NT group, I/R injury resulted in minor tissue destruction associated with persistent abundant apoptosis, augmented caspase-3 activity, and favorable functional outcome. The relative sparing of motoneurons in the ventral horns from apoptosis might have accounted for the minor functional impairment in the NT group. The severity of I/R injury was found to have substantial impact on the histopathological changes and cell death mechanisms, which correlate with neurological performance. Our results implicate that injury severity and duration after injury are two critical factors to be considered in therapeutic intervention. [Copyright &y& Elsevier]

The systemic treatment effects of OP-1206 α-CD (17S-20-dimethyl-trans-delta 2-PGE1 alpha-cyclodextrin clathrate), a prostaglandin E1 (PGE1) analogue, on walking dysfunction, spinal cord blood flow (SCBF) and skin blood flow (SKBF) were assessed in the rat neuropathic intermittent claudication (IC) model in comparison with nifedipine (dimethyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate), ticlopidine (5-[(2-chlorophenyl)methyl]-4,5,6,7-tetrahydrothieno[3,2-C]pyridine hydrochloride) and cilostazol (6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-quinolinone). Two pieces of silicone rubber strips were placed in the lumbar (L4 and L6) epidural space in rats. After surgery, walking function was measured using a treadmill apparatus. SCBF and SKBF were measured using a laser-Doppler flow meter. Drugs were administered orally twice a day for 11 days from day 3 post-surgery. Treatment with OP-1206 α-CD significantly improved walking dysfunction on days 5, 7 and 14, and improved SCBF on day 14 post-surgery. SKBF remained unaffected. Treatment with nifedipine, ticlopidine or cilostazol had no significant effects on any of the parameters measured in this model. These data suggest that the therapeutic effect of OP-1206 α-CD is primarily mediated by the improved local SCBF at the territory of spinal stenosis and not due to improvement of peripheral perfusion and/or antiplatelet activity. [Copyright &y& Elsevier]