The effects of serotonin on local cerebral blood flow

This study was undertaken to measure the effects of serotonin administration on local cerebral blood flow following blood-brain barrier (BBB) disruption with hypertonic urea. Rats were anesthetized with halothane in nitrous oxide and oxygen (70%:30%). In some animals urea (3.5 M) was infused retrogradely through an external carotid catheter, followed after 10 min by serotonin (50 ng kg-1 min-1) or physiological saline. Local cerebral blood flow was measured using the 14C-iodoantipyrine quantitative autoradiographic technique of Sakurada et al. (1978). The administration of saline or urea alone had only minimal effects on local cerebral blood flow. When the BBB was intact, serotonin produced a significant fall in regional blood flow only in the caudate nucleus. Following BBB disruption, however, serotonin produced a marked decrease in local perfusion in a number of discrete brain areas that are supplied by blood from the internal carotid artery. On the other hand, there were increases in local perfusion in areas not supplied by the internal carotid artery.     

Local cooling alters neural mechanisms producing changes in peripheral blood flow by spinal cord stimulation

This study was performed to investigate the respective role of sensory afferent and sympathetic fibers in peripheral vasodilatation induced by spinal cord stimulation at different hindpaw skin temperatures. Cooling the skin was used as a strategy to enhance sympathetic activity [Am. J. Physiol.: Heart Circ. Physiol. 263 (1992) H1197]. Cutaneous blood flow in the footpad of anesthetized rats was recorded using laser Doppler flowmetry. Local cooling (<25 degrees C) or moderate local cooling (25-28 degrees C) of the hindpaw was produced with a cooling copper coil. Spinal cord stimulation delivered at clinically relevant parameters and with 30%, 60%, and 90% of motor threshold induced the early phase of vasodilatation in the cooled and the moderately cooled hindpaw. In addition, spinal cord stimulation at 90% of motor threshold produced the late phase of vasodilatation only in the cooled hindpaw, which was possible to block by the autonomic ganglion-blocking agent, hexamethonium. The early responses to spinal cord stimulation in the moderately cooled hindpaw were not affected by hexamethonium. In contrast, both the early and the late phase responses were eliminated by CGRP (8-37), an antagonist of the calcitonin gene-related peptide receptor. After dorsal rhizotomy, spinal cord stimulation at 90% of motor threshold elicited hexamethonium-sensitive vasodilatation in the cooled hindpaw (late phase). These results suggest that spinal cord stimulation-induced vasodilatation in the cooled hindpaw (<25 degrees C) is mediated via both the sensory afferent (early phase of vasodilatation) and via suppression of the sympathetic efferent activity (late phase) although the threshold for vasodilatation via the sympathetic efferent fibers is higher than that via sensory nerves. In contrast, vasodilatation via sensory afferent fibers may predominate with moderate temperatures (25-28 degrees C). Thus, two complementary mechanisms for spinal cord stimulation-induced vasodilatation may exist depending on the basal sympathetic tone.     

The effect of sciatic nerve stimulation on spinal cord blood flow.

Focal spinal cord blood flow was measured in the left dorsal column during left sciatic nerve stimulation, and compared to blood flow in the same area during sciatic nerve inactivity. Blood flow was found to be significantly increased during stimulation. It is suggested that this increased blood flow is a reflection of increased metabolic demands of the neurons and synaptic systems within the internuncial neural pools, activated by stimulation of all components of the sciatic nerve, rather than a reflection of increased non-synaptic axonal conduction in the dorsal column.     

Spinal cord compression and blood flow. I. The effect of raised cerebrospinal fluid pressure on spinal cord blood flow

The effect of cerebrospinal fluid pressure (CSFP) on spinal cord blood flow (SCBF), measured by the hydrogen clearance technique, was studied in dogs. CSFP was altered by the infusion of mock CSF into the lumbar subarachnoid space. Occluding snares at T-13 limited the effect of raised pressure on the brain. As the perfusion pressure was reduced when the CSFP was increased, flow remained constant up to a perfusion pressure of approximately 50 mm Hg. Below this value, flow decreased with decreasing perfusion pressure. Normal flow values could be reestablished even at a raised CSFP if the perfusion pressure was increased by raising the arterial blood pressure. Rapid reduction of CSFP was accompanied by reactive hyperemia. The autoregulation of flow down to a perfusion pressure of 50 mm Hg was due to progressive decrease in vascular resistance. Carbon dioxide-responsiveness of the vessels was decreased markedly as the perfusion pressure was reduced.     

Blocking weight-induced spinal cord injury in rats: effects of TRH or naloxone on motor function recovery and spinal cord blood flow

The ability of thyrotropin releasing hormone (TRH) or naloxone to reduce the motor function deficit and to improve the spinal cord blood flow (SCBF) was investigated in a rat spinal cord compression injury model. Spinal cord injury was induced by compression for 5 min with a load of 35 g on a 2.2 x 5.0 mm sized compression plate causing a transient paraparesis. One group of animals was given TRH, one group naloxone and one group saline alone. Each drug was administered intravenously as a bolus dose of 2 mg/kg 60 min after injury followed by a continuous infusion of 2 mg/kg/h for 4 h. The motor performance was assessed daily on the inclined plane until Day 4, when SCBF was measured with the 14C-iodoantipyrine autoradiographic method. It was found that neither TRH nor naloxone had promoted motor function recovery or affected SCBF 4 days after spinal cord injury.     

Relation between spinal cord and epidural blood flow

To test applicability of monitoring regional spinal cord blood flow by measuring regional epidural blood flow, both were simultaneously measured by the hydrogen clearance method in response to changes in PaCO2 and mean arterial blood pressure in rats anesthetized with pentobarbital. An excellent correlation was found between regional spinal and epidural blood flow over a physiological range of PaCO2 (27.8-66.7 torr) and blood pressure (30-130 torr), while a poor correlation was demonstrated between regional spinal or epidural blood flow and regional muscle blood flow in response to these same physiological parameters. Moreover, the rates of change in regional spinal and epidural blood flows were almost the same in response to both PaCO2 and blood pressure. These results suggest that both regional spinal and epidural blood flow are regulated by a similar mechanism and suggest that regional spinal cord blood flow can be monitored by regional epidural blood flow.     

Effect of methylprednisolone on motor function and spinal cord blood flow after spinal cord compression in rats

The effect of methylprednisolone (MP) on neurologic recovery and spinal cord blood flow (SCBF) was investigated up to 4 days after a spinal cord compression injury in rats. The injury was produced at midthoracic level by applying a load of 35 g on a 2.2 x 5.0 mm compression plate for 5 min, which resulted in transient paraparesis. MP was given as a bolus dose of 30 mg/kg i.v. 60 min after injury (n = 20) and controls were given saline (n = 10). The motor performance was assessed daily as the capacity angle on the inclined plane and SCBF was measured by 14C-iodoantipyrine autoradiography on Days 1 or 4. On Day 1 the capacity angle was reduced from about 63 degrees preoperatively to 33 +/- 2 degrees (mean +/- SEM) in the control group and to 50 +/- 1 degrees in the group treated with MP (p less than 0.05). Thereafter there was a slight improvement in both groups, but the difference persisted throughout the observation period. On Day 4 both gray and white matter SCBF was better preserved in MP-treated animals than in the control group (59 +/- 4 versus 49 +/- 3 ml/min/100 g tissue for gray matter and 13.6 +/- 0.6 versus 10.7 +/- 0.8 ml/min/100 g tissue for white matter). Posttraumatic treatment with MP, thus, improved both the neurologic recovery during the first 4 days and SCBF as measured on Day 4. It is speculated that the effect of MP is at least partly exerted on the vascular bed.     

Intraoperative measurement of spinal cord blood flow in syringomyelia

The role of spinal cord ischemia in the pathophysiology of syringomyelia remains undetermined. Previous reports in the literature suggest that shunting of syringes can improve spinal cord blood flow. In order to determine the effects of syrinx decompression on spinal cord blood flow in patients with syringomyelia, we prospectively measured regional spinal cord blood flow (RSCBF) intraoperatively pre and post shunting in patients with symptomatic syringomyelia using laser doppler flowmetry. Six patients with MRI documented syringomyelia were studied (three with Arnold Chiari I malformation and associated syrinx and three with post-traumatic syringomyelia). Surgery was performed on all patients with either a syringopleural or syringoperitoneal shunt. Laser doppler blood flow and somatosensory evoked potentials were monitored prior to myelotomy and after shunt insertion. Results indicate that there was a significant increase in RSCBF after decompression of the syrinx. This study supports the hypothesis that spinal cord ischemia is important in the pathophysiology of syringomyelia and confirms previous reports in the literature regarding RSCBF in syringomyelia.     

Effect of differential spinal cord transection on human cerebral blood flow

Regional cerebral blood flow (rCBF) was measured by ¹³³Xe inhalation in 17 patients with chronic spinal cord transection. This was done to investigate any effects such spinal cord deafferentation might have on resting rCBF and to test whether resulting chronic preganglionic sympathectomy influenced cerebral vasomotor CO₂ responsiveness and autoregulation. Thirteen patients had complete cervical cord transection (CCT) at levels C4–C6 (age 37 ± 15 years, time interval, 2 months–20 years). Four patients had complete thoracic cord transection at levels T3–4, T8 and T12 (TCT; age 49 ± 22 years; time interval 2–5 months). CO₂ responsiveness was tested by induced hypercapnia in 11 patients with CCT and 2 patients with TCT. Autoregulation was tested in 10 patients with CCT and 4 patients with TCT by decreasing cerebral perfusion pressure during postural tilting.Mean resting hemispheric Fg values (MHFg) were significantly reduced only in patients with CCT ($\text{MHFg}\text{=}\text{69 ± 12}\text{ml}\text{100}\text{g brain/min}$), while brain stem-cerebellar Fg values (BSC Fg) were reduced significantly both in patients with CCT (BSC Fg = 85 ± 10) and with TCT (BSC Fg = 88 ± 12) compared to values measured in healthy normals (N = 21, MHFg = 81 ± 10, BSC Fg = 98 ± 10). Hemispheric CO₂ responsiveness showed a trend toward reduction in patients with CCT but this was not statistically significant. Hemispheric autoregulation was significantly impaired in CCT compared to healthy normals but improved with time and rehabilitation.Results are taken to indicate that deafferentation due to cervical cord transection reduces rCBF in both hemispheres and brain stem-cerebellar regions while deafferentation due to thoracic cord transection only reduces brain stem-cerebellar flow. Extracerebral sympathetic innervation plays a role in autoregulation but has less influence on cerebral CO₂ responsiveness.     

Local transcutaneous cooling of the spinal cord in the rat: effects on long-term outcomes after compression spinal cord injury

This study tested efficiency of a novel thermoelectric cooler for local transcutaneous spinal cord cooling. Spinal cord compression was made by epidural balloon inflation at T8-T9 level of the spinal cord. Experimental animals (n=20) were divided into two groups. In the hypothermic group, local cooling started 25 min after spinal cord injury and lasted for 1 h with paravertebral temperature maintained at 28.5 degrees C (+/-0.3). Normothermic group underwent identical procedures, but their temperature was maintained normothermic. The assessment of neurologic recovery was performed once a week during a 4 weeks survival period. After 4 weeks animals were sacrificed and the extent of the spinal cord lesion morphometrically evaluated. There were no statistically significant intergroup differences in BBB scores and preserved volumes of the spinal cord tissue. In consecutive cross-sectional areas, hypothermic animals had significantly more preserved white matter at the cranial periphery of the lesion. It was concluded that mild posttraumatic hypothermia (31.8 degrees C) had some protective effect on tissue loss after spinal cord injury but this effect was not associated with functional improvement.     

Spinal cord blood flow and systemic blood pressure after experimental spinal cord injury in rats

We looked at the relation between systemic arterial blood pressure and recovery from spinal cord injury by inducing both hypertension and hypotension in 25 rats randomly allocated to five equal groups. The rats received no injury, a mild (2.3-g), or a severe (53.0-g) spinal cord injury lasting 1 minute. We used the hydrogen clearance technique to measure spinal cord blood flow at the injury site (T1) and at an adjacent site (C6). Mean systemic arterial blood pressure was either increased with adrenaline or decreased by phlebotomy in 20-mm-Hg intervals except for the severe-injury group, in which the posttraumatic pressure could only be increased with adrenaline. Spinal cord blood flow remained constant in the no-injury group between 81 and 180 mm Hg. After a mild injury, induced moderate hypertension (121-140 mm Hg) improved spinal cord blood flow significantly, whereas hypotension decreased it in a linear fashion. Severe injury caused a marked decrease in spinal cord blood flow and mean systemic arterial blood pressure. Even extreme hypertension (161-180 mm Hg) induced by adrenaline did not significantly increase spinal cord blood flow at T1 but caused hyperemia at C6 due to loss of autoregulation. In conclusion, normotension should be attempted, irrespective of the severity of spinal cord injury. Induced hypertension after severe spinal cord injury was not beneficial in improving spinal cord blood flow at the injury site while potentially increasing hemorrhage and edema.     

缺血预适应后脊髓区域血流的改变及其对脊髓功能的保护作用

目的：探讨缺血预适应对脊髓区域血流的影响及其对脊髓功能的保护作用。方法：采用放射介入球囊栓塞方法建立脊髓缺血动物模型，氢去除电极测定脊髓区域血流，脊髓诱发电位监测脊髓功能，研究缺血预适应对脊髓缺血的保护作用。结果：缺血预适应５分钟后，脊髓局部区域血流升高，是脊髓诱发电位改变的直接原因；而脊髓区域血流的改变，可能与缺血预适后，儿茶酚胺类神经递质含量轻度升高有关。脊髓不可逆缺血损害后，单胺类递质（ＮＥ，ＤＡ，５－ＨＴ）的严重升高，将造成脊髓血管痉挛、内皮细胞裂隙、多灶出血、坏死，而使脊髓功能受损。脊髓区域血流与脊髓功能的改变密切相关；缺血预适应后，脊髓区域血流的轻度升高以及再次不可逆缺血（３０分钟缺血）后脊髓区域血流的明显改善，是缺血预适应对脊髓功能保护作用的直接原因。结论：缺血预适应可改变脊髓区域血流，增加长时间不可逆缺血后脊髓区域血流并对不可逆脊髓缺血后的脊髓功能损害有明显而确定的保护作用。     

The relationships among the severity of spinal cord injury, motor and somatosensory evoked potentials and spinal cord blood flow

To characterize the changes in axonal function in the motor and somatosensory tracts of the cord after spinal cord injury (SCI) and to correlate these changes with spinal cord blood flow (SCBF), the relationships among the severity of SCI, motor and somatosensory evoked potentials (MEPs and SSEPs) and SCBF were examined. Fifteen rats received a 1.5 g (n = 5), 20 g (n = 5) or 56 g (n = 5) clip compression injury of the cord at C8. SCBF at the injury site was measured by the hydrogen clearance technique 35 min before and 30 min after SCI. Concomitantly MEPs from the cord at T10 (MEP-C) and from the sciatic nerve (MEP-N) and SSEPs were recorded. A linear relationship (r = -0.89, P less than 0.002) was found between the severity of SCI and the reduction in SCBF at the injury site. Linear discriminant analysis revealed that both the MEP (P less than 0.0001) and SSEP (P less than 0.003) were significantly related to the severity of SCI. Furthermore, the amplitude of the MEP (r = 0.65, P less than 0.0001) and SSEP (r = 0.58, P less than 0.001) was significantly correlated with the posttraumatic SCBF. Multiple regression revealed that both the severity of cord injury and the degree of posttraumatic ischemia were significantly related to axonal dysfunction after SCI. While the MEP was more sensitive to injury than the SSEP, the SSEP more accurately distinguished between mild and moderate severities of cord injury. Axonal conduction in the motor and somatosensory tracts of the cord was significantly correlated with the reduction in posttraumatic SCBF and, therefore, these data provide quantitative evidence linking posttraumatic ischemia to axonal dysfunction following acute cord injury. Furthermore, this study validates the hypothesis that the combined recording of MEPs and SSEPs is an accurate technique to assess the physiological integrity of the cord after injury.     

The effects of spinal cord trauma on myelin

Experimental spinal cord trauma was produced in rats by dropping a 10-g weight from a height of 30 cm upon exposed spinal cord. The histological lesion consisted of edema, necrosis, and hemorrhage. The fine structure of the early traumatic lesion (4 to 12 hours) included granular dissolution of axons and a characteristic vesiculation of myelin. The predominant ultrastructural features of older lesions (12 to 72 hours) were intra-axonal calcification and lipid-laden macrophages. The yield of myelin and the activity of adenosine 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) were reduced by approximately 15% at 4 hours and by 60% at 72 hours. Losses in all myelin proteins were observed, but were most severe and occurred earliest in the basic proteins. The ultrastructural and biochemical alterations observed in this study indicate that proteinase activity is increased and may be partially responsible for the traumatic myelinolysis in experimental spinal cord trauma.     

Spinal cord blood flow measured with microspheres following spinal cord injury in the rat

A decrease in spinal cord blood flow (SCBF) is a known sequela of spinal cord injury. The radioactive microsphere technique permits repeated measurement of spinal cord blood flow (SCBF) and cardiac output (CO) in the same experimental animal. The purpose of this study was to adapt the radioactive microsphere technique for use in the rat extradural clip compression injury model used in our laboratory. Thirteen adult Wistar rats were anaesthetized and ventilated. Mean systemic arterial pressure (MSAP) was recorded continuously. Control animals (n = 8) did not have a surgical procedure whereas the injured animals (n = 5) underwent a C7-T1 laminectomy followed by a one minute, 50 gram extradural clip compression injury at T1. Radioactive microspheres were used for two blood flow and CO determinations in both groups. MSAP fell 59% in the injured animals (p less than 0.01), but this was not accompanied by significant changes in heart rate or CO. There was a 50% reduction in SCBF in the injured cord (p less than 0.02), and there were significant reductions in cerebral blood flow (p less than 0.05) and cerebellar blood flow (p less than 0.02) following spinal cord injury.     

Effect of stimulation of the dorsal aspect of the cervical spinal cord on local cerebral blood flow and EEG in the cat

Currently there is considerable interest in electrical stimulation of the dorsal aspect of the cervical spinal cord as a potentially effective therapy for persistent vegetative patients. The authors assessed change in the local cerebral blood flow (LCBF) and electroencephalogram (EEG) in the cat following spinal cord stimulation (SCS). In 31 adult cats under isoflurane anesthesia, an electrode for SCS was introduced epidurally to the midline of the C2-C3 segment. Stimulation was performed at 25 Hz and 0.1 msec for 30 min. These animals were divided into five groups by the voltage: (1) 2V (n = 7), (2) 4V (n = 7), (3) 6V (n = 7), (4) 4V with intravenous injection of muscarinic cholinergic agents--atropine sulfate (n = 5), and (5) sham-operated control (n = 5) without stimulation. LCBF was measured by laser Doppler flowmetry through bilateral small burr holes at the parietal area during and 60 min after stimulation. At 2V, LCBF increased only during SCS, then returned to the pre-stimulated level, while the increase continued until the end of the experiment at 4V and 6V. The increase in LCBF was not affected by atropine sulfate. EEG showed spike and wave or polyspikes after SCS in two animals of the 6V group, but not in the 2V and 4V groups, and moreover a moderate increase of the background activity at only 4V. The present data suggested that SCS at 4V can provide the appropriate microcirculatory enhancement with less harmful influence which continues to increase 30 min after SCS, although the exact mechanism should be elucidated continuously. Within the limitation of animal experiments, this study could provide the logical basis for determining the condition of SCS.     

A precise and sensitive method for measurement of spinal cord blood flow

Spinal cord blood flow can be accurately and rapidly measured in rabbits by intravenous injection of [¹⁴C]iodoantipyrine, collection of sequential arterial samples, and abrupt termination of blood flow to the spinal cord by severing the aorta with a previously implanted ligature. The radioactive tracer concentrations in arterial and spinal cord samples can be rapidly measured in a scintillation counter. The spinal cord blood flow can then be calculated from these blood and tissue tracer concentrations. This method is suitable for use in anesthetized or unanesthetized small animals.