Arterial pulsation-dependent perivascular cerebrospinal fluid flow into the central canal in the sheep spinal cord

The impetus for the enlargement of syringes is unknown. The authors hypothesize that there is a flow of cerebrospinal fluid (CSF) from perivascular spaces into the central canal and that the flow is driven by arterial pulsations. Using horseradish peroxidase as a tracer, the CSF flow was studied in normal sheep, in sheep with damped arterial pulsations, and in sheep with lowered spinal subarachnoid pressure. The CSF flow from perivascular spaces into the central canal was demonstrated in the normal sheep, and two patterns of flow were identified: 1) from perivascular spaces in the central gray matter; and 2) from perivascular spaces in the ventral white commissure. Flow into the central canal was also observed in the sheep with lowered spinal subarachnoid pressure, but not in those with reduced arterial pulse pressure. This study provides evidence that CSF flow from perivascular spaces into the central canal is dependent on arterial pulsations. Arterial pulsation-driven CSF flow may be the impetus for the expansion of syringes.     

Effects of spinal cord ischemia on evoked potential recovery and postischemic regional spinal cord blood flow

The effects of spinal cord ischemia on spinal cord blood flow (SCBF) and somatosensory (SSEP) and motor (MEP) evoked potentials were investigated in a rabbit model of reversible spinal cord ischemia. Spinal cord ischemia was produced by balloon occlusion of the infrarenal aorta for 30, 60, and 90 min. SCBF, SSEPs, and MEPs were measured before, during, and 1 h after aortic occlusion. Aortic occlusion produced absolute ischemia of the caudal cord followed by hyperemia upon reperfusion. SSEP's and MEP's were obliterated during ischemia but demonstrated gradual albeit incomplete recovery following reperfusion with amplitude recovery inversely proportional to the duration of ischemia. Later peaks were more severely affected by a given period of ischemia than were early waves. In general, SSEP's were more resistant to ischemia than were MEP's although the differences were not significant.     

Effect of intrathecal nimodipine on spinal cord blood flow and evoked potentials in the normal or injured cord

A method was developed for administering intrathecal pharmacotherapy in a rat model of spinal cord injury. The effects of intrathecal administration of nimodipine on spinal cord blood flow (SCBF) and evoked potentials (EPs) were measured in the normal and injured spinal cord. It had previously been shown that systemic nimodipine caused severe hypotension after spinal cord injury. After baseline SCBF and EPs, 15 uninjured rats were blindly allocated to one of three groups: one placebo group (n = 5); and two groups with intrathecal nimodipine, 0.05 mg/kg (n = 5), or 0.2 mg/kg (n = 5). Ten other rats received a 35 g acute clip compression injury of the spinal cord for 1 minute and, were allocated to one of two groups: placebo (n = 5); and intrathecal nimodipine 0.05 mg/kg (n = 5) given 60 min after injury. In the uninjured groups, neither 0.05 nor 0.2 mg/kg of nimodipine increased SCBF during, or 30 min after, intrathecal infusion. However, the mean arterial blood pressure (MABP) decreased significantly to 69.73.1% after the infusion of 0.2 mg/kg nimodipine and did not recover by 98 min. In all three groups of uninjured rats, the amplitude of the cerebellar EP was decreased 30 min after infusion. After spinal cord injury, there were significant decreases in MABP, SCBF and EP amplitude in both placebo and treatment groups, but there was no therapeutic benefit from nimodipine. Thus, intrathecal infusion of nimodipine did not prevent the hypotension encountered with systemic administration and exerted no beneficial effect on SCBF or EPs after acute spinal cord injury.     

Regional spinal cord blood flow in rats after severe cord trauma

Spinal cord blood flow (SCBF) was measured in 12 albino rats following acute cord injury produced by the extradural clip compression technique. Severe injury was produced with the clip compressing the cord with a force of 180 gm for 5 minutes, an injury previously shown to produce a severe functional deficit. Regional SCBF was measured 15 minutes, 2 hours, and 24 hours after injury by the 14C-antipyrine autoradiographic technique and a scanning microscope photometer. At 15 minutes and 2 hours, white and gray matter blood flow was severely diminished, and, at 24 hours, there was only minimal improvement. Focal decreases in blood flow were seen in white and gray matter for a considerable distance proximal and distal to the site of cord trauma. Thus, it has been confirmed in this model that severe cord compression injury produces severe posttraumatic ischemia in the cord which lasts for at least 24 hours.     

Effects of distraction on physiologic integrity of the spinal cord, spinal cord blood flow, and clinical status

The authors determined the effects of distraction of the spine on physiologic integrity of the spinal cord using neurogenic motor evoked potentials (NMEPs), somatosensory evoked potentials (SEPs), spinal cord blood flow measurements, and clinical status in nine hogs. Spinal cord blood flow was measured after each level of distraction using the hydrogen washout technique. The results indicated that blood flow of at least 65% of baseline was required to maintain physiologic integrity of the spinal cord, and that a decrease of blood flow to 12% of baseline was associated with paraplegia. Neurogenic motor evoked potentials always correlated with the animal's postsurgical clinical status, whereas the SEP was falsely negative in one animal.     

Simultaneous recording of cerebrospinal fluid pressure and middle cerebral artery blood flow velocity in patients with suspected symptomatic normal pressure hydrocephalus

Whether anaphylactic histamine release from rat peritoneal mast cells is influenced by betahistine, a histamine H1-receptor agonist/H3-antagonist, and dimaprit, an H2-agonist, was examined. Treatment with dimaprit at 6 and 60 microM for 20 min significantly inhibited the anaphylactic histamine release, whereas betahistine at up to 80 microM under the same conditions did not affect it. Treatment with dimaprit at 6 and 60 microM for 1 to 20 min and for 5 to 20 min, respectively, caused a time-dependent inhibition of the release, but up to 30 min treatment with 8 and 80 microM betahistine had no effect. The decreased histamine release induced by dimaprit was recovered by neither mepyramine nor cimetidine. However, thioperamide, an H3-selective antagonist, dose-dependently restored the diminished release. From these results, the inhibition of anaphylactic histamine release by dimaprit is not produced by the stimulation of H2-receptors, but involves the stimulation of H3-like receptors or H3-subtype receptors, which are distinct from the H3-receptors located in brain, and suggests that the receptor plays an important role in the negative feedback regulation of histamine release.     

Effect of sudden decompression on tissue pressure in the brain and the cerebrospinal fluid pressure

Extracranial hypertension was produced in cats by means of epidural compression with a baloon. After 2 hours of compression sudden decompression was performed and tissue pressure was compared at symmetrical sites of cerebral hemispheres with cerebrospinal fluid pressure measured in the cisterna magna. It was found that symmetrical tissue pystem, which was due probably to early oedema developing in the compressed area.     

Effects of blood contamination on cerebrospinal fluid analysis

Data were obtained from 190 cerebrospinal fluid samples collected from both clinically normal and diseased dogs, cats, cows, and horses. Red blood cells, indicating blood contamination, were identified in 115 samples. White blood cells were a rare finding in normal animals. Blood contamination appeared to have little effect on white blood cell numbers even though, in several samples, thousands of red blood cells were identified. An accepted formula to correct for blood contamination was found to be an unreliable method to determine "uncontaminated" values for white blood cells, total protein, or creatine phosphokinase.     

Special dendritic and axonal endings formed by the cerebrospinal fluid contacting neurons of the spinal cord

The cerebrospinal fluid (CSF) contacting neurons have a dendritic process which protrudes into the central canal, and is provided with one long kinocilium and many shorter stereocilia (about 80 in the turtle) as revealed by scanning electron mecroscopy. The shape, number and arrangement of the cilia are similar to those of known receptor endings. The silver impregnated axons of these cells converge to a paired centrosuperficial tract forming terminal enlargements at the ventrolateral surface of the spinal cord. Lying among glial endfeet these terminals are ultrastructurally similar to those present in known neurosecretory areas. The nerve endings are attached to the basal lamina, and they comprise many synaptic vesicles (200 to 400 A in diameter), as well as granular vesicles of different sizes (diameter 600 to 1800 A). The axons may lie within finger-like protrusions on the surface of the spinal cord, or they may terminate around vesseles. Morphological evidence suggests that these nerve terminals and the corresponding CSF contacting perikarya represent a spinal neurosecretory system possibly influenced by information taken up by its special dendrites protruding into the inner CSF space.     

Effect of pressure on transmural fluid flow in different de-endothelialised arteries

This experiment was carried out with these rats were injected with 3.8 microliters (19 micrograms) convulsive dosage of coriaria lactone (CL) in the left cerebral motor cortex of the forelimb to induce acute focal epilepsy, while the other 5 rats as controls (no seizure) received normal saline solution of the same volume and at the same location. The brains were taken after seizuring for 60 min. The volume (water displacement method) and weight of the brain were measured. The brain was cut coronally and the structures of hippocampus were compared morphologically with those of the pair-matched control. The area of hippocampal formation was measured with paraffin section by test grid under 40x. The mean size (Feret's diameter) of pyramidal neurons in CA1 region was measured with semithin section by ocular micrometer under 1000x. The areal fraction of several organelles of the CA1 pyramidal cells was measured with EM negative film by magnifier. Under conditions of the consistent reference space, especially the size of CA1 pyramidal cells, the areal fraction of rough endoplasmic reticulum, lysosome and mitochondria increased significantly (P < 0.05) in epileptic rats. It indicated that their volume increased. The results show that certain ultrastructural changes have taken place after seizuring for 60 min.     

Alteration of thromboxane A2/prostacyclin and their effect on spinal cord blood flow in experimental spinal cord injury in rats

In order to document the contribution of Thromboxane (TXA2) and Prostacyclin (PGI2) to the secondary damage following spinal cord injury (SCI) and their effects on spinal cord blood flow (SCBF), the alteration of SCBF, TXB2 and 6-keto-PGF1 alpha concentration in injury site (T13-L1) and adjacent cords (upper: T12, under: L2) were studied using a rat SCI model induced by Allen's weight drop method (50g-cm). The result showed that after SCI the SCBF in injury site significantly reduced during 1-2 hrs and reduced further during 4-8 hrs. The SCBF in adjacent cords also decreased during 4-8 hrs. TXB2 levels significantly increased at 1 hr and reached peak value at 4 hrs. The 6-keto-PGF1 alpha concentration also significantly increased at 1 hr and maintained that level for 24 hrs. The TXB2/6-keto-PGF1 alpha ratio was significantly elevated at 1 hr and reached its peak at 4 hrs after SCI, then gradually decreased to the preinjury level during 8-24 hrs. The negative correlation of SCBF with TXB2 concentration and TXB2/6-keto-PGF1 alpha ratio were appeared. The experimental results indicated that the imbalance of TXB2/6-keto-PGF1 alpha could be the main cause of microcirculatory disturbance and secondary damage in SCI.     

Regional cerebral blood flow and cerebrospinal fluid amino acid analysis in elderly dementia

Regional cerebral blood flow and amino acid concentration in the cerebrospinal fluid were studied in 12 cases of vascular dementia, 12 cases of Alzheimer's disease, 12 cases of chronic alcoholism, and 12 age-matched healthy controls. In vascular dementia, blood flows were decreased in the cerebral cortex, frontal white matter, thalamus, caudate nucleus, and putamen and alpha-aminobutyric acid and glutamic acid concentrations were increased in the cerebrospinal fluid. In Alzheimer's disease, blood flows were decreased in the frontal cortex, parietal cortex, temporal cortex, and frontal white matter and alanine concentration was increased in the cerebrospinal fluid. In chronic alcoholism, blood flows were decreased in the cerebral cortex, thalamus, and putamen and urea, alanine, and glycine concentrations were increased in the cerebrospinal fluid.     

Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension

Spinal cerebrospinal fluid (CSF) leaks are often implicated as the cause of the syndrome of spontaneous intracranial hypotension, but they have rarely been demonstrated radiographically or surgically. The authors reviewed their experience with documented cases of spinal CSF leaks of spontaneous onset in 11 patients including their surgical observations in four of the patients. The mean age of the six women and five men included in the study was 38 years (range 22-51 years). All patients presented with a postural headache; however, most had additional symptoms, including nausea, emesis, sixth cranial-nerve paresis, or local back pain at the level of the CSF leak. All patients underwent indium-111 radionucleotide cisternography or computerized tomographic (CT) myelography. The location of the spontaneous CSF leak was in the cervical spine in two patients, the cervicothoracic junction in three patients, the thoracic spine in five patients, and the lumbar spine in one patient. The false negative rate for radionucleotide cisternography was high (30%). Subdural fluid collections, meningeal enhancement, and downward displacement of the cerebellum, resembling a Chiari I malformation, were commonly found on cranial imaging studies. In most patients, the symptoms resolved in response to supportive measures or an epidural blood patch. Leaking meningeal diverticula were found to be the cause of the CSF leak in four patients who underwent surgery. In three patients these diverticula could be ligated with good result but in one patient an extensive complex of meningeal diverticula was found to be inoperable. Two patients had an unusual body habitus and joint hypermobility, and two other patients had suffered a spontaneous retinal detachment at a young age. In conclusion, spontaneous spinal CSF leaks are uncommon, but they are increasingly recognized as a cause of spontaneous intracranial hypotension. Most spinal CSF leaks are located at the cervicothoracic junction or in the thoracic spine, and they may be associated with meningeal diverticula. The radiographic study of choice is CT myelography. The disease is usually self-limiting, but in selected cases our experience with surgical ligation of leaking meningeal diverticula has been satisfactory. An underlying connective tissue disorder may be present in some patients with a spontaneous spinal CSF leak.     

Viscoelastic relaxation and regional blood flow response to spinal cord compression and decompression

STUDY DESIGN: To better understand the relationships between primary mechanical factors of spinal cord trauma and secondary mechanisms of injury, this study evaluated regional blood flow and somatosensory evoked potential function in an in vivo canine model with controlled velocity spinal cord displacement and real-time piston-spinal cord interface pressure feedback. OBJECTIVES: To determine the effect of regional spinal cord blood flow and viscoelastic cord relaxation on recovery of neural conduction, with and without spinal cord decompression. SUMMARY OF BACKGROUND DATA: The relative contribution of mechanical and vascular factors on spinal cord injury remains undefined. METHODS: Twelve beagles were anesthetized and underwent T13 laminectomy. A constant velocity spinal cord compression was applied using a hydraulic loading piston with a subminiature pressure transducer rigidly attached to the spinal column. Spinal cord displacement was stopped when somatosensory evoked potential amplitudes decreased by 50% (maximum compression). Six animals were decompressed 5 minutes after maximum compression and were compared with six animals who had spinal cord displacement maintained for 3 hours and were not decompressed. Regional spinal cord blood flow was measured with a fluorescent microsphere technique. RESULTS: At maximum compression, regional spinal cord blood flow at the injury site fell from 19.0 +/- 1.3 mL/100 g/min to 12.6 +/- 1.0 mL/100 g/min, whereas piston-spinal cord interface pressure was 30.5 +/- 1.8 kPa, and cord displacement measured 2.1 +/- 0.1 mm (mean +/- SE). Five minutes after the piston translation was stopped, the spinal cord interface pressure had dissipated 51%, whereas the somatosensory evoked potential amplitudes continued to decrease to 16% of baseline. In the sustained compression group, cord interface pressure relaxed to 13% of maximum within 90 minutes; however, no recovery of somatosensory evoked potential function occurred, and regional spinal cord blood flow remained significantly lower than baseline at 30 and 180 minutes after maximum compression. In the six animals that underwent spinal cord decompression, somatosensory evoked potential function and regional spinal cord blood flow recovered to baseline 30 minutes after maximum compression. CONCLUSIONS: Despite rapid cord relaxation of more than 50% within 5 minutes after maximum compression, somatosensory evoked potential conduction recovered only with early decompression. Spinal cord decompression was associated with an early recovery of regional spinal cord blood flow and somatosensory evoked potential recovery. By 3 hours, spinal cord blood flow was similar in both the compressed and decompressed groups, despite that somatosensory evoked potential recovery occurred only in the decompressed group.     

Neurokinin-1 receptors and spinal cord control of blood pressure in spontaneously hypertensive rats

In this study we examined blood pressure and heart rate responses to intrathecal administration of a synthetic NK1-receptor agonist, H2N-(CH2)4-CO-Phe-Phe-Pro-NmeLeu-Met-NH2 (GR 73,632), in spontaneously hypertensive rats (SHR) and their progenitor strain, the Wistar-Kyoto rat (WKY). Sodium pentobarbitone anaesthetised rats with implanted intrathecal catheters were paralysed (pancuronium dibromide) and artificially ventilated. Injection of GR 73,632 at the T9 spinal level evoked dose-dependent increases in mean arterial pressure (MAP) in WKY and SHR. SHR had a lower MAP response threshold than WKY but increase in response with increasing dose was less in SHR than WKY. Biphasic blood pressure responses at high doses were observed in both strains. Prior administration of the NK1-receptor antagonist (3 aR,7aR)-7,7-diphenyl-2-[1-imino-2(methoxyphenyl)ethyl] perhydroisoindol-4-one (RP 67,580) significantly reduced the pressor response in WKY but not SHR. The depressor response was not attenuated in either strain.     

Monitoring of cerebrospinal fluid pressure during embolization of AVM

We experienced that therapeutic embolization of a large cerebral arteriovenous malformation (AVM) led to venous outflow obstruction resulting in intracranial hypertension in a patient who had undergone external decompression. To evaluate hemodynamic changes after embolization, we monitored the cerebrospinal fluid pressure in the next four patients who underwent endovascular treatment. The embolization of a medium AVM resulted in a slight increase in the cerebrospinal fluid pressure. In two medium AVMs, embolization produced slight decreases in the cerebrospinal fluid pressure. In a small AVM, we did not observe any changes in the cerebrospinal fluid pressure during the endovascular treatment. We discuss the mechanism of changes in the intracranial pressure after embolization and conclude that monitoring of the cerebrospinal fluid pressure immediately yields useful information for hemodynamic changes during endovascular treatment.     

Dynamic changes in cerebrospinal fluid pressure during neurosurgical operations

The effects of hyperventilation, osmotic and diuretic agents (urea, frusemide), thiopentone and succinylcholine chloride on the intracranial pressure were studied in neurosurgical patients with brain tumours. We have shown that hyperventilation together with osmotic and diuretic agents is very useful for reducing increased intracranial pressure.     

Effect of spinal cord transection on N-methyl-D-aspartate receptors in the cord

Spinal cord injury can lead to an exaggeration of transmission through spinal pathways, resulting in muscle spasticity, chronic pain, and abnormal control of blood pressure and bladder function. These conditions are mediated, in part, by N-methyl-D-aspartate (NMDA) receptors on spinal neurons, but the effects of cord injury on the expression or function of these receptors is unknown. Therefore, antibodies to the NMDA-R1 receptor subunit and binding of [3H]MK-801 were used to assess NMDA receptors in the spinal cord. Receptor density in rats with intact spinal cords was compared to that in rats 1 and 2 weeks after spinal cord transection (SCT) at the mid-thoracic level. At 1 and 2 weeks after SCT, [3H]MK-801 binding was reduced in most laminae in cord segments caudal to the injury, whereas no decrease in amount of R1 subunit immunoreactivity was observed. No significant changes in [3H]MK-801 binding and NMDA-R1 immunoreactivity could be seen rostral to the transection. Since [3H]MK-801 binding requires an open ion channel, the discrepancy between [3H]MK-801 binding and immunocytochemistry may indicate a loss of functional receptors without a consistent change in their total number. Therefore, the exaggerated reflexes that are well established in rats 2 weeks after cord injury must be mediated by a mechanism that withstands attenuation of NMDA receptor function.