Gross-total hematoma removal of hypertensive basal ganglia hemorrhages: a long-term follow-up.

BACKGROUND AND PURPOSE: Hypertensive basal ganglia hemorrhage (HBGH) accounts for 35%-44% of cases of hypertensive intracranial hemorrhage (ICH), which is one of the most devastating forms of cerebrovascular disease. In this study, intracerebral hematoma was evacuated with a burr hole craniectomy. The relationships of residue hematoma volume to brain edema, inflammation factors and the long-term prognosis of HBGH patients were studied. METHODS: One hundred and seventy-six patients with HBGH were randomly divided into gross-total removal of hematoma (GTRH) and sub-total removal of hematoma (STRH) groups. The pre-operative and post-operative data of the patients in the two groups were compared. The pre-operative data included age, sex, hematoma volume, time from the ictus to the operation, Glasgow Coma Scale (GCS) scores, and the European Stroke Scale (ESS) scores. The post-operative information included edema grade, level of thromboxane B2 (TXB2), 6-keto-prostaglandin F1a (6-K-PGF1a), tumor necrosis factor-a (TNF-a) and endothelin (ET) in hematoma drainage or cerebral spinal fluid (CSF), ESS and Barthel Index (BI). RESULTS: There was no statistical difference between the two groups (P>0.05) in the pre-operative data. The levels of TXB2, 6-K-PGF1a, TNF-a and ET in the GTRH group were significantly lower than those in the STRH group at different post-operative times. The ESS in the GTRH group increased rapidly after the operation and was higher than that in the STRH group. There was a significant difference between the two groups (P<0.05). The post-operative CT scan at different times showed that the brain edema grades were better in the GTRH group than in the STRH group. The BI was higher in the GTRH group than in the STRH group (P<0.05). CONCLUSIONS: GTRH is an effective method to decrease ICH-induced injury to brain tissue. Such effect is related to decreased perihematomal edema formation and secondary injury by coagulation end products activated inflammatory cascade.

Clinical implication of the changes of cAMP, TXA2 and PGI2 in CSF of asphyxiated newborns.

To evaluate the changes of 3', 5'-cyclic adenosine monophosphate (cAMP), thromboxane A2(TXA2) and prostacyclin (PGI2) in cerebrospinal fluid (CSF) in the asphyxiated newborn and explore their roles in hypoxic-ischemic brain damage (HIBD). Thirty-six full term newborns were divided into 3 groups, including 12 with moderate-severe hypoxic-ischaemic encephalopathy (HIE), 13 with mild HIE, 11 without HIE (control group). The levels of cAMP, TXB2 (TXA2 metabolite) and 6-keto-PGF1 alpha (PGI2 metabolite) in CSF and plasma were measured 36-72 h after birth by RIA, and the concentrations were expressed as nM/L (cAMP), ng/L(TXB2 and 6-keto-PGF1 alpha). The infants were followed-up at 6 and 12 month of age and Mental Development Index (MDI) and Psychomotor Development Index (PDI) were measured using Bayley Scales of Infant Development (BSID). The CSF cAMP level in moderate-severe HIE group was 8.60 +/- 2.40, significantly lower than that of the mild HIE group (14.83 +/- 2.84) and the control group (24.43 +/- 2.39) (for both P < 0.01). The levels of TXB2 and 6-keto-PGF1 alpha in CFS in the moderate-severe HIE group (206.06 +/- 29.74, 168.47 +/- 23.02, respectively) were significantly higher than in the mild HIE group (83.37 +/- 28.57, 131.42 +/- 16.57, respectively, P < 0.01) and the control group (41.77 +/- 21.58, 86.23 +/- 13.05, respectively, P < 0.01). The level changes of cAMP, TXB2 and 6-keto-PGF1 alpha in plasma in all groups were similar to those in CSF, but no significant difference was found between mild HIE group and the control group (P > 0.05). The follow-up results showed that MDI and PDI of the moderate-severe HIE group were the lowest (84.79 +/- 13.34, 83.50 +/- 13.28, respectively), followed by mild HIE group (102.19 +/- 7.02, 99.94 +/- 9.08, respectively), with the control group being the highest (116.63 +/- 12.08, 116.69 +/- 10.87, respectively). Univariate analysis showed some significant difference (the moderate-severe HIE group vs. the mild HIE group or the control group, P < 0.01; the mild HIE group vs. the control group P < 0.05). The results suggested that the concentration of cAMP, TXA2 and T/K ratio in CSF after neonatal asphyxia might be sensitive markers in evaluating the severity of brain damage in early stage and predicting the future outcome.

Regional and temporal changes in prostaglandin E2 and thromboxane B2 concentrations after spinal cord injury.

BACKGROUND CONTEXT: Inflammatory metabolites of arachidonic acid likely play a significant role in secondary injury after spinal cord trauma. PURPOSE: We sought to characterize the regional and temporal alterations in prostaglandin concentrations after injury in a rat model. STUDY DESIGN/SETTING: Prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) concentrations were measured in cerebrospinal fluid (CSF) and in different parts of the injured spinal cord at various time points after spinal cord injury. OUTCOME MEASURES: PGE2 and TxB2 levels were measured by means of an enzyme immune assay. METHODS: Forty-six adult Long Evans rats were subject to spinal cord injury using the NYU impactor. Animals were divided into three groups. Fourteen animals were used in a pilot study to determine the timing and location of PGE2 production after spinal cord injury. These animals were sacrificed, and samples of injured cord, rostral cord and CSF were assayed for PGE2 concentration. The remaining 32 animals were used to establish the time course of prostaglandin production. Twenty-eight animals were subjected to a spinal cord injury, and four animals served as sham-operated controls. These animals were sacrificed at predetermined time points 2 to 72 hours after injury, and the injured segments of spinal cord were harvested. RESULTS: Both PGE2 and TxB2 concentrations increased immediately after injury in the injured segment. PGE2 concentrations increased faster and more dramatically in the injured segment of spinal cord than in CSF or noninjured segments. Elevations in PGE2 and TxB2 concentrations were persistent for 72 hours after injury. CONCLUSION: Elevated concentrations of arachidonic acid metabolites can be detected in the injured segment of the spinal cord for at least 72 hours after injury. Concentration changes are detected earlier and are more dramatic in the injured cord segment than in rostral segments or the CSF.

Simultaneous assay of prostaglandins and thromboxane in the cerebrospinal fluid by gas chromatography-mass spectrometry-selected ion monitoring.

A method of simultaneous analysis of prostaglandins (PGs) and thromboxane (TX) B2 in cerebrospinal fluid (CSF) with GC-MS-SIM was established. Deuterated PGs and TXB2 were used as internal standards: tetra-deuterated PGE2 (d4-PGE2) for PGE2, PGE1 and PGD2; d5-PGF2alpha for PGF2alpha and 9alpha,11beta-PGF2 and 8-epi PGF2alpha; d4-TXB2 for TXB2; and d4-6-keto PGF1alpha for 6-keto PGF1alpha. The PGs and TXB2 were derivatized to the methyl ester of the methoxim dimethyisopropylsilyl (DMiPSi) ether form or the methyl ester of the DMiPSi ether form with simultaneous preparation. Samples were extracted with octadecyl silica gel and purified in two steps with silisic acid gel chromatography between derivatization steps. The calibration curve of each PG and TXB2 was linear from 10 pg to 10 ng with the isotope dilution method. The levels of the seven types of PG and of TXB2 were assayed simultaneously in the cerebrospinal fluid (CSF) from patients with aseptic meningitis. The CSF pattern of the PG and TXB2 concentrations in mumps meningitis differed from those in other types of aseptic meningitis and in disease controls.

Cerebrospinal fluid prostaglandins after systemic dipyrone intake.

OBJECTIVE: The object of this study was to evaluate the time course of thromboxane B2 and prostaglandin E2 concentrations in cerebrospinal fluid after oral administration of dipyrone (INN, metamizole). METHODS: A single 1.0 gm oral dose of dipyrone was given to consenting patients undergoing elective diagnostic lumbar puncture 0.5, 1, 1.5, 2, 4, 6, 8, or 12 hours before the tap. RESULTS: For thromboxane B2 a time decrease in cerebrospinal fluid concentration was apparent. In contrast, for prostaglandin E2 cerebrospinal fluid levels no consistent trend was observed. CONCLUSIONS: A time-related decrease in cerebrospinal fluid thromboxane B2 level was noted in patients receiving dipyrone. Thirty minutes after dipyrone intake cerebrospinal fluid thromboxane B2 levels already tended to be lower than those seen in patients with neurologic diseases who were not receiving dipyrone. These results are consistent with the hypothesis that dipyrone acts in the central nervous system by inhibition of particular prostanoids.

Effect of ciliary neurotrophic factor on body temperature and cerebrospinal fluid prostanoids in the cat.

It has been proposed that ciliary neurotrophic factor (CNTF) belongs to the group of cytokines causing fever in response to infectious and inflammatory noxae. The present investigation was undertaken in the conscious cat to verify whether CNTF (human type, hCNTF) is pyrogenic when given either intravenously (i.v.) or intracerebroventricularly (i.c.v.) and correlate at the same time body temperature with cerebrospinal fluid (CSF) levels of prostaglandin (PG) E2 (i.e., the putative fever mediator in brain) and thromboxane (TX) B2 (the stable TXA2 byproduct) in untreated vs. treated animals. hCNTF (10 microg/kg i.v.; 1 microg i.c.v.) caused fever by both routes and the increase in body temperature was associated with an upward change in CSF PGE2. Conversely, CSF TXB2 showed no elevation. Similarly unaffected was CSF TXB2 by human interleukin 6 (hIL-6, 1 microg i.c.v.), a cytokine with known pyrogenic and PGE2-promoting actions sharing the signal-transducing mechanism with hCNTF. We conclude that CNTF lends itself to a role in the pathogenesis of fever. The modest PGE2 elevation relatively to other cytokines, specifically hIL-1, is ascribed to the fact that CNTF activates the inducible isoform of arachidonate cyclooxygenase, which is constitutively expressed in brain, without concomitantly promoting the formation of new enzyme.

Experimental and clinical studies of eicosanoids in cerebrospinal fluid after spinal cord injury.

OBJECTIVE: In an attempt to elucidate a possible role for eicosanoids in the pathogenesis of spinal cord injury (SCI), we measured the concentration of leukotriene (LT) C4, thromboxane B2, and 6-keto-prostaglandin F1 alpha in cerebrospinal fluid in both a canine experimental model and 11 patients with SCIs. METHODS: The eicosanoid concentration in cerebrospinal fluid was measured by radioimmunoassay. Neurological severity was assessed according to the grading system of Frankel et al.. Control samples were obtained from 20 patients without SCIs. RESULTS: In the canine model, a significant increase in all eicosanoid levels was found on Days 1 to 7, which subsequently returned to the control levels. In the clinical study, the highest mean (+/- standard error of the mean) concentrations of LTC4, thromboxane B2, and 6-keto-prostaglandin F1 alpha in the acute stage of SCI were 95.9 +/- 10.7, 175.2 +/- 38.2, and 167.5 +/- 39.9 pg/ml, respectively. These concentrations were five to nine times higher than control levels. There was a good correlation between cerebrospinal fluid LTC4 levels and the neurological severity. The time-dependent change in LTC4 concentrations in seven patients with SCIs was similar to that observed in the canine model. In addition, the highest mean concentrations of the eicosanoids measured in patients with complete paralysis was also similar to those of the canine model. The eicosanoid concentrations in five patients with SCI were measured more than 6 months after the onset of injury. Although all eicosanoid levels had elevated in the acute stage of injury, they were not elevated and showed the same levels as the controls at the chronic stage. CONCLUSION: The findings suggest that enhanced arachidonate metabolism occurs in humans and support the evidence from animal experiments that emphasizes the importance of eicosanoids in the secondary processes mediating ischemia and edema.

Effect of intraventricular haemorrhage and rebleeding following subarachnoid haemorrhage on CSF eicosanoids.

CSF eicosanoid levels are raised following subarachnoid haemorrhage but not sufficiently to be vasoactive per se within the cerebral circulation. Rebleeding and intraventricular haemorrhage are two factors associated with a worse outcome after aneurysmal SAH. We have examined the effects of these two factors on the CSF levels of TXB2 (TXA2 metabolite), PG6-keto F1 alpha (prostacyclin metabolite), PGF2 alpha and PGE2 in 44 patients following subarachnoid haemorrhage. In 15 patients who had received no non-steroidal anti-inflammatory agent or dexamethasone, intraventricular haemorrhage increased the median levels of all four eicosanoids in ventricular CSF by 2.1-5.1-fold. In 4 patients who rebled, the CSF median levels of all four eicosanoids were raised up to 250-fold over the normal range. These concentrations are just sufficient to have cerebrovascular and neuromodulatory effects.

Eicosanoids in third ventricular cerebrospinal fluid of fetal and newborn sheep.

A method to serially sample cerebrospinal fluid (CSF) from the third ventricle of chronically catheterized fetal and newborn sheep was developed. Either sampling cannulas of preset lengths ("fixed-probe" technique) or a single cannula that could be positioned at the desired depth ("roving-probe" technique) was used. The roving probe proved superior because free CSF flow was obtained in seven of ten animals after surgery compared with two of nine animals implanted with a fixed probe. CSF (5 animals) and plasma (7 animals) was collected serially from 2 wk before to 2 wk after birth, including the time around labor. Prostaglandin E2 (PGE2) levels (means +/- SE) were significantly higher in CSF (366 +/- 120 pg/ml; n = 5) and plasma (520 +/- 69 pg/ml; n = 7) before the day of delivery than in the same animals after birth. During labor, CSF and plasma PGE2 levels increased significantly to 1,428 +/- 643 pg/ml in CSF and to 2,015 +/- 414 pg/ml in plasma. However, by 1 h after birth, PGE2 had fallen to 366 +/- 165 pg/ml in CSF and to 338 +/- 106 pg/ml in plasma; levels similar to those observed in the fetus before labor. PGE2 continued to decrease precipitously and, at 24 h of age, levels were significantly less than those observed in the fetus. PGE2 levels were near the limit of detection of the assay in CSF (< 5 pg/ml) and were 49 +/- 10 pg/ml in plasma. In contrast, CSF thromboxane B2 (n = 2) and total peptidoleukotriene content (n = 4) showed little change during labor or after birth.(ABSTRACT TRUNCATED AT 250 WORDS)

Release of proinflammatory and prothrombotic mediators in the brain and peripheral circulation in spontaneously hypertensive and normotensive Wistar-Kyoto rats.

BACKGROUND AND PURPOSE: We reported previously that stroke risk factors prepared the brain stem for the development of ischemia and hemorrhage and induced the production of tumor necrosis factor following an intrathecal injection of lipopolysaccharide, a prototypic monocyte-activating stimulus. This study evaluates whether blood or brain cells of hypertensive rats produce more proinflammatory and prothrombotic mediators than do blood or brain cells of normotensive rats. METHODS: Levels of tumor necrosis factor, platelet-activating factor, 6-ketoprostaglandin F1 alpha, and thromboxane B2 in the cerebrospinal fluid and blood of spontaneously hypertensive and normotensive Wistar-Kyoto rats were monitored before and after a challenge with lipopolysaccharide. RESULTS: Little or no activity from these mediators was found in the cerebrospinal fluid or blood of saline-injected control animals. Intravenous administration of lipopolysaccharide (0.001, 0.1, and 1.8 mg/kg) produced dose-dependent increases in blood levels of all mediators in hypertensive rats. In normotensive rats the levels were less than in hypertensive rats and were not clearly dose-related. When lipopolysaccharide was injected intracerebroventricularly, more tumor necrosis factor was measured in the cerebrospinal fluid than in the blood, suggesting local synthesis of this cytokine. Levels of tumor necrosis factor and platelet-activating factor in the cerebrospinal fluid were higher in hypertensive than in normotensive rats. The thromboxane A2/prostacyclin ratio was not altered significantly between the two rat strains. CONCLUSIONS: It is suggested that the higher incidence of brain stem ischemia and hemorrhage after the intrathecal injection of lipopolysaccharide in hypertensive rats than in normotensive rats might be related to the higher levels of the two cytotoxic factors tumor necrosis factor and platelet-activating factor produced in response to such challenge.

Effect of dexamethasone on cerebral prostanoid formation and pial arteriolar reactivity to CO2 in newborn pigs.

This study investigates the effect of glucocorticoid treatment on the relationship between arteriolar PCO2 and cortical prostanoid production and on cerebrovascular responsiveness to elevated CO2 in newborn piglets. The response of pial arteries to hypercapnia (fractional inspired CO2 = 0.035 and 0.07) was studied in 18 anesthetized newborn piglets, 9 of which were pretreated with dexamethasone (2 mg.kg-1.day-1 for 36-48 h). Pial arterioles (77-122 microns diam) were monitored using a closed cranial window and intravital microscopy. Perivascular cerebrospinal fluid (CSF) was sampled from the cortical surface and analyzed for 6-keto-prostaglandin F1 alpha and thromboxane B2 (TxB2) using radioimmunoassay. In the dexamethasone-treated animals the increase in arteriolar diameter to CO2 was diminished by approximately 50% for each respective CO2 concentration vs. the control group. Acute sympathetic denervation did not restore the CO2 dilator response. Dexamethasone did not alter baseline cortical CSF prostanoid concentrations but abolished the CO2-induced increase in CSF prostanoids. The dilator response to exogenously applied prostaglandin E2 was inhibited in dexamethasone-treated animals. However, the dilator response to exogenous adenosine and the contractile response to prostaglandin F2 alpha were not altered in the dexamethasone-treated piglets. The data support the concept that metabolites of arachidonic acid participate in the cerebrovascular response to CO2 and suggest that glucocorticoid treatment may influence cerebrovascular tone via this mechanism.

Effect of hydrocephalus on prostaglandins and thromboxane B2 in ventricular cerebrospinal fluid.

The concentrations of prostaglandin F2 alpha, prostaglandin E2, 6-ketoprostaglandin F1 alpha (prostacyclin metabolite), and thromboxane B2 were assayed in ventricular cerebrospinal fluid obtained from 28 patients with hydrocephalus (17 obstructive, 11 communicating). Seven patients received dexamethasone or hydrocortisone on the day of sampling. No patient received nonsteroidal anti-inflammatory compounds for 48 hours before sampling. The median values did not differ significantly between the two types of hydrocephalus or from the concentrations in lumbar cerebrospinal fluid obtained from patients without intracranial pathology during lumbar myelography for possible lumbar disc disease. Hence, there is no evidence that eicosanoids accumulate in the ventricles in hydrocephalus, and it is unlikely that they have a significant role in its symptomatology.

Metabolism of central neurotransmitters during development of tolerance to the anticonvulsant effect of clonazepam and of physical dependence on the drug in dogs.

In previous studies, development of functional tolerance to the anticonvulsant effect of clonazepam and physical dependence on the drug have been demonstrated. In the present study, dogs were treated for 6 weeks with clonazepam 0.5 mg/kg b.i.d. Under methohexital anesthesia, cerebrospinal fluid samples were taken before treatment, at 3 days (acute effect), 4 and 5 weeks (tolerance) after the start of treatment, 2 and 8 days after withdrawal and 5 weeks after the end of treatment as another control. The following transmitters or metabolites were determined: HVA, VMA, 5-HIAA, GABA, PGE2, TXB2 and 6-keto PGF1 alpha. 5-HIAA levels showed a significant rise, indicating an increased activity of the serotonergic system in the brain during development both of tolerance and withdrawal. Dopaminergic activity was not altered during treatment, but was increased after cessation of treatment, as indicated by a significant increase in HVA concentrations.

Eicosanoid levels in CSF of premature infants with posthemorrhagic hydrocephalus.

The cerebrospinal fluid (CSF) of 11 premature infants suffering from posthemorrhagic hydrocephalus was examined by radioimmunoassay for prostaglandin (PG) E2, PGF2 alpha, PGD2, 6-keto PGF1 alpha, thromboxane B2 (TxB2) and peptidoleukotrienes (LTC4/LTD4). The LTs were detected in the CSF of more of these patients (70%) than any of the other eicosanoids, and usually in the highest concentration. Among the 11 posthemorrhagic patients CSF eicosanoid levels were highest when determined soon after injury. Moreover, the variety of eicosanoids present, as well as concentrations, in these infants decreased with time. The types of eicosanoids most evident in the CSF of patients who required shunting were TxB2 and LTs, being present together in 5 of 6 (83%) of these infants. In contrast, 1 of 5 (20%) of the patients who did not require this neurosurgical intervention contained both TxB2 and LTs, the remaining having only one or neither eicosanoid. The highest average concentration for each eicosanoid studied was (pg/ml): PGE2, 628; PGF2 alpha, 985; PGD2, 1410; 6-keto PGF1 alpha, 544; TxB2, 486 and LTs, 1229. This study is the first to demonstrate that the CSF of preterm infants may contain a wide variety of eicosanoids and indicates that these lipids are a manifestation of neurological assault.

Effect of experimental subarachnoid hemorrhage on CSF eicosanoids in the rat.

A simple and inexpensive experimental model of subarachnoid hemorrhage (SAH) was developed in the rat. Based on accumulating data indicating the important role of arachidonic acid metabolites in the etiology of delayed cerebral vasospasm, we investigated changes induced by SAH on cerebrospinal fluid (CSF) levels of prostaglandin E2 (PGE2), F2 alpha (PGF2 alpha), and thromboxane B2 (TXB2). SAH was produced by the cisternal injection of blood via percutaneous suboccipital puncture. SAH rats (n = 200) were injected with 300 microliters of fresh autologous arterial blood; Control rats (n = 100) received the same volume of mock CSF. In 60 additional animals, no injections were made. To follow the changes induced by SAH on both the spectrum and time course of CSF eicosanoids, cisternal CSF samples were collected under basal conditions, 6, 12, and 36 after cisternal injection. PGE2, PGF2 alpha, and TXB2 were assayed in aliquots of CSF obtained by pooling samples from each experimental group. Eicosanoids were assayed using radioimmunoassay techniques. Arterial spasm was verified in parallel groups of SAH and control rats by comparison of the angiographic diameters of the basilar arteries (BA) and middle cerebral arteries (MCA) to that of the stapedial artery. CSF levels of all three eicosanoids were significantly higher in the SAH groups compared to both noninjected and mock-CSF injected control rats. These increases in concentrations of eicosanoids were accompanied by a decrease in the mean vascular diameter (77.5-82.0% of control) on day 2 following cisternal injection. We conclude that marked elevations of spasmogenic eicosanoids in the CSF are associated with experimental SAH.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of chronic cerebral vasospasm in dogs with ibuprofen and high-dose methylprednisolone.

Severe chronic cerebral vasospasm was produced in dog basilar arteries by two injections, 2 days apart, of autologous blood into the cisterna magna of 25 dogs. Treatment with ibuprofen (n = 8) or high-dose methylprednisolone (n = 8) after the first injection of blood prevented or reduced angiographic vasospasm. Cerebrospinal fluid concentrations of prostaglandin E2, prostaglandin F2 alpha, 6-ketoprostaglandin F1 alpha (a metabolite of prostacyclin), and thromboxane B2 (a metabolite of thromboxane A2) were measured in both treated and untreated (n = 7) dogs. In untreated dogs, the level of prostaglandin E2 increased 94-fold by Day 8 after the first injection of blood and was strongly and positively correlated with the degree of angiographic vasospasm. Treatment with ibuprofen and high-dose methylprednisolone prevented or significantly reduced this increase in prostaglandin E2 concentration. Smaller increases in cerebrospinal fluid concentrations of thromboxane B2 and 6-ketoprostaglandin F1 alpha occurred after experimental subarachnoid hemorrhage; the magnitude of these increases was also reduced by ibuprofen or high-dose methylprednisolone treatment. In contrast, prostaglandin F2 alpha levels were not significantly altered during the study. These data show that enhanced prostaglandin E2 synthesis occurs during experimental subarachnoid hemorrhage, and the by-products generated in its synthesis may play a role in the pathogenesis of cerebral vasospasm.

Lumbar CSF eicosanoids in neonates.

Lumbar CSF eicosanoids were measured in 11 neonates with perinatal asphyxia and 12 neonates with suspected sepsis. In the asphyxia group low levels of thromboxane B2 and prostaglandin F2a were detected in five neonates, all of which had had a lumbar puncture prior to 4 hours of age. In the group with suspected sepsis two infants had positive blood cultures and one had strep meningitis. CSF eicosanoids were nondetectable in all patients in this second group with the exception of the infant with meningitis. With meningitis CSF eicosanoids were markedly elevated. These findings suggest that lumbar CSF eicosanoids do not appear to be a clinically useful tool. The data further suggest that eicosanoids are involved in the inflammatory response to meningitis.

Complement-derived polypeptide C3adesArg as a mediator of inflammation at the blood-brain barrier in a new experimental cat model.

The effect of the complement-derived polypeptide C3adesArg as a mediator of inflammation in the central nervous system was examined. Twenty-five anesthetized cats received 4 mg of this polypeptide by intraventricular injection, 20 cats who served as controls received saline. Cerebrospinal fluid (CSF) was sampled 3 h after intraventricular injection and the brains were removed. For assessment of the permeability of the blood-brain barrier the CSF penetration of four antibiotics, which were given intravenously was measured. Five control animals were employed for each antibiotic (tobramycin, ampicillin, imipenem, fosfomycin), whereas six C3adesArg-treated animals were used for each antibiotic and seven for tobramycin. Besides CSF levels of glucose, the prostanoids 6-keto-prostaglandin F1 alpha, thromboxane B2 and prostaglandin E2 were measured. The morphological examinations in the CSF sediments and histological brain sections in the C3adesArg-treated animals disclosed a distinct inflammation with leptomeningeal and perivascular infiltration of polymorphonuclear granulocytes compared to normal findings in the controls. The CSF/serum ratios of all of the antibiotics were markedly elevated compared to controls, indicating a blood-brain barrier disruption. The levels of all prostanoids were significantly higher in the treatment group than in the control group, whereas the glucose levels were lower. These findings are in accordance with a granulocytic meningitis as seen in some infections at the acute stage. It is concluded that C3adesArg acts as a mediator of inflammation in the central nervous system.