Effects of tacrolimus on hemispheric water content and cerebrospinal fluid levels of glutamate, hypoxanthine, interleukin-6, and tumor necrosis factor-α following controlled cortical impact injury in rats

2001 ◽  
Vol 94 (5) ◽  
pp. 782-787 ◽  
Author(s):  
John F. Stover ◽  
Britta Schöning ◽  
Oliver W. Sakowitz ◽  
Christian Woiciechowsky ◽  
Andreas W. Unterberg
Keyword(s):  
Cerebrospinal Fluid ◽  
Tissue Damage ◽  
Tumor Necrosis ◽  
Edema Formation ◽  
Content Type ◽  
Controlled Cortical Impact Injury ◽  
Csf Levels ◽  
Impact Injury ◽  
Necrosis Factor ◽  
Fine Print

Object. Disturbance of calcium homeostasis contributes to evolving tissue damage and energetic impairment following traumatic brain injury (TBI). Calcium-mediated activation of calcineurin results in production of tissue-damaging nitric oxide and free oxygen radicals. Inhibition of calcineurin induced by the immunosuppressant tacrolimus (FK506) has been shown to reduce structural and functional damage after ischemia. The aims of the present study were to investigate time- and dose-dependent short-term antiedematous effects of tacrolimus following TBI. Methods. A left temporoparietal contusion (controlled cortical impact injury [CCII]) was induced in 51 male Sprague—Dawley rats. Tacrolimus (1 or 3 mg/kg body weight) was administered by a single intraperitoneal injection at 5 minutes, 30 minutes, or 4 hours after CCII occurred. Control rats received physiological saline. Water contents of traumatized and nontraumatized hemispheres, as well as cerebrospinal fluid (CSF) levels of mediators reflecting tissue damage (the proinflammatory cytokines interleukin [IL]-6 and tumor necrosis factor [TNF]—α, the excitotoxin glutamate, and the adenosine triphosphate—degradation product hypoxanthine), were determined 24 hours after trauma. Although CSF levels of IL-6 and TNFα were completely suppressed by tacrolimus at all time points and at both concentrations, CSF levels of glutamate and hypoxanthine, as well as edema formation, were only marginally influenced. Significant reduction of cerebral water content was confined to nontraumatized hemispheres. In addition, the higher dose of tacrolimus failed to exert significant antiedematous effects on traumatized hemispheres. Conclusions. Under the present study design, the potency of tacrolimus in reducing edema formation following CCII seems limited. However, its immunosuppressive effects could be of value in influencing the posttraumatic inflammatory response known to aggravate tissue damage.

Significant reduction in brain swelling by administration of nonpeptide kinin B2 receptor antagonist LF 16—0687Ms after controlled cortical impact injury in rats

2000 ◽  
Vol 92 (5) ◽  
pp. 853-859 ◽  
Author(s):  
John F. Stover ◽  
Nils-Kristian Dohse ◽  
Andreas W. Unterberg
Keyword(s):  
Receptor Antagonist ◽  
Water Content ◽  
Brain Edema ◽  
Single Administration ◽  
Brain Swelling ◽  
Edema Formation ◽  
Content Type ◽  
Controlled Cortical Impact Injury ◽  
Impact Injury ◽  
Fine Print

Object. Identification of new therapeutic agents aimed at attenuating posttraumatic brain edema formation remains an unresolved challenge. Among others, activation of bradykinin B2 receptors is known to mediate the formation of brain edema. The purpose of this study was to investigate the protective effect of the novel nonpeptide B2 receptor antagonist, LF 16-0687Ms, in brain-injured rats.Methods. Focal contusion was produced by controlled cortical impact injury. Five minutes after trauma, the rats received a single dose of no, low- (3 mg/kg body weight), or high- (30 mg/kg) dose LF 16-0687Ms. After 24 hours, the amount of brain swelling and hemispheric water content were determined. Low and high doses of LF 16-0687Ms significantly reduced brain swelling by 25% and 27%, respectively (p < 0.03). Hemispheric water content tended to be increased in the nontraumatized hemisphere.In a subsequent series of 10 rats, cisternal cerebrospinal fluid (CSF) samples were collected to determine whether changes in substances associated with edema formation could clarify why LF 16-0687Ms increases water content. For this, the volume regulator amino acid taurine, the excitatory transmitter glutamate, and the adenosine triphosphate degradation products hypoxanthine and xanthine were measured. In CSF, the levels of taurine, hypoxanthine, and xanthine were significantly decreased following a single administration of LF 16-0687Ms (p < 0.005); the level of glutamate, however, was double that found in control animals (p < 0.05).Conclusions. Using the present study design, a single administration of LF 16-0687Ms successfully reduced posttraumatic brain swelling. The decreased levels of taurine, hypoxanthine, and xanthine may reflect reduced posttraumatic brain edema, whereas the increased level of glutamate could account for the elevated water content observed in the nontraumatized hemisphere.

A morphological and ultrastructural investigation of normal mouse brain tissue after intracerebral injection of tumor necrosis factor

1992 ◽  
Vol 77 (2) ◽  
pp. 279-287 ◽  
Author(s):  
Toshiki Yamasaki ◽  
Haruhiko Kikuchi ◽  
Kouzo Moritake ◽  
Seiichi Nagao ◽  
Kouichi Iwasaki ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Brain Tissue ◽  
Mouse Brain ◽  
Tumor Necrosis ◽  
Normal Mouse ◽  
Mononuclear Cell Infiltration ◽  
Content Type ◽  
Normal Mouse Brain ◽  
Necrosis Factor ◽  
Fine Print

✓ Morphological and ultrastructural changes in normal mouse brain tissue were investigated after intracerebral stereotactic injections of tumor necrosis factor (specific activity: 2.0 × 106 U/mg protein) into the right frontal lobe. The mice received either a single infusion or multiple tumor necrosis factor infusions in three different dose groups (10, 100, or 500 U). Compared with sham-treated control mice that received adjusted intracerebral injections of purified albumin, the tumor necrosis factor-treated mice in all dose groups did not show any specific in vivo behavioral abnormalities during the 2 months of study following the infusions. Histological studies revealed hemorrhage attributable to the mechanics of the intracerebral infusions, a thickening of the arachnoid membranes, a reactive gliosis, and neutrophilic and/or mononuclear cell infiltration along the infusion pathway. A local neutrophilic response was prominent 1 day after tumor necrosis factor injection. An immunohistochemical analysis indicated that the mononuclear cell infiltration consisted of lymphocytes and macrophages. Except for the transient neutrophilic infiltration, these histological alterations did not differ from those seen in the sham-treated control groups, and most nonspecific reactive changes disappeared within 8 weeks after the injections. Furthermore, an ultrastructural study showed no apparent pathological changes in the cytoplasmic organelles of neuronal, glial, and endothelial cells in the tumor necrosis factor-injected mouse specimens. These results suggest that the tumor necrosis factor injections caused no specific toxicity and did not alter the parenchymal and stromal cells comprising normal mouse brain tissue.

Long-term results of praziquantel therapy in neurocysticercosis

1987 ◽  
Vol 66 (3) ◽  
pp. 359-363 ◽  
Author(s):  
Clemente Robles ◽  
Ana Maria Sedano ◽  
Noe Vargas-Tentori ◽  
Sonia Galindo-Virgen
Keyword(s):  
Cerebrospinal Fluid ◽  
Intracranial Hypertension ◽  
Tissue Damage ◽  
Long Term Results ◽  
Content Type ◽  
Low Concentration ◽  
Praziquantel Treatment ◽  
Fine Print

✓ The long-term results of praziquantel therapy in 141 patients with neurocysticercosis are presented. Seventy-five patients (53%) were considered to be cured because the cysts or nodules disappeared or became calcified following praziquantel treatment and the patients were asymptomatic at the end of a 5-year follow-up period. An additional 35 patients (24.8%) improved clinically and radiographically. The intraventricular Cysticercus cysts of five patients in this group were not affected by praziquantel and had to be surgically removed. The remaining 31 patients (21.9%) were unchanged or became worse probably because, prior to therapy, Cysticercus larvae had caused tissue damage. The fact that praziquantel did not affect intraventricular cysts suggests a low concentration of the drug in the cerebrospinal fluid. Surgery continues to be an important tool in the treatment of cysticercosis to remove parasites that do not respond to praziquantel therapy as well as for the relief of intracranial hypertension.

Cerebrospinal fluid interleukin-1 receptor antagonist and tumor necrosis factor—α following subarachnoid hemorrhage

1997 ◽  
Vol 87 (2) ◽  
pp. 215-220 ◽  
Author(s):  
Tiit Mathiesen ◽  
Göran Edner ◽  
Elfar Ulfarsson ◽  
Birger Andersson
Keyword(s):  
Brain Damage ◽  
Clinical Condition ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Nitric Oxide Synthesis ◽  
Content Type ◽  
Cytokine Levels ◽  
Factor Α ◽  
Necrosis Factor ◽  
Fine Print

✓ Subarachnoid hemorrhage (SAH) causes an inflammatory reaction and may lead to ischemic brain damage. Experimental ischemia has been shown to be connected with the alarm-reaction cytokines interleukin-1 receptor antagonist (IL-1Ra) and tumor necrosis factor—α (TNFα). Increased levels of these cytokines, however, have not been detected thus far in patients following an SAH event. For this reason daily cerebrospinal fluid (CSF) samples were collected from 22 consecutively enrolled patients with SAH and from 10 non-SAH patients (controls). The CSF samples were studied using immunoassays for IL-1Ra and TNFα to investigate whether an SAH caused increased cytokine levels. The mean IL-1Ra levels were significantly higher in patients with SAH who were in poor clinical condition on admission than in those who were in good condition (318 pg/ml vs. 82 pg/ml, p < 0.02). The IL-1Ra levels increased during delayed ischemic episodes and after surgery in patients who were in poor clinical condition. Significant increases in IL-1Ra and TNFα were detected during Days 4 through 10 in patients suffering from SAH who eventually had a poor outcome (p < 0.05). Patients with good outcomes and control patients had low levels of these cytokines. The levels of IL-1Ra increased after surgery in patients with Hunt and Hess Grades III through V, but not in those with Grade I or II. This finding indicates that patients in poor clinical condition have a labile biochemical state in the brain that is reflected in increased cytokine levels following the surgical trauma. Both IL-1Ra and TNFα are known to induce fever, malaise, leukocytosis, and nitric oxide synthesis and to mediate ischemic and traumatic brain injuries. The present study shows that levels of these cytokines increase after SAH occurs and that high cytokine levels correlate with brain damage. It is therefore likely that fever, leukocytosis, and nitric oxide synthesis are also mediated by IL-1 in patients suffering from SAH and it is probable that the inflammatory mediators contribute to brain damage.

Effect of cerebral perfusion pressure on contusion volume following impact injury

1999 ◽  
Vol 90 (3) ◽  
pp. 520-526 ◽  
Author(s):  
Stefan-Nikolaus Kroppenstedt ◽  
Michael Kern ◽  
Ulrich-Wilhelm Thomale ◽  
Gerd-Helge Schneider ◽  
Wolfgang Reinhardt Lanksch ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cerebral Perfusion Pressure ◽  
Cerebral Perfusion ◽  
Perfusion Pressure ◽  
Experimental Conditions ◽  
Content Type ◽  
Arterial Blood ◽  
Controlled Cortical Impact Injury ◽  
Impact Injury ◽  
Fine Print

Object. Although it is generally acknowledged that a sufficient cerebral perfusion pressure (CPP) is necessary for treatment of severe head injury, the optimum CPP is still a subject of debate. The purpose of this study was to investigate the effect of various levels of blood pressure and, thereby, CPP on posttraumatic contusion volume.Methods. The left hemispheres of 60 rats were subjected to controlled cortical impact injury (CCII). In one group of animals the mean arterial blood pressure (MABP) was lowered for 30 minutes to 80, 70, 60, 50, or 40 mm Hg 4 hours after contusion by using hypobaric hypotension. In another group of animals the MABP was elevated for 3 hours to 120 or 140 mm Hg 4 hours after contusion by administering dopamine. The MABP was not changed in respective control groups. Intracranial pressure (ICP) was monitored with an ICP microsensor. The rats were killed 28 hours after trauma occurred and contusion volume was assessed using hematoxylin and eosin—stained coronal slices. No significant change in contusion volume was caused by a decrease in MABP from 94 to 80 mm Hg (ICP 12 ± 1 mm Hg), but a reduction of MABP to 70 mm Hg (ICP 9 ± 1 mm Hg) significantly increased the contusion volume (p < 0.05). A further reduction of MABP led to an even more enlarged contusion volume. Although an elevation of MABP to 120 mm Hg (ICP 16 ± 2 mm Hg) did not significantly affect contusion volume, there was a significant increase in the contusion volume at 140 mm Hg MABP (p < 0.05; ICP 18 ± 1 mm Hg).Conclusions. Under these experimental conditions, CPP should be kept within 70 to 105 mm Hg to minimize posttraumatic contusion volume. A CPP of 60 mm Hg and lower as well as a CPP of 120 mm Hg and higher should be considered detrimental.

scholarly journals Tumor necrosis factor-alpha, interleukin-1beta and interleukin-6 in the cerebrospinal fluid of newborn with meningitis

2005 ◽  
Vol 63 (1) ◽  
pp. 7-13 ◽  
Author(s):  
Vera Lúcia Jornada Krebs ◽  
Thelma Suely Okay ◽  
Yassuhiko Okay ◽  
Flávio Adolfo Costa Vaz
Keyword(s):  
Cerebrospinal Fluid ◽  
Tumor Necrosis Factor ◽  
Early Diagnosis ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Csf Levels ◽  
Factor Alpha ◽  
Necrosis Factor

OBJECTIVE: To analyze the usefulness of determining the cerebrospinal fluid(CSF) levels of tumor necrosis factor-alpha(TNF-alpha),interleukin-1beta(IL-1beta) and interleukin-6(IL-6)for the early diagnosis and evaluation of the prognosis of neonatal meningitis. METHOD: We studied 54 newborn that underwent lumbar puncture.Thirty patients had meningitis and 24 were the control group.CSF and sera were obtained at the moment of suspicion of meningitis and stored at -70(0)C.Cytokines were performed by enzyme-linked immunosorbent assay method. RESULTS: CSF cytokines were detected in all the newborn with meningitis.TNF-alpha was detected in the CSF in 63.3% of the neonates, IL-1beta in 73.3% and IL-6 in 96.6%.The CSF levels were significantly higher than serum in neonates with meningitis.There was no correlation between the CSF levels of cytokines and neurologic complications. CONCLUSION: The detection of TNF-alpha, IL-1beta and IL-6 in the CSF is of great value in order to achieve a early diagnosis of neonatal meningitis.Among the three cytokines analyzed, IL-6 was the best indicator of meningeal inflammation.

Adult hydrocephalus

1972 ◽  
Vol 37 (4) ◽  
pp. 423-428 ◽  
Author(s):  
James H. Salmon
Keyword(s):  
Cerebrospinal Fluid ◽  
Infection Rate ◽  
Tissue Damage ◽  
Cerebral Atrophy ◽  
Shunt Operation ◽  
Content Type ◽  
Case Selection ◽  
Selection History ◽  
Basal Cisterns ◽  
Fine Print

✓ Eighty adults with hydrocephalus were treated with a shunt operation. Twenty-four had nonabsorptive hydrocephalus with obstruction at the level of the basal cisterns and 56 had hydrocephalus plus cerebral atrophy without apparent obstruction to the flow of cerebrospinal fluid. Thirty-four patients improved but in only 16 (20%) was the improvement dramatic. The material was analyzed to identify criteria for future case selection. History, evidence of tissue damage, and thickness of cerebral mantle were considered important. Antibiotics reduced infection rate from 19% to 3%.

Recurrent intracranial solitary fibrous tumor with cerebrospinal fluid dissemination

2004 ◽  
Vol 101 (6) ◽  
pp. 1045-1048 ◽  
Author(s):  
Katsuyoshi Miyashita ◽  
Yutaka Hayashi ◽  
Hironori Fujisawa ◽  
Mitsuhiro Hasegawa ◽  
Junkoh Yamashita
Keyword(s):  
Cerebrospinal Fluid ◽  
Malignant Transformation ◽  
Solitary Fibrous Tumor ◽  
S100 Protein ◽  
Spinal Tumors ◽  
Content Type ◽  
Csf Dissemination ◽  
Fibrous Tumor ◽  
Fine Print ◽  
Mib 1

✓ Solitary fibrous tumor (SFT) is a benign and rare neoplasm. To date, only 37 patients with intracranial SFTs have been reported. Although a number of the tumors were recurrent and some later underwent malignant transformation, none of these lesions progressed to cerebrospinal fluid (CSF) dissemination. In this paper the authors report a case of SFT in which the lesion recurred several times and ultimately was disseminated by the CSF. The patient was a 63-year-old woman with multiple intracranial and spinal tumors. Fifteen years before this presentation, at the age of 48 she had been hospitalized for resection of a falcotentorial tumor. During the ensuing 15 years she underwent multiple surgeries and sessions of radiation therapy for recurrent lesions. The exclusive location of her tumors in the subarachnoid space at the end of this 15-year period indicate CSF dissemination of the tumor. The tumor that was resected when the patient was 48 years old and the latest resected lesion were analyzed by performing immunohistological CD34, epithelial membrane antigen, vimentin, S100 protein, and reticulin staining, and determining the MIB-1 labeling index (LI). Most of the results were identical, and both tumors were diagnosed as SFT according to a staining pattern that showed a strong and diffuse positive reaction for CD34. Nevertheless, the authors noted that the MIB-1 LI increased from less than 1% in the original tumor to 13% in the latest tumor. The increased proliferation of MIB-1 indicates that the malignant transformation could have occurred during tumor recurrence with CSF dissemination.

Evaluation of endorphin content in the CSF of patients with trigeminal neuralgia before and after Gasserian ganglion thermocoagulation

1981 ◽  
Vol 55 (6) ◽  
pp. 935-937 ◽  
Author(s):  
Giuseppe Salar ◽  
Salvatore Mingrino ◽  
Marco Trabucchi ◽  
Angelo Bosio ◽  
Carlo Semenza
Keyword(s):  
Cerebrospinal Fluid ◽  
Trigeminal Neuralgia ◽  
Control Group ◽  
Gasserian Ganglion ◽  
Content Type ◽  
Group Of Seven ◽  
Idiopathic Trigeminal Neuralgia ◽  
Significant Difference ◽  
Before And After ◽  
Fine Print

✓ The β-endorphin content in cerebrospinal fluid (CSF) was evaluated in 10 patients with idiopathic trigeminal neuralgia during medical treatment (with or without carbamazepine) and after selective thermocoagulation of the Gasserian ganglion. These values were compared with those obtained in a control group of seven patients without pain problems. No statistically significant difference was found between patients suffering from trigeminal neuralgia and those without pain. Furthermore, neither pharmacological treatment nor surgery changed CSF endorphin values. It is concluded that there is no pathogenetic relationship between trigeminal neuralgia and endorphins.

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