Blood-brain barrier permeability in staphylococcal cerebritis and early brain abscess

1994 ◽  
Vol 80 (5) ◽  
pp. 897-905 ◽  
Author(s):  
Warren D. Lo ◽  
Arlene Wolny ◽  
Carl Boesel
Keyword(s):  
Blood Flow ◽  
Brain Edema ◽  
Brain Abscess ◽  
Blood Brain Barrier ◽  
Plasma Volume ◽  
Brain Barrier ◽  
Content Type ◽  
Blood Brain ◽  
Bbb Permeability ◽  
Fine Print

✓ The pattern of radiographic enhancement in cases of brain abscess has been extensively studied, but the magnitude of blood-brain barrier (BBB) damage that accompanies enhancement has not. The question of whether BBB permeability increases continuously as a cerebritis evolves into an abscess was studied. The tracers 3H-labeled aminoisobutyric acid and 14C-labeled butanol were used in a rat Staphylococcus aureus cerebritis model to measure simultaneously BBB permeability and blood flow. The rats were examined at 1, 2, 3, 5, or 7 days after inoculation, and tissue samples were collected from the cerebritis site and uninoculated regions. Permeability of the BBB in the cerebritis region increased to five times the normal values by 72 hours after inoculation, then reached a plateau. The plasma volume in the cerebritis region increased to six times greater than the normal value at 72 hours, then remained unchanged. Uninoculated brain in both ipsilateral and contralateral hemispheres showed no significant changes. Cerebral blood flow was not substantially altered at the inoculated or uninoculated sites. In this model, incidence of BBB damage rises rapidly, reaches a plateau, and does not continue to increase despite the ongoing evolution of a cerebritis into an abscess. The BBB damage is accompanied by an increase in the regional plasma volume, a novel finding that has not been previously reported in central nervous system inflammation. These results suggest that the vascular events contributing to brain edema formation become established early in the cerebritis phase and imply that control of the host's inflammatory response is important in the management of cerebritis-associated brain edema.

Neuroprotective effects of citicoline on brain edema and blood—brain barrier breakdown after traumatic brain injury

2000 ◽  
Vol 92 (3) ◽  
pp. 448-452 ◽  
Author(s):  
Mustafa K. Başkaya ◽  
Aclan Doğan ◽  
A. Muralikrishna Rao ◽  
Robert J. Dempsey
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Edema ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blue Dye ◽  
Neuroprotective Effects ◽  
Content Type ◽  
Blood Brain ◽  
Fine Print

Object. Cytidine 5′-diphosphocholine (CDPC), or citicoline, is a naturally occurring endogenous compound that has been reported to provide neuroprotective effects after experimental cerebral ischemia. However, in no study has such protection been shown after traumatic brain injury (TBI). In this study the authors examined the effect of CDPC on secondary injury factors, brain edema and blood-brain barrier (BBB) breakdown, after TBI.Methods. After anesthesia had been induced in Sprague—Dawley rats by using 1.5% halothane, an experimental TBI was created using a controlled cortical impact (CCI) device with a velocity of 3 m/second, resulting in a 2-mm deformation. Four sham-operated control animals used for brain edema and BBB breakdown studies underwent the same surgical procedure, but received no injury. Brain edema was evaluated using the wet—dry method 24 hours postinjury, and BBB breakdown was evaluated by measuring Evans blue dye (EBD) extravasation with fluorescein 6 hours after TBI. The animals received intraperitoneal injections of CDPC (50, 100, or 400 mg/kg two times after TBI [eight–10 animals in each group]) or saline (eight animals) after TBI. Traumatic brain injury induced an increase in the percentage of water content and in EBD extravasation in the injured cortex and the ipsilateral hippocampus. No significant benefit from CDPC treatment was observed at a dose of 50 mg/kg. Cytidine 5′-diphosphocholine at a dose of 100 mg/kg attenuated EBD extravasation in both regions, although it reduced brain edema only in the injured cortex. In both regions, 400 mg/kg of CDPC significantly decreased brain edema and BBB breakdown.Conclusions. This is the first report in which dose-dependent neuroprotective effects of CDPC have been demonstrated in the injured cortex as well as in the hippocampus, a brain region known to be vulnerable to injury, after experimental TBI. The results of this study suggest that CDPC is an effective neuroprotective agent on secondary injuries that appear following TBI.

scholarly journals Glycocalyx degradation leads to blood–brain barrier dysfunction and brain edema after asphyxia cardiac arrest in rats

2017 ◽  
Vol 38 (11) ◽  
pp. 1979-1992 ◽  
Author(s):  
Jiajia Zhu ◽  
Xing Li ◽  
Jia Yin ◽  
Yafang Hu ◽  
Yong Gu ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Survival Rate ◽  
Brain Edema ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Neurologic Outcome ◽  
Endothelial Glycocalyx ◽  
Inflammatory Factors ◽  
Blood Brain ◽  
Bbb Permeability

The role of glycocalyx in blood–brain barrier (BBB) integrity and brain damage is poorly understood. Our study aimed to investigate the impacts of endothelial glycocalyx on BBB function in a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Male Sprague-Dawley rats subjected to 8-min asphyxia CA/CPR. Compared to controls, glycocalyx was mildly injured by CA, severely disrupted by hyaluronidase (HAase) with CA, and mitigated by hydrocortisone (HC) with CA. More importantly, the disruption of glycocalyx caused by HAase treatment was associated with higher BBB permeability and aggravated brain edema at 24 h after return of spontaneous circulation, as well as lower survival rate and poorer neurologic outcome at seventh day. Reversely, less degradation of glycocalyx by HC treatment was accompanied by higher seven-day survival rate and better neurologic outcome. Mechanistically, HAase treatment further increased CA/CPR-induced activation of glia cells and expression of inflammatory factors, whereas HC decreased them in the brain cortex and hippocampus. Glycocalyx degradation results in BBB leakage, brain edema, and deteriorates neurologic outcome after asphyxia CA/CPR in rats. Preservation of glycocalyx by HC could improve neurologic outcome and reduce BBB permeability, apparently through reduced gene transcription-protein synthesis and inflammation.

Quantification and pharmacokinetics of blood-brain barrier disruption in humans

1996 ◽  
Vol 85 (6) ◽  
pp. 1056-1065 ◽  
Author(s):  
Bernhard Zünkeler ◽  
Richard E. Carson ◽  
Jeff Olson ◽  
Ronald G. Blasberg ◽  
Hetty Devroom ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Normal Brain ◽  
Content Type ◽  
Barrier Disruption ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Brain Barrier Disruption ◽  
Fine Print

✓ Hyperosmolar blood-brain barrier disruption (HBBBD), produced by infusion of mannitol into the cerebral arteries, has been used in the treatment of brain tumors to increase drug delivery to tumor and adjacent brain. However, the efficacy of HBBBD in brain tumor therapy has been controversial. The goal of this study was to measure changes in vascular permeability after HBBBD in patients with malignant brain tumors. The permeability (K1) of tumor and normal brain blood vessels was measured using rubidium-82 and positron emission tomography before and repeatedly at 8- to 15-minute intervals after HBBBD. Eighteen studies were performed in 13 patients, eight with glioblastoma multiforme and five with anaplastic astrocytoma. The HBBBD increased K1 in all patients. Baseline K1 values were 2.1 ± 1.4 and 34.1 ± 22.1 µl/minute/ml (± standard deviation) for brain and tumor, respectively. The peak absolute increases in K1 following HBBBD were 20.8 ± 11.7 and 19.7 ± 10.7 µl/minute/ml for brain and tumor, corresponding to percentage increases of approximately 1000% in brain and approximately 60% in tumor. The halftimes for return of K1 to near baseline for brain and tumor were 8.1 ± 3.8 and 4.2 ± 1.2 minutes, respectively. Simulations of the effects of HBBBD made using a very simple model with intraarterial methotrexate, which is exemplary of drugs with low permeability, indicate that 1) total exposure of the brain and tumor to methotrexate, as measured by the methotrexate concentration-time integral (or area under the curve), would increase with decreasing infusion duration and would be enhanced by 130% to 200% and by 7% to 16%, respectively, compared to intraarterial infusion of methotrexate alone; and 2) exposure time at concentrations above 1 µM, the minimal concentration required for the effects of methotrexate, would not be enhanced in tumor and would be enhanced by only 10% in brain. Hyperosmolar blood-brain barrier disruption transiently increases delivery of water-soluble compounds to normal brain and brain tumors. Most of the enhancement of exposure results from trapping the drug within the blood-brain barrier, an effect of the very transient alteration of the blood-brain barrier by HBBBD. Delivery is most effective when a drug is administered within 5 to 10 minutes after disruption. However, the increased exposure and exposure time that occur with methotrexate, the permeability of which is among the lowest of the agents currently used clinically, are limited and the disproportionate increase in brain exposure, compared to tumor exposure, may alter the therapeutic index of many drugs.

Quantitative autoradiographic measurements of blood-brain barrier permeability in the rat glioma model

1982 ◽  
Vol 57 (3) ◽  
pp. 394-398 ◽  
Author(s):  
Kazuo Yamada ◽  
Yukitaka Ushio ◽  
Toru Hayakawa ◽  
Amami Kato ◽  
Noriko Yamada ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Chemotherapeutic Drugs ◽  
Content Type ◽  
Rat Glioma ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
Bbb Permeability ◽  
Autoradiographic Technique ◽  
The Brain

✓ Quantitative autoradiographic technique was applied in measuring blood-brain barrier (BBB) permeability of autochthonous gliomas in rats. In small tumors (less than 2 mm in diameter), no increase in BBB permeability was noted. As the tumor grew and neovascularization occurred, BBB permeability increased in the center of the tumor, and it was suggested that the BBB was partly disrupted in the neovascularized vessels. In the fully grown tumors, BBB permeability was markedly increased in the viable part of the tumor to levels similar to the choroid plexus. Yet, the BBB was partly preserved at the periphery of the tumor and in the brain adjacent to the tumor. The heterogeneity of the BBB phenomenon according to the stage of tumor growth may be a major obstacle for uptake of chemotherapeutic drugs that do not cross the BBB easily.

Penetration of recombinant interleukin-2 across the blood-cerebrospinal fluid barrier

1988 ◽  
Vol 69 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Stephen C. Saris ◽  
Steven A. Rosenberg ◽  
Robert B. Friedman ◽  
Joshua T. Rubin ◽  
David Barba ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Blood Brain Barrier ◽  
Interleukin 2 ◽  
Albumin Level ◽  
Brain Barrier ◽  
Lymphokine Activated Killer Cells ◽  
Content Type ◽  
Blood Brain ◽  
Recombinant Interleukin 2 ◽  
Fine Print

✓ Recombinant interleukin-2 (rIL-2) is an immunotherapeutic agent with efficacy against certain advanced cancers. The penetration of rIL-2 across the blood-cerebrospinal fluid (CSF) barrier was studied in 12 cancer patients who had no evidence of tumor involvement of the central nervous system. At different times during treatment with intravenous rIL-2, CSF was withdrawn either continuously for 8 to 26 hours via a lumbar subarachnoid catheter (in eight patients) or by a single lumbar puncture (in four). Bioassay showed the appearance of rIL-2 in lumbar CSF 4 to 6 hours after the first intravenous dose, a rise over 2 to 4 hours to a plateau of 3 to 9 U/ml, and clearance to less than 0.1 U/ml by 10 hours after the last dose. An abnormally elevated CSF albumin level in two of the twelve patients indicated alteration of the blood-brain barrier. There were no abnormalities in the CSF glucose level or white blood cell count. The CSF pharmacokinetics contrast with the rapid elimination of rIL-2 from plasma and demonstrate significant blood-CSF barrier penetration. These data support the possibility of achieving CSF levels of rIL-2 that are adequate to maintain activity of lymphokine-activated killer cells after parenteral administration, and argue for rIL-2-associated disruption of the human blood-brain barrier in some patients.

Selective blood-tumor barrier disruption by leukotrienes

1992 ◽  
Vol 77 (3) ◽  
pp. 407-410 ◽  
Author(s):  
Chung-Ching Chio ◽  
Takehiko Baba ◽  
Keith L. Black
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Normal Brain ◽  
Barrier Permeability ◽  
Content Type ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
The Mean ◽  
Fine Print

✓ The authors have previously reported that intracarotid infusion of 5 µg leukotriene C4 (LTC4) selectively increases blood-tumor barrier permeability in rat RG-2 tumors. In this study, rats harboring RG-2 tumors were given 15-minute intracarotid infusions of LTC4 at concentrations ranging from 0.5 µg to 50.0 µg (seven rats in each dose group). Blood-tumor and blood-brain barrier permeability were determined by quantitative autoradiography using 14C aminoisobutyric acid. The transfer constant for permeability (Ki) within the tumors was increased twofold by LTC4 doses of 2.5, 5.0, and 50.0 µg compared to vehicle alone (90.00 ±21.14, 92.68 ± 15.04, and 80.17 ± 16.15 vs. 39.37 ± 6.45 µl/gm/min, respectively; mean ± standard deviation; p < 0.01). No significant change in Ki within the tumors was observed at the 0.5-µg LTC4 dose. Blood-brain barrier permeability was selectively increased within the tumors. At no dose in this study did leukotrienes increase permeability within normal brain. To determine the duration of increased opening of the blood-tumor barrier by LTC4 administration, Ki was measured at 15, 30, and 60 minutes after termination of a 15-minute LTC4 infusion (seven rats at each time point). The mean Ki value was still high at 15 minutes (92.68 ± 15.04 µl/gm/min), but declined at 30 minutes (56.58 ± 12.50 µl/gm/min) and 60 minutes (55.40 ± 8.10 µl/gm/min) after the end of LTC4 infusion. Sulfidopeptide leukotrienes LTC4, LTD4, LTE4 and LTF4 were infused to compare their potency in opening the blood-tumor barrier. The mean leukotriene E4 was the most potent, increasing the permeability value 37½ fold compared with vehicle alone (139.86 ± 23.95 vs. 39.37 ± 6.45 µl/gm/min).

The effect of interleukin-2 on the blood-brain barrier in the 9L gliosarcoma rat model

1989 ◽  
Vol 70 (1) ◽  
pp. 92-96 ◽  
Author(s):  
Joseph T. Alexander ◽  
Stephen C. Saris ◽  
Edward H. Oldfield
Keyword(s):  
Blood Brain Barrier ◽  
Interleukin 2 ◽  
Brain Barrier ◽  
High Dose ◽  
Normal Brain ◽  
Content Type ◽  
Tumor Bearing ◽  
Blood Brain ◽  
Significant Difference ◽  
Fine Print

✓ Carbon-14-labeled aminoisobutyric acid was used to determine local blood-to-tissue transfer constants in 22 Fischer rats with intracerebral 9L gliosarcomas that received either high-dose parenteral interleukin-2 (IL-2) or a control injection. In tumor and peritumoral tissue, the transfer constants in the IL-2-treated animals (89.6 ± 14.6 and 35.8 ± 6.0, respectively, mean ± standard error of the mean) were larger (p < 0.05) than in control animals (61.4 ± 6.4 and 14.6 ± 2.2, respectively). In contrast, in normal frontal and occipital tissue contralateral to the tumor-bearing hemisphere, there was no significant difference between the transfer constants in IL-2-treated and control animals. Furthermore, treatment of animals with IL-2 excipient caused no change in permeability as compared to animals treated with Hanks' balanced salt solution. Parenteral injection of IL-2 increases blood-brain barrier disruption in tumor-bearing rat brain but does not increase the vascular permeability of normal brain. Methods to prevent this increased tumor vessel permeability are required before parenteral IL-2 can be used safely for the treatment of primary or metastatic brain tumors.

Cerebrovascular permeability and delivery of gentamicin to normal brain and experimental brain abscess in rats

1984 ◽  
Vol 61 (3) ◽  
pp. 430-439 ◽  
Author(s):  
Edward A. Neuwelt ◽  
David E. Baker ◽  
Michael A. Pagel ◽  
Nathan K. Blank
Keyword(s):  
Brain Abscess ◽  
Blood Brain Barrier ◽  
Medical Management ◽  
Brain Barrier ◽  
High Dose ◽  
Normal Brain ◽  
Content Type ◽  
Stage Of Development ◽  
Blood Brain ◽  
Brain Abscesses

✓ Antibiotics vary widely in their ability to penetrate the blood-brain barrier. In studies of 70 rats, the permeability of the normal blood-brain barrier to gentamicin was shown to be poor. In experimental brain abscesses, during the cerebritic stage of development, the penetration of intravenous antibiotics was increased compared to normal brain but was very inconsistent. Antibiotic delivery to brain abscess was not significantly altered with the administration of high-dose steroids, but the macrophage and glial response was markedly decreased with high-dose steroid therapy. Reversible osmotic blood-brain barrier modification with mannitol increased the delivery of gentamicin both to brain abscess and to the surrounding brain. It also resulted in more consistent tissue drug levels. The clinical implications of these studies suggest that, because of the inconsistent delivery of gentamicin to brain abscess, the therapeutic efficacy of medical management alone may be quite variable. This mode of therapy could possibly increase the efficacy of medical management of brain abscesses, especially in patients with multiple or surgically inaccessible brain abscesses.

In vivo assessment of the window of barrier opening after osmotic blood—brain barrier disruption in humans

2000 ◽  
Vol 92 (4) ◽  
pp. 599-605 ◽  
Author(s):  
Tali Siegal ◽  
Rina Rubinstein ◽  
Felix Bokstein ◽  
Allan Schwartz ◽  
Alexander Lossos ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Time Course ◽  
Photon Emission ◽  
Brain Barrier ◽  
Therapeutic Window ◽  
Content Type ◽  
Blood Brain ◽  
The Mean ◽  
Fine Print

Object. Osmotic blood—brain barrier (BBB) disruption induced by intraarterial infusion of mannitol is used in conjunction with chemotherapy to treat human brain tumors. The time course to barrier closure, or the so-called therapeutic window, has been examined in animals but little information is available in humans. The authors, therefore assessed the time course to barrier closure after osmotic BBB disruption in humans.Methods. Disruption of the BBB was demonstrated using 99mTc-glucoheptonate (TcGH) single-photon emission computerized tomography (SPECT) scanning in 12 patients who were treated monthly with combination chemotherapy in conjunction with BBB disruption. The primary diagnosis was primary central nervous system lymphoma in seven patients and primitive neuroectodermal tumors in five. The TcGH (20 mCi) was injected at 1- to 480-minute intervals after osmotic BBB disruption, and patients underwent SPECT scanning after 4 hours. A total of 38 studies was performed. Good-to-excellent BBB disruption was obtained in 29 procedures and poor-to-moderate disruption was seen in the other nine studies.The TcGH indices correlated with the degree of BBB disruption as measured postprocedure on contrast-enhanced CT scans (r = 0.852). Mean baseline TcGH indices were 1.02 ± 0.07. For the group of patients with good-to-excellent disruptions the mean indices at 1 minute postdisruption measured 2.19 ± 0.18. After 40 minutes no significant change was noted (mean index 2.13 ± 0.2). Then the indices declined more steeply and at 120 minutes after the disruption the index was 1.36 ± 0.02. A very slow decline was noted between 120 and 240 minutes after mannitol infusion. At 240 minutes the barrier was still open for all good-to-excellent disruptions (index 1.33 ± 0.08) but at 480 minutes the mean indices had returned to the baseline level.Conclusions. Results of these in vivo human studies indicate that the time course to closure of the disrupted BBB for low-molecular-weight complexes is longer than previously estimated. The barrier is widely open during the first 40 minutes after osmotic BBB disruption and returns to baseline levels only after 6 to 8 hours following the induction of good or excellent disruption. These findings have important clinical implications for the design of therapeutic protocols.

Temporary cortical blindness following angiography

1974 ◽  
Vol 40 (5) ◽  
pp. 583-586 ◽  
Author(s):  
Norman H. Horwitz ◽  
Louis Wener
Keyword(s):  
Blood Brain Barrier ◽  
Striate Cortex ◽  
Cortical Blindness ◽  
Brain Barrier ◽  
Content Type ◽  
Blood Brain ◽  
Theoretical Considerations ◽  
Fine Print

✓ Temporary cortical blindness as a complication of posterior angiography is reported in 11 patients and compared with 30 similar cases previously reported. Theoretical considerations of etiology implicate transitory alterations of the blood-brain barrier in the striate cortex.

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