Oxygen Free Radicals and the Cerebral Arteriolar Response to Group B Streptococci

McKnight, Áine; Keyes, William G.; Hudak, Mark L.; Jones, Mathew

doi:10.1203/00006450-199206000-00020

Cited by 44 publications

(23 citation statements)

References 11 publications

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“…The colocalization of ROI production with cerebral blood vessels suggests that ROI may contribute to the changes of cerebral blood flow observed during bacterial meningitis (10,47). In a study in rats using a cranial window preparation, exposure of pial arterioles to live and killed GBS produced a marked and progressive vasodilatation which was prevented by ROI scavengers (11). Similarly, ROI scavengers reduced the early hyperemia and brain edema in an adult rat model of pneumococcal meningitis (35).…”

Section: Discussionmentioning

confidence: 99%

“…The pronounced ROI production associated with the cerebral vasculature and the marked restitution of cerebral cortical perfusion by PBN in our model indicate that ROI play a critical role in the vascular events during meningitis that lead to cerebral hypoperfusion. Processes that may be attenuated by inactivation of ROI through scavenging with PBN include vasomotor responses, leukocyte-endothelial cell interactions, platelet activation, and intracranial pressure (11,35,44,54). The improvement of cerebral perfusion resulting from scavenging of ROI conceivably is an important reason for the neuroprotective effect of PBN in the present model, particularly when PBN was started at the time of infection and thus largely prevented the development of cerebral ischemia.…”

Section: Discussionmentioning

confidence: 99%

“…Inflammation has been strongly linked to the development of brain injury in experimental models of meningitis, and the major inflammatory cells in bacterial meningitis are neutrophilic granulocytes, which are potent generators of ROI (1). Inflammatory involvement of the cerebral vasculature has been suggested to be a major contributor to ischemic brain injury during meningitis (10), and cerebral vascular reactivity has been shown to be modulated by ROI in experimental meningitis (11,12). Finally, neuronal injury in meningitis is in part caused by increased concentrations of excitatory amino acid (13,14), and the neurotoxic effect of excitatory amino acids has been clearly linked to the generation of ROI (15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

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Reactive oxygen intermediates contribute to necrotic and apoptotic neuronal injury in an infant rat model of bacterial meningitis due to group B streptococci.

Leib¹,

Kim²,

Chow³

et al. 1996

J. Clin. Invest.

219

159

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Reactive oxygen intermediates contribute to necrotic and apoptotic neuronal injury in an infant rat model of bacterial meningitis due to group B streptococci.

Leib¹,

Kim²,

Chow³

et al. 1996

J. Clin. Invest.

219

159

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“…SOD may act by preventing the formation of toxic peroxynitrite from superoxide anion radical and nitric oxide [41]. Pfister cited results from studies by McKnight et al [50] documenting an increase in pial arteriolar diameter following the topical application of group B streptococci to the brain surface in rats. Treatment with iv PEG-SOD (10,000 U/kg) and PEG-catalase (20,000 U/kg) before exposure to group B streptococci prevented vasodilation; this result indirectly supports a role for reactive oxygen species.…”

Section: Molecular Mechanisms Of Neuronal Injurymentioning

confidence: 98%

Mechanisms of Brain Injury in Bacterial Meningitis: Workshop Summary

Pfister

Fontana²,

Täuber³

et al. 1994

Clinical Infectious Diseases

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Morbidity and mortality associated with bacterial meningitis remain high, although antibiotic therapy has improved during recent decades. The major intracranial complications of bacterial meningitis are cerebrovascular arterial and venous involvement, brain edema, and hydrocephalus with a subsequent increase of intracranial pressure. Experiments in animal models and cell culture systems have focused on the pathogenesis and pathophysiology of bacterial meningitis in an attempt to identify the bacterial and/or host factors responsible for brain injury during the course of infection. An international workshop entitled "Bacterial Meningitis: Mechanisms of Brain Injury" was organized by the Department of Neurology at the University of Munich and was held in Eibsee, Germany, in June 1993. This conference provided a forum for the exchange of current information on bacterial meningitis, including data on the clinical spectrum of complications, the associated morphological alterations, the role of soluble inflammatory mediators (in particular cytokines) and of leukocyte-endothelial cell interactions in tissue injury, and the molecular mechanisms of neuronal injury, with potential mediators such as reactive oxygen species, reactive nitrogen species, and excitatory amino acids. It is hoped that a better understanding of the pathophysiological events that take place during bacterial meningitis will lead to the development of new therapeutic regimens.Although the recent licensure of Haeniophilus influenzae type b (Hib) polysaccharide conjugate protein vaccines has had a marked impact on the incidence of invasive Hib disease in the United States and Western Europe. bacterial meningitis overall remains a significant problem worldwide. In addition, despite the introduction of new antimicrobial agents and improved diagnostic techniques, the mortality and morbidity associated with bacterial meningitis remain unacceptably high. This discrepancy between a rapid bacteriologic response at the site of infection (i.e .. eradication of viable bacteria from the CSF due to treatment with potent bactericidal agents) and the persistence of the associated neurological sequelae and mortality has prompted intense investigation over the past two decades into the pathophysiology of this disease. Indeed. recent clinical studies have employed adjunctive agents (e.g .. dexamethasone) in an attempt to reduce mortality and alleviate neurological sequelae [1][2][3][4]. These studies and the resulting recommendations regarding the use of adjunctive dexamethasone have recently been reviewed [5.6].In line with the current emphasis on the pathogenesis and pathophysiology of bacterial meningitis. two workshops were held in California in the 1980s [7]. Recognizing that many advances have been made in this field in the several years since those meetings. the Department of Neurology at the University of Munich organized a similar workshop, which was held in Eibsce. Germanv. on 25 and 26 June 1993. As IS evident from its title-"Bacterial Meningitis: Mechanisms...

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“…prostaglandin E2 (1 l, 12); cytokines, e.g. tumor necrosis factor and IL (1 1); or oxygenderived free radicals (10,13).…”

Section: Discussionmentioning

confidence: 99%

Haemophilus Influenzae Type B Impairment of Pial Vessel Autoregulation in Rats

et al. 1993

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ABSTRACT. To examine the mechanisms of autoregulatory impairment in meningitis, we studied the effects of Haemophilus influenzae type b (Hib) on pial vessels during hemorrhagic hypotension in rats, using a cranial window technique. We prepared cranial windows in barbiturateanesthetized, mechanically ventilated rats. Artificial cerebrospinal fluid or 10' Hib in cerebrospinal fluid (n = 7 each group) was suffused over the pial surface. Pial arteriolar diameter was measured hourly for 4 h. Autoregulation was assessed as the ability of pial arterioles to dilate in response to graded hemorrhagic hypotension at 2 and 4 h. Pial arterioles exposed to Hib dilated progressively to 149 2 27% of baseline at 4 h. Vessel diameter in the Hib group was significantly greater than in the control group beginning at 2 h. Autoregulation was progressively impaired in Hib-exposed rats compared with control rats 1-5. 85 (1) and and animals (2) with acute bacterial meningitis. Such impairment could contribute to the high incidence of neurologic morbidity and the high mortality rate of this disease (3, 4) by decreasing cerebral blood flow under circumstances of only a modest reduction of cerebral perfusion pressure. Mechanisms of autoregulatory impairment are, however, unknown.Blood vessels coursing over the brain surface are likely to be particularly vulnerable to the effects of bacteria and inflammation. Therefore, to examine the roles of both cortical microcirculatory dilation and vasoparesis in the autoregulatory impairment of meningitis, we studied the effects of Hib on pial vessels during hemorrhagic hypotension in rats, using a cranial window technique. MATERIALS AND METHODSAnimal preparation. Cranial window. Cranial windows were constructed with modifications of the technique described by Morii et al. (5). After the cranium was secured in a stereotactic frame, the skull was exposed by excising skin, fascia, and periosteum from forehead to occiput. Hemostasis was achieved with ferric-chloride-soaked cotton pledgets. The residual ferric chloride was then thoroughly removed with normal saline irrigation. Two lengths of polyethylene tubing (PE90) for perfusion of artificial CSF and measurement of intracranial pressure were passed through drilled holes in a 7-mm diameter, 1.5-mm-thick plastic ring cut from the barrel of a 5-mL plastic syringe. The ring was then cemented to the skull over the parietal bone with dental acrylic. A craniotomy to remove an approximately 3-X 4-mm segment of parietal bone. within the area enclosed bv the ring, was ~erformed under a midroscope with an air-cooledhental drill. ~f t e r the bone flap was removed, the underlying dura and arachnoid were incised with a 27-gauge needle and removed with microforceps. Hemostasis was obtained by crushing the vessels at the free edge of the dura with microforceps. Artificial CSF fluid (5) (Na' 156.5 mmol/L, K+ 2.95 mmol/L, Ca2+ 2.50 mmol/L, Mg2+ 1.33 mmol/L, C1-138.7 mmol/L, HC03-24.6 mmol/L, dextrose 3.69 mmol/L, and urea 6.69 mmol/L) was aerated with 5% C 0 2 in a...

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Oxygen Free Radicals and the Cerebral Arteriolar Response to Group B Streptococci

Cited by 44 publications

References 11 publications

Reactive oxygen intermediates contribute to necrotic and apoptotic neuronal injury in an infant rat model of bacterial meningitis due to group B streptococci.

Reactive oxygen intermediates contribute to necrotic and apoptotic neuronal injury in an infant rat model of bacterial meningitis due to group B streptococci.

Mechanisms of Brain Injury in Bacterial Meningitis: Workshop Summary

Haemophilus Influenzae Type B Impairment of Pial Vessel Autoregulation in Rats

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