Cortical Microcirculation in a New Model of Focal Laser-Induced Secondary Brain Damage

Lindsberg, Perttu J.; Frerichs, Kai U.; Burris, J A; Hallenbeck, John M.; Feuerstein, Giora

doi:10.1038/jcbfm.1991.10

Cited by 29 publications

(8 citation statements)

References 25 publications

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“…Since cerebral accumulation of indium (" 'In)-labeled platelets failed to decrease, the treatment effect was concluded to be independent of platelets. In a new focal model of laserinduced secondary brain damage in rats, where a regular penumbral zone of ischemia, BBB damage, and edema develops surrounding a core of irreversible cortical neuronal necrosis [83], PAF antagonist (BN 50739) improved the penumbral CBF and edema and ameliorated the delayed neuronal necrosis, which otherwise extended into the vulnerable CA 1 hippocampal area [84]. Neutrophil accumulation in areas undergoing secondary brain damage was also reduced.…”

Section: Models Of Focal Cerebral Ischemiamentioning

confidence: 99%

Platelet‐activating factor in stroke and brain injury

Lindsberg

Hallenbeck

Feuerstein

1991

Annals of Neurology

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139

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Platelet-activating factor, an endogenous phospholipid of proinflammatory, hemostatic, and vasoactive properties, is synthesized by neurons and in injured brain. Platelet-activating factor is released together with eicosanoids such as thromboxane A2, prostacyclin, and leukotrienes. Its effects in neurons are mediated through a specific receptor coupled to phospholipase C and phosphoinositol metabolism. The cerebrovascular effects of platelet-activating factor include disruption of the blood-brain barrier, edema formation, and vasospasm. It has also been described to possess direct toxicity to neuronal cells in culture. Discovery and development of several highly potent and selective antagonists to platelet-activating factor receptors facilitated experimental studies underscoring the role of this factor as an endogenous mediator in cerebral disorders, particularly cerebral ischemia and trauma. Significant biochemical, microvascular, functional, and behavioral recovery has been demonstrated using these antagonists in an array of experimental models of focal and global ischemia in the central nervous system (CNS). Clearly, studies of platelet-activating factor in experimental models of CNS ischemia and reperfusion injury open a new perspective on phospholipid metabolism in stroke and offer an exceptionally promising therapeutic prospect. Data supporting this factor as a mediator of specific pathological sequelae in stroke and neuroinjury are surveyed in this review. We discuss the mechanisms and significance of platelet-activating factor-mediated effects and propose directions for future studies.

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Section: Models Of Focal Cerebral Ischemiamentioning

confidence: 99%

Platelet‐activating factor in stroke and brain injury

Lindsberg

Hallenbeck

Feuerstein

1991

Annals of Neurology

Self Cite

139

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“…Inhibition of the early and delayed postischemic hypoperfusion by the PAF antagonist is in agreement with our previous observation demonstrating perturbation of the rabbit spinal cord microcirculation by exogenous PAF. 24 During postischemic hypoperfusion following forebrain ischemia in gerbils and in a new model of laser-induced focal penumbral microcirculatory failure in rats, 25 similar beneficial effects of PAF antagonism were demonstrated, but not in association with PAF production. 26 - 27 However, PAF levels comparable to our results have been detected in rat brain injured by chemically induced convulsions.…”

Section: Discussionmentioning

confidence: 90%

Evidence for platelet-activating factor as a novel mediator in experimental stroke in rabbits.

Lindsberg

Yue

Frerichs

et al. 1990

Stroke

100

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Platelet-activating factor is a potent mediator of inflammation, which has untoward effects on cerebrovascular and neural elements. While several investigators have reported attenuation of ischemic damage after treatment with antagonists of platelet-activating factor, no study has proved endogenous production of platelet-activating factor in ischemia of the central nervous system. We hypothesized that endogenous production of platelet-activating factor participates in the early pathologic manifestations of deteriorating stroke. In 12 rabbits, we found tissue levels of platelet-activating factor measured by the release of serotonin from washed

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“…More recent findings indicate that any primary necrosis of brain parenchyma evolving from a focal traumatic insult is subject to secondary growth. A variety of experiments utilizing different trauma models in various species have consistently shown that the size of a focal tissue necrosis increases within 24 h. The observed "growth" has been reported between 130 and 400 % of the initial lesion (Eggert et al, 1985;Lindsberg et al, 1991;Vonhof, 1997;Wyrwich, 1997;Murakami et al, 1999). A study from our laboratory has followed the growth kinetics of a focal cortical lesion at 5 min, and 3, 6, 12, 18, and 24 h after freezing injury in the rat by means of histology (Eriskat et al, 1994).…”

Section: Introductionmentioning

confidence: 94%

Release of Excitatory Amino Acids in the Penumbra of a Focal Cortical Necrosis

Stoffel

Plesnila

Eriskat

et al. 2002

Journal of Neurotrauma

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A cortical tissue necrosis from focal trauma expands between 30% and 300% from its initial size within 24 h, depending on the species studied. To shed light on the pathophysiological processes in the penumbra 1 zone after a focal cortical lesion, the release of excitatory amino acids into the traumatic penumbra zone 1 was measured throughout the entire period of necrosis expansion. A microdialysis probe was inserted at an oblique angle into the cortex of Sprague-Dawley rats 2 mm below the brain surface. One day later, a highly standardized cortical freezing lesion was induced at the brain cortex above the microdialysis probe. Dialysate was continuously collected prior to, during, and up to 24 h after trauma and analyzed for primary amino acids. In each animal, it was confirmed histologically that the tip of the microdialysis probe was localized in the gray matter in close proximity to the primary lesion. Following induction of the trauma, a statistically significant sharp increase of the dialysate level of aspartate, glutamate, glycine, and serine was observed. Thereafter, the dialysate levels of these amino acids returned to baseline levels without any further increase throughout the remaining observation period. This process ranged in time from a few minutes to a few hours. The level of alanine in the dialysate was essentially not altered throughout the experiment. Although the early post-traumatic increase of the excitatory neurotransmitters aspartate and glutamate may well contribute to the secondary lesion growth of a cortical necrosis after trauma, glutamate receptor targeted therapeutic intervention may be in view of these findings of limited use when initiated post trauma.

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Cortical Microcirculation in a New Model of Focal Laser-Induced Secondary Brain Damage

Cited by 29 publications

References 25 publications

Platelet‐activating factor in stroke and brain injury

Platelet‐activating factor in stroke and brain injury

Evidence for platelet-activating factor as a novel mediator in experimental stroke in rabbits.

Release of Excitatory Amino Acids in the Penumbra of a Focal Cortical Necrosis

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