Reduction of central nervous system reperfusion injury in rabbits using doxycycline treatment.

Clark, Wayne M.; Calcagno, Frank A.; Gabler, W. L.; Smith, John R. Lindsay; Coull, Bruce M.

doi:10.1161/01.str.25.7.1411

Cited by 43 publications

(22 citation statements)

References 31 publications

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“…Meanwhile, in reference to the spinal cord, Clark et al 40 reported that paraplegia in animals decreased when doxycycline, which inhibited leukocyte function and adhesion in vitro, was administered before ischemia rather than after ischemia. In the present study leukocyte adhesion was also observed in the early phase after MCAO, and it was suppressed by moderate hypothermia.…”

Section: Effect Of Hypothermia On Leukocyte Adhesion In Venulesmentioning

confidence: 99%

Effects of Moderate Hypothermia on Leukocyte- Endothelium Interaction in the Rat Pial Microvasculature After Transient Middle Cerebral Artery Occlusion

Ishikawa

Sekizuka

Sato

et al. 1999

Stroke

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Background and Purpose-It has been demonstrated that moderate hypothermia attenuates brain damage, but the mechanism whereby this is achieved has not been clearly shown. Recently, the role of leukocytes as mediators of secondary brain damage after brain ischemia has been discussed. The aim of this study is to examine the effects of moderate hypothermia on leukocyte-endothelium interaction in the rat pial microvasculature after transient middle cerebral artery occlusion (MCAO). Methods-Rhodamine 6G-labeled leukocytes in brain surface were visualized with intravital fluorescence videomicroscopy through a closed cranial window. We analyzed the number of leukocytes adhering to the venular and arteriolar endothelium before ischemic insult and up to 3 hours after reperfusion. Rats were divided into 4 experimental groups. Group I (nϭ6) consisted of sham-operated animals. Groups II (nϭ6) and III (nϭ6) received left MCAO for 1 hour under normothermia (36°C to 37°C, group II) and under moderate hypothermia (30°C to 32°C, group III). Group IV (nϭ4) received left common carotid artery occlusion for 1 hour under normothermia. Results-The number of adhering leukocytes in venules in groups II and IV increased significantly (PϽ0.001) after reperfusion compared with the group I, but that in group III did not increase significantly (PϾ0.05). The number of adhering leukocytes in arterioles in group II increased significantly (PϽ0.01) compared with the other groups, although the adhering leukocytes were not as numerous as those seen in venules. Conclusions-It is demonstrated that hypothermia attenuates adhering leukocytes in venules and arterioles after reperfusion of MCAO. The inhibition of the leukocyte function may be an important factor in the neuroprotective effect of hypothermia.

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Section: Effect Of Hypothermia On Leukocyte Adhesion In Venulesmentioning

confidence: 99%

Effects of Moderate Hypothermia on Leukocyte- Endothelium Interaction in the Rat Pial Microvasculature After Transient Middle Cerebral Artery Occlusion

Ishikawa

Sekizuka

Sato

et al. 1999

Stroke

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“…Outcome after cerebral ischemia is improved by antiinflammatory strategies, such as depleting the circulating pool of leukocytes (30,31), inhibiting leukocyte function (32), and blocking leukocyte adhesion (33,34), and by immunosuppressive drugs, such as high-dose steroids (35), cyclosporine A (1, 2), and FK506 (3,4). At present, however, there are no interventions that limit the CNS inflammatory response without also affecting systemic responses.…”

Section: Discussionmentioning

confidence: 99%

Immunologic tolerance to myelin basic protein decreases stroke size after transient focal cerebral ischemia

Becker

McCarron

Ruetzler

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

145

108

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Immune mechanisms contribute to cerebral ischemic injury. Therapeutic immunosuppressive options are limited due to systemic side effects. We attempted to achieve immunosuppression in the brain through oral tolerance to myelin basic protein (MBP). Lewis rats were fed low-dose bovine MBP or ovalbumin (1 mg, five times) before 3 h of middle cerebral artery occlusion (MCAO). A third group of animals was sensitized to MBP but did not survive the post-stroke period. Infarct size at 24 and 96 h after ischemia was significantly less in tolerized animals. Tolerance to MBP was confirmed in vivo by a decrease in delayed-type hypersensitivity to MBP. Systemic immune responses, characterized in vitro by spleen cell proliferation to Con A, lipopolysaccharide, and MBP, again confirmed antigen-specific immunologic tolerance. Immunohistochemistry revealed transforming growth factor ␤1 production by T cells in the brains of tolerized but not control animals. Systemic transforming growth factor ␤1 levels were equivalent in both groups. Corticosterone levels 24 h after surgery were elevated in all sham-operated animals and ischemic control animals but not in ischemic tolerized animals. These results demonstrate that antigen-specific modulation of the immune response decreases infarct size after focal cerebral ischemia and that sensitization to the same antigen may actually worsen outcome.

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“…An inhibition of the MMP-9 pathway was described for both minocycline and doxycycline [135,136]. Minocycline has been shown to be neuroprotective in several adult animal models of neurological disorders [137,138,139,140,141,142,143,144]. Similarly, minocycline has been reported to be neuroprotective in developing brain damage models such as hypoxia-ischemia in neonatal or juvenile rats [145,146,147,148,149,150] and excitotoxic perinatal brain damage in mice [69].…”

Section: The Bad Guys? Microglia and Neurodegenerationmentioning

confidence: 99%

The Yin and Yang of Microglia

2011

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Microglia, the resident immune cells of the mammalian central nervous system (CNS), play a pivotal role in both physiological and pathological conditions such as the restoration of CNS integrity and the progression of neurodegenerative disorders. Extensive data have been published that describe neuroinflammation by microglial activation to have detrimental consequences on the developing and mature brain. On the other hand, a properly directed and limited inflammatory response is known to be a natural healing process after an insult in several other tissues. Thus, it is not surprising that research results illustrating benefits of neuroinflammation have been emerging over the past decade. Inflammation-mediated benefits for CNS outcomes include mechanisms such as neuroprotection, mobilization of neural precursors for repair, remyelination and axonal regeneration. Here, we review data that highlight the dual aspects of microglia with a focus on the developing brain, i.e. as aggressors potentiating damage and as helpers in the recovery process following CNS damage.

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Reduction of central nervous system reperfusion injury in rabbits using doxycycline treatment.

Cited by 43 publications

References 31 publications

Effects of Moderate Hypothermia on Leukocyte- Endothelium Interaction in the Rat Pial Microvasculature After Transient Middle Cerebral Artery Occlusion

Effects of Moderate Hypothermia on Leukocyte- Endothelium Interaction in the Rat Pial Microvasculature After Transient Middle Cerebral Artery Occlusion

Immunologic tolerance to myelin basic protein decreases stroke size after transient focal cerebral ischemia

The Yin and Yang of Microglia

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