Abstract | BACKGROUND AND PURPOSE: Microglial activation may contribute to the pathogenesis of the brain injury in intracerebral hemorrhage (ICH). We have reported that the tripeptide macrophage/microglial inhibitory factor (MIF), Thr-Lys-Pro, inhibits microglial activation and results in functional improvement when given before the onset of hemorrhage. In this study, we investigate the protection and efficacy of treatment when MIF is administered 2 hours after collagenase injection. METHODS: ICH was induced by injecting bacterial collagenase into the caudate nucleus; 100 microL MIF (500 micromol/L) was delivered via a micro-osmotic pump. Infusion of MIF or saline (control) was initiated 2 hours after collagenase injection and continued for 24 or 72 hours. Microglial activation and macrophage infiltration were assessed by 5-d-4 and F4/80 immunofluorescence, respectively. Production of reactive oxygen species was visualized by in situ detection of ethidium. Degenerating neurons were assessed by Fluoro-Jade B staining. Neurological deficits, brain injury volumes, and brain edema were assessed at 24 and 72 hours after MIF/saline treatment. RESULTS: MIF can inhibit microglial activation and macrophage infiltration, attenuate the numbers of ethidium-positive cells compared with the saline-treated control mice, reduce the injury volume, edema, and degenerating neurons, and improve the neurological functional outcome. CONCLUSIONS: Activated microglia/macrophages are important contributors to brain injury after ICH. MIF could be a valuable neuroprotective agent for the treatment of ICH, if treatment is initiated soon after the onset of hemorrhage.
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Authors | Jian Wang, Stella E Tsirka |
Journal | Stroke
(Stroke)
Vol. 36
Issue 3
Pg. 613-8
(Mar 2005)
ISSN: 1524-4628 [Electronic] United States |
PMID | 15692122
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Macrophage Migration-Inhibitory Factors
- Peptide Fragments
- Reactive Oxygen Species
- Collagenases
- Tuftsin
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Topics |
- Animals
- Brain Injuries
(prevention & control)
- Caudate Nucleus
(pathology)
- Cell Death
(drug effects)
- Cerebral Hemorrhage
(chemically induced, complications)
- Collagenases
(adverse effects)
- Edema
(metabolism)
- Macrophage Migration-Inhibitory Factors
(metabolism, physiology, therapeutic use)
- Macrophages
(metabolism)
- Mice
- Mice, Inbred C57BL
- Microglia
(physiology)
- Neurons
(drug effects)
- Peptide Fragments
(therapeutic use)
- Psychomotor Disorders
(etiology, prevention & control)
- Reactive Oxygen Species
(metabolism)
- Stroke Volume
(drug effects)
- Tuftsin
(therapeutic use)
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