Tuftsin fragment 1-3 is beneficial when delivered after the induction of intracerebral hemorrhage.

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.

• 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.)

Chemical References

• Macrophage Migration-Inhibitory Factors
• Peptide Fragments
• Reactive Oxygen Species
• Collagenases
• Tuftsin

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)