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Intrastriatal Injection of Autologous Blood or Clostridial Collagenase as Murine Models of Intracerebral Hemorrhage
Published on: July 3, 2014
Targeting Macrophage Migration Inhibitory Factor Ameliorates Brain Injury After Intracerebral Hemorrhage in Male Mice
Kang Peng1,2, Hongwei Liu2,3, Wei Zhang2,3
1Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Abstract:
Macrophage migration inhibitory factor (MIF) has been reported as a detrimental factor in ischemic stroke in male animals. MIF concentration is increased in the cerebrospinal fluid and serum in hemorrhagic stroke patients. However, the roles of MIF in intracerebral hemorrhage (ICH) are still uncertain. This study examined the specific mechanisms of MIF in brain injury following ICH in mice. Firstly, adult male C57BL/6J mice received an intracaudate injection of autologous arterial blood or saline solution. Perihematomal tissues were harvested to measure MIF levels. Secondly, mice received an intracaudate injection of recombinant mouse MIF (rMIF) or saline. Thirdly, mice were treated with ISO-1 or vehicle after modeling. MRI scans and behavioral tests were conducted in all parts. All mice were euthanized post-MRI scans, and the harvested brain tissues were utilized for immunochemistry or western blot analysis. We observed that hematolysis occurred at day 1 after ICH initially, and increased from day 3 to day 7 in mice. The level of MIF protein was elevated in the perihematomal tissues at the early stage of ICH. Intracerebral injection of rMIF caused brain edema, microglial activation, and neurological dysfunction in male mice. Furthermore, ISO-1 treatment mitigated brain edema, neuronal apoptosis, neuroinflammation, and neurological deficits at day 3 post-ICH in these mice. The level of MIF protein is elevated following ICH and contributes to secondary brain damage following ICH. Targeting MIF could serve as a potential personalized treatment strategy for ICH.
Insights
Macrophage migration inhibitory factor (MIF) exacerbates brain damage after intracerebral hemorrhage (ICH) in mice. Inhibiting MIF shows potential for treating ICH by reducing brain injury and improving neurological function.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Macrophage migration inhibitory factor (MIF) is implicated in ischemic stroke.
- Elevated MIF levels are observed in cerebrospinal fluid and serum of hemorrhagic stroke patients.
- The specific role of MIF in intracerebral hemorrhage (ICH) brain injury remains unclear.
Purpose of the Study:
- To investigate the mechanisms of MIF in brain injury following ICH in mice.
- To determine if MIF contributes to secondary brain damage after ICH.
- To evaluate the therapeutic potential of targeting MIF in ICH.
Main Methods:
- Intracerebral hemorrhage (ICH) model in male C57BL/6J mice using autologous arterial blood injection.
- Measurement of MIF protein levels in perihematomal tissues.
- Intracerebral administration of recombinant mouse MIF (rMIF) or saline.
- Treatment with ISO-1 (MIF inhibitor) or vehicle.
- Assessment of brain edema, microglial activation, neuronal apoptosis, neuroinflammation, and neurological deficits using MRI, behavioral tests, immunohistochemistry, and western blot.
Main Results:
- MIF protein levels increased in perihematomal tissues during the early stages of ICH.
- Intracerebral injection of rMIF induced brain edema, microglial activation, and neurological dysfunction.
- ISO-1 treatment significantly reduced brain edema, neuronal apoptosis, neuroinflammation, and neurological deficits at day 3 post-ICH.
- Hematolysis was observed from day 1, increasing by day 7 post-ICH.
Conclusions:
- Elevated MIF levels following ICH contribute to secondary brain damage.
- Targeting MIF presents a potential personalized treatment strategy for intracerebral hemorrhage.
- Further research into MIF inhibition could offer new therapeutic avenues for ICH patients.
