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Complement depletion improves neurological function in cerebral ischemia
U S Vasthare1, F C Barone, H M Sarau
1Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Insights
Depleting the complement system significantly improved blood flow and neurological outcomes in rats after cerebral ischemia and reperfusion injury. This suggests the complement system exacerbates brain damage during these events.
Area of Science:
- Neuroscience
- Immunology
- Cardiovascular Research
Background:
- Cerebral ischemia/reperfusion (I/R) injury is a major cause of brain damage.
- The complement system, a part of innate immunity, is implicated in inflammatory processes and tissue damage.
Purpose of the Study:
- To investigate the role of the complement system in exacerbating cerebral I/R injury.
- To determine if complement depletion improves outcomes following cerebral I/R.
Main Methods:
- Compared rats with normal complement levels to those depleted of complement using cobra venom factor (CVF).
- Assessed reactive hyperemia, somatosensory evoked potentials (SSEPs), and leukocyte infiltration (myeloperoxidase and Leukotriene B4 activity).
Main Results:
- Complement-depleted rats showed significantly greater reactive hyperemia.
- Better preservation of SSEPs was observed in complement-depleted animals.
- No significant differences in leukocyte infiltration were found between groups.
Conclusions:
- Complement system activation contributes to the exacerbation of cerebral I/R injury.
- Complement depletion improves cerebral blood flow and neurological outcomes after I/R.
- The protective effects are independent of changes in leukocyte infiltration.
Abstract:
The contribution of the complement system to the exacerbation of cerebral ischemia/reperfusion injury was studied by comparing a group of rats with normal complement levels to another group that was complement depleted by cobra venom factor (CVF). The magnitude of reactive hyperemia was significantly greater in the complement depleted animals. There was also better preservation of somatosensory evoked potentials (SSEPs) in the complement depleted animals. These differences were not associated with changes in leukocyte infiltration as evidenced by myeloperoxidase and Leukotriene B4 activity. These data demonstrate that depleting the complement system can improve flow and outcome following cerebral ischemia with reperfusion.