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Updated: Jun 16, 2026
05:27
Inner Mitochondrial Membrane Sensitivity to Na+ Reveals Partially Segmented Functional CoQ Pools
Published on: July 20, 2022
Complement component c1q mediates mitochondria-driven oxidative stress in neonatal hypoxic-ischemic brain injury
Vadim S Ten1, Jun Yao, Veniamin Ratner
1Departments of Pediatrics, Neurosurgery, and Physiology and Cellular Biophysics, Columbia University, New York, New York 10032, USA. vt82@columbia.edu
Summary
Complement C1q exacerbates infant hypoxic-ischemic brain injury by increasing oxidative stress. Targeting C1q may offer neuroprotection against this common cause of lifelong disability.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Hypoxic-ischemic (HI) brain injury in infants is a significant cause of lifelong disability.
- Oxidative stress plays a critical role in the pathogenesis of HI brain injury.
- The complement system, particularly C1q, is implicated in inflammatory and immune responses.
Purpose of the Study:
- To investigate the role of the complement component C1q in mediating oxidative brain injury following hypoxia-ischemia.
- To elucidate the specific mechanisms by which C1q contributes to neuronal damage in the developing brain.
- To evaluate the therapeutic potential of targeting C1q for neuroprotection against HI injury.
Main Methods:
- Utilized a neonatal mouse model of hypoxia-ischemia (HI).
- Compared HI outcomes in wild-type, C1q-deficient, and C6-deficient mice, as well as with pharmacologically inhibited membrane attack complex.
- Assessed reactive oxygen species (ROS) production in brain mitochondria and neuronal survival following oxygen-glucose deprivation.
- Investigated the effect of exogenous C1q and antioxidant treatment on neuronal injury.
Main Results:
- C1q-deficient mice exhibited significant neuroprotection and attenuated oxidative brain injury post-HI.
- Mitochondrial ROS production was reduced, and respiratory chain activity was preserved in C1q-deficient brains.
- Cortical neurons from C1q-deficient mice showed resistance to oxygen-glucose deprivation, which was reversed by exogenous C1q.
- Exogenous C1q increased mitochondrial ROS and mortality, effects abolished by the antioxidant Trolox.
Conclusions:
- The C1q component of complement exacerbates oxidative brain injury in the developing HI brain by accelerating mitochondrial ROS emission.
- C1q-mediated mitochondrial oxidative stress is a primary pathogenic mechanism, potentially more significant than terminal complement activation in HI injury.
- Targeting C1q offers a promising therapeutic strategy for mitigating HI neonatal brain injury.
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