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Formation of complement membrane attack complex in mammalian cerebral cortex evokes seizures and neurodegeneration.

Publication ,  Journal Article
Xiong, Z-Q; Qian, W; Suzuki, K; McNamara, JO
Published in: J Neurosci
February 1, 2003

The complement system consists of >30 proteins that interact in a carefully regulated manner to destroy invading bacteria and prevent the deposition of immune complexes in normal tissue. This complex system can be activated by diverse mechanisms proceeding through distinct pathways, yet all converge on a final common pathway in which five proteins assemble into a multimolecular complex, the membrane attack complex (MAC). The MAC inserts into cell membranes to form a functional pore, resulting in ion flux and ultimately osmotic lysis. Immunohistochemical evidence of the MAC decorating neurons in cortical gray matter has been identified in multiple CNS diseases, yet the deleterious consequences, if any, of MAC deposition in the cortex of mammalian brain in vivo are unknown. Here we demonstrate that the sequential infusion of individual proteins of the membrane attack pathway (C5b6, C7, C8, and C9) into the hippocampus of awake, freely moving rats induced both behavioral and electrographic seizures as well as cytotoxicity. The onset of seizures occurred during or shortly after the infusion of C8/C9. Neither seizures nor cytotoxicity resulted from the simultaneous infusion of all five proteins premixed in vitro. The requirement for the sequential infusion of all five proteins together with the temporal relationship of seizure onset to infusions of C8/C9 implies that the MAC was formed in vivo and triggered both seizures and cytotoxicity. Deposition of the complement MAC in cortical gray matter may contribute to epileptic seizures and cell death in diverse diseases of the human brain.

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Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

February 1, 2003

Volume

23

Issue

3

Start / End Page

955 / 960

Location

United States

Related Subject Headings

  • Wakefulness
  • Seizures
  • Rats, Sprague-Dawley
  • Rats
  • Neurons
  • Neurology & Neurosurgery
  • Neurodegenerative Diseases
  • Male
  • Immunohistochemistry
  • Hippocampus
 

Citation

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Xiong, Z.-Q., Qian, W., Suzuki, K., & McNamara, J. O. (2003). Formation of complement membrane attack complex in mammalian cerebral cortex evokes seizures and neurodegeneration. J Neurosci, 23(3), 955–960. https://doi.org/10.1523/JNEUROSCI.23-03-00955.2003
Xiong, Zhi-Qi, Weihua Qian, Katsuaki Suzuki, and James O. McNamara. “Formation of complement membrane attack complex in mammalian cerebral cortex evokes seizures and neurodegeneration.J Neurosci 23, no. 3 (February 1, 2003): 955–60. https://doi.org/10.1523/JNEUROSCI.23-03-00955.2003.
Xiong Z-Q, Qian W, Suzuki K, McNamara JO. Formation of complement membrane attack complex in mammalian cerebral cortex evokes seizures and neurodegeneration. J Neurosci. 2003 Feb 1;23(3):955–60.
Xiong, Zhi-Qi, et al. “Formation of complement membrane attack complex in mammalian cerebral cortex evokes seizures and neurodegeneration.J Neurosci, vol. 23, no. 3, Feb. 2003, pp. 955–60. Pubmed, doi:10.1523/JNEUROSCI.23-03-00955.2003.
Xiong Z-Q, Qian W, Suzuki K, McNamara JO. Formation of complement membrane attack complex in mammalian cerebral cortex evokes seizures and neurodegeneration. J Neurosci. 2003 Feb 1;23(3):955–960.

Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

February 1, 2003

Volume

23

Issue

3

Start / End Page

955 / 960

Location

United States

Related Subject Headings

  • Wakefulness
  • Seizures
  • Rats, Sprague-Dawley
  • Rats
  • Neurons
  • Neurology & Neurosurgery
  • Neurodegenerative Diseases
  • Male
  • Immunohistochemistry
  • Hippocampus