Critical role for Annexin A7 in secondary brain injury mediated by its phosphorylation after experimental intracerebral hemorrhage in rats

Neurobiol Dis. 2018 Feb;110:82-92. doi: 10.1016/j.nbd.2017.11.012. Epub 2017 Dec 2.


Glutamate excitotoxicity has been implicated in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI). Synaptosome associated protein 23 (SNAP23) and SNAP25 are respectively participate in presynaptic glutamate release and postsynaptic glutamate receptor (NMDA receptor) trafficking, both of which are essential for glutamate-mediated excitatory toxicity. SNAP23 and SNAP25 exhibit high homology and SNAP23 has been shown to interact with Annexin A7 (ANXA7). This study was to examine the role of ANXA7 in ICH-induced neuronal damage. A collagenase ICH model was performed in adult male Sprague Dawley rats. First, a possible relationship between ANXA7 and ICH pathology was confirmed by an increase in the protein and mRNA level of ANXA7 in the brain tissue around hematoma of ICH rats and the rescue effects of ANXA7 knockdown in vivo on neuronal death, blood-brain barrier damage, brain edema, neurobehavioral deficient, and inflammatory response. In addition, the rescue effect of ANXA7 knockdown on neurobehavioral deficient was also verified in rat autologous blood injection ICH model. Second, we found that ICH significantly increased the phosphorylation ratio of ANXA7 at the threonine residues mainly in neurons. Finally, based on site-specific mutagenesis, we identified that ANXA7 phosphorylation at threonine 286 is required for its interaction with SNAP25 at presynaptic axon terminal and SNAP23 at postsynaptic axon terminal. Collectively, our findings suggest that ANXA7 contributed to SBI at least partially through regulating glutamate toxicity after ICH. Selective inhibition of ANXA7 phosphorylation may be a novel approach to ameliorate ICH-induced SBI.

Keywords: Annexin A7; Glutamate toxicity; Intracerebral hemorrhage; Phosphorylation; Secondary brain injury; Synaptosome associated protein 23; Synaptosome associated protein 25.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A7 / metabolism*
  • Brain Injuries / etiology
  • Brain Injuries / metabolism
  • Brain Injuries / pathology
  • Cerebral Hemorrhage / complications
  • Cerebral Hemorrhage / metabolism*
  • Cerebral Hemorrhage / pathology*
  • Disease Models, Animal
  • Male
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley


  • Annexin A7