Structural and Functional Effects of C5aR1 Antagonism in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy.

Introduction: The complement response activates upon reperfusion in neonatal hypoxic-ischemic encephalopathy (HIE) and contributes to excessive neuroinflammation and worse outcomes. C5a is a powerful anaphylatoxin central to each of the complement pathways, and its engagement with C5aR1 is directly tied to brain injury and neuronal death. Reasoning C5aR1 antagonism can decrease excessive neuroinflammation and thereby improve neurological and functional outcomes, we tested this hypothesis in a rat model of HIE with PMX205, a small molecule that inhibits C5a-C5aR1 interaction.

Therapeutic hypothermia demonstrates sex-dependent improvements in motor function in a rat model of neonatal hypoxic ischemic encephalopathy.

Neonatal hypoxic ischemic encephalopathy (HIE) is a neurological disease caused by restricted oxygen and blood flow to the brain at or around the time of birth. Long term cognitive and motor sequelae are common and demonstrate sexual dimorphism in animal studies. Therapeutic hypothermia (TH) is the standard of care for HIE, but provides incomplete neuroprotection.

Holin-Dependent Secretion of the Large Clostridial Toxin TpeL by Clostridium perfringens.

Large clostridial toxins (LCTs) are secreted virulence factors found in several species, including , , , and LCTs are large toxins that lack a secretion signal sequence, and studies by others have shown that the LCTs of , TcdA and TcdB, require a holin-like protein, TcdE, for secretion. The TcdE gene is located on the pathogenicity locus (PaLoc) of , and holin-encoding genes are also present in the LCT-encoded PaLocs from and However, the holin (TpeE) associated with the LCT TpeL has no homology and a different membrane topology than TcdE. In addition, TpeE has a membrane topology identical to that of the TatA protein, which is the core of the twin-arginine translocation (Tat) secretion system.