Glutamate release is involved in C. Perfringens epsilon toxin neuropathology

MORRIS WINSTON; GOLDSTEIN JORGE; CANGELOSI ADRIANA; GEOGHEGAN PATRICIA; LOIDL FABIAN; JACOBSEN MARIANA; FERNANDEZ-MIYAKAWA MARIANO

Huerta Grande

Congreso; Second Joint Meeting of the Argentine Society for Neuroscience (SAN: XXV Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias) and the Argentine Workshop in Neuroscience (TAN: XII Taller Argentino de Neurociencias); 2010

Sociedad Argentina de Investigación en Neurociencias

Clostridium perfringens type D epsilon toxin (ETX) affects different animal species and is considered a category B toxin by the Centre of Disease Control, for its potential role in bioterrorism. It affects the vasculature of the brain causing oedema and death. Some reports indicated that excessive neurotransmitter release is also implicated in its pathology. Mice were inoculated intraperitoneally with several different neuroprotective drugs including Riluzole, an inhibitor of glutamate release, and then challenged with ETX (2 LD50). In addition, SD rats were injected via the right lateral ventricle, with either ETX (0.05 LD50) or vehicle. The brains of the mice were removed and processed by histology, stained with H&E and Fluorojade-B. Rat brains were perfusion-fixed either with 2% glutaraldehyde and analyzed by transmission electron microscopy (TEM) or formalin 10% for LM. Toxin-inoculated mice –but no control mice- exhibited convulsive episodes and death, 5 to 30 minutes after ETX inoculation. When treated with Riluzole, mice survived 2 or 3 times longer, and some lived until the termination of the experiment. Both H&E and Fluorojade-B stains revealed neurodegenerative changes in ETX but not in the controls. In the rats, increased amount of neurofilaments in the neuropile and glial processes between pre- and post-synapses were seen with TEM at the cortex, thalamus and striatum. These results suggest that ETX induces significant neurodegenerative changes through excessive glutamate release that may lead to death independently of the vascular damage.