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OBJECTIVE We have previously shown that traumatic injury of hippocampal cells triggers release of a soluble neurotoxin that can be transferred to an uninjured culture. The mechanism of this trauma-induced neurotoxicity is independent of glutamate receptor activation. We extended this observation to study the mechanism of this neurotoxicity. METHODS Dissociated rat hippocampal neurons were traumatized by disrupting the culture by scratching the plate. The toxicity expressed by the injured culture was studied by transferring the medium to an uninjured culture and assessing the death rate by trypan blue exclusion. RESULTS This neurotoxin is stable in the medium at room temperature for several hours and withstands boiling. The molecular weight is between 100 and 500. The release and the effect of this toxin seem to be independent of glutamate receptor activation. The toxicity is unaffected by removal of extracellular calcium. However, dantrolene dose-dependently blocked the toxicity in the recipient culture, suggesting that the release of intracellular stores of calcium is involved in the toxic effect. This release of calcium is likely to be followed by an activation of nitric oxide synthase because competitive nitric oxide synthase inhibitors attenuated this toxicity. Consistent with this result, cholecystokinin octapeptide significantly reduced cell death when combined with this toxic medium. CONCLUSIONS Traumatic injury of dissociated cells can propagate neurotoxicity in uninjured cells by a soluble toxin released into the extracellular space. This toxin causes a rise in cytosolic calcium that activates nitric oxide synthase that can be blocked by cholecystokinin.
K W Yoon, and
H L Mitchell, and
L D Broder, and
R W Brooker, and
R K Delisle
August 1999,
Sheng li xue bao : [Acta physiologica Sinica],
K W Yoon, and
H L Mitchell, and
L D Broder, and
R W Brooker, and
R K Delisle
March 2016,
Alcohol and alcoholism (Oxford, Oxfordshire),
K W Yoon, and
H L Mitchell, and
L D Broder, and
R W Brooker, and
R K Delisle
April 2012,
Arzneimittel-Forschung,
K W Yoon, and
H L Mitchell, and
L D Broder, and
R W Brooker, and
R K Delisle
October 2019,
The International journal of neuroscience,
K W Yoon, and
H L Mitchell, and
L D Broder, and
R W Brooker, and
R K Delisle
May 2008,
Neurochemistry international,
K W Yoon, and
H L Mitchell, and
L D Broder, and
R W Brooker, and
R K Delisle
May 1998,
The European journal of neuroscience,
K W Yoon, and
H L Mitchell, and
L D Broder, and
R W Brooker, and
R K Delisle
November 1998,
Naunyn-Schmiedeberg's archives of pharmacology,
K W Yoon, and
H L Mitchell, and
L D Broder, and
R W Brooker, and
R K Delisle
May 1992,
The Journal of neuroscience : the official journal of the Society for Neuroscience,
K W Yoon, and
H L Mitchell, and
L D Broder, and
R W Brooker, and
R K Delisle
October 2003,
Neuroscience letters,
K W Yoon, and
H L Mitchell, and
L D Broder, and
R W Brooker, and
R K Delisle
October 2008,
Neuroscience letters,
