Intracellular calcium toxicity remains the central feature in the pathophysiology of ischaemic cell death in brain. Glutamate-gated channels have been thought to be the major sites of ischaemia-induced toxic calcium entry, but the failure of glutamate antagonists in clinical trials has suggested that glutamate-independent mechanisms of calcium entry during ischaemia must exist and may prove central to ischaemic injury. We have shown that ASICs (acid-sensing ion channels) in brain are glutamate-independent vehicles of calcium flux and transport calcium in greater measure in the setting of the two major neurochemical components of ischaemia: acidosis and substrate depletion. Pharmacological blockade of ASICs markedly attenuates stroke injury with a robust therapeutic time window of 5 h following stroke onset. Here, we describe this new mechanism of calcium toxicity in brain ischaemia and offer a potential new therapy for stroke.
Skip Nav Destination
Article navigation
December 2006
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Conference Article|
October 25 2006
Acidotoxicity in brain ischaemia
R. Simon;
R. Simon
1
1Legacy Clinical Research and Technology Center, 1225 NE 2nd Avenue, Portland, OR 97232, U.S.A.
1To whom correspondence should be addressed (email rsimon@downeurobiology.org).
Search for other works by this author on:
Z. Xiong
Z. Xiong
1Legacy Clinical Research and Technology Center, 1225 NE 2nd Avenue, Portland, OR 97232, U.S.A.
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
June 26 2006
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2006 The Biochemical Society
2006
Biochem Soc Trans (2006) 34 (6): 1356–1361.
Article history
Received:
June 26 2006
Citation
R. Simon, Z. Xiong; Acidotoxicity in brain ischaemia. Biochem Soc Trans 1 December 2006; 34 (6): 1356–1361. doi: https://doi.org/10.1042/BST0341356
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.