Chronically epileptic human and rat neocortex display a similar resistance against spreading depolarization in vitro
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Chronically epileptic human and rat neocortex display a similar resistance against spreading depolarization in vitro. / Maslarova, Anna; Alam, Mesbah; Reiffurth, Clemens; Lapilover, Ezequiel; Gorji, Ali; Dreier, Jens P.
In: STROKE, Vol. 42, No. 10, 10.2011, p. 2917-22.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Chronically epileptic human and rat neocortex display a similar resistance against spreading depolarization in vitro
AU - Maslarova, Anna
AU - Alam, Mesbah
AU - Reiffurth, Clemens
AU - Lapilover, Ezequiel
AU - Gorji, Ali
AU - Dreier, Jens P
PY - 2011/10
Y1 - 2011/10
N2 - BACKGROUND AND PURPOSE: Experimental and clinical evidence suggests that prolonged spreading depolarizations (SDs) are a promising target for therapeutic intervention in stroke because they recruit tissue at risk into necrosis by protracted intracellular calcium surge and massive glutamate release. Unfortunately, unlike SDs in healthy tissue, they are resistant to drugs such as N-methyl-d-aspartate-receptor antagonists. This drug resistance of SD in low perfusion areas may be due to the gradual rise of extracellular potassium before SD onset. Brain slices from patients undergoing surgery for intractable epilepsy allow for screening of drugs, targeting pharmacoresistant SDs under elevated potassium in human tissue. However, network changes associated with epilepsy may interfere with tissue susceptibility to SD. This could distort the results of pharmacological tests.METHODS: We investigated the threshold for SD, induced by a gradual rise of potassium, in neocortex slices of patients with intractable epilepsy and of chronically epileptic rats as well as age-matched and younger control rats using combined extracellular potassium/field recordings and intrinsic optical imaging.RESULTS: Both age and epilepsy significantly increased the potassium threshold, which was similarly high in epileptic rat and human slices (23.6±2.4 mmol/L versus 22.3±2.8 mmol/L).CONCLUSIONS: Our results suggest that chronic epilepsy confers resistance against SD. This should be considered when human tissue is used for screening of neuroprotective drugs. The finding of similar potassium thresholds for SD in epileptic human and rat neocortex challenges previous speculations that the resistance of the human brain against SD is markedly higher than that of the rodent brain.
AB - BACKGROUND AND PURPOSE: Experimental and clinical evidence suggests that prolonged spreading depolarizations (SDs) are a promising target for therapeutic intervention in stroke because they recruit tissue at risk into necrosis by protracted intracellular calcium surge and massive glutamate release. Unfortunately, unlike SDs in healthy tissue, they are resistant to drugs such as N-methyl-d-aspartate-receptor antagonists. This drug resistance of SD in low perfusion areas may be due to the gradual rise of extracellular potassium before SD onset. Brain slices from patients undergoing surgery for intractable epilepsy allow for screening of drugs, targeting pharmacoresistant SDs under elevated potassium in human tissue. However, network changes associated with epilepsy may interfere with tissue susceptibility to SD. This could distort the results of pharmacological tests.METHODS: We investigated the threshold for SD, induced by a gradual rise of potassium, in neocortex slices of patients with intractable epilepsy and of chronically epileptic rats as well as age-matched and younger control rats using combined extracellular potassium/field recordings and intrinsic optical imaging.RESULTS: Both age and epilepsy significantly increased the potassium threshold, which was similarly high in epileptic rat and human slices (23.6±2.4 mmol/L versus 22.3±2.8 mmol/L).CONCLUSIONS: Our results suggest that chronic epilepsy confers resistance against SD. This should be considered when human tissue is used for screening of neuroprotective drugs. The finding of similar potassium thresholds for SD in epileptic human and rat neocortex challenges previous speculations that the resistance of the human brain against SD is markedly higher than that of the rodent brain.
KW - Animals
KW - Cortical Spreading Depression
KW - Epilepsy
KW - Humans
KW - Male
KW - Neocortex
KW - Pilocarpine
KW - Rats
KW - Rats, Wistar
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1161/STROKEAHA.111.621581
DO - 10.1161/STROKEAHA.111.621581
M3 - SCORING: Journal article
C2 - 21836085
VL - 42
SP - 2917
EP - 2922
JO - STROKE
JF - STROKE
SN - 0039-2499
IS - 10
ER -