Chronic daily cortical spreading depressions suppress spreading depression susceptibility.
BACKGROUND
Migraine is a disabling chronic episodic disorder. Attack frequency progressively increases in some patients. Incremental cortical excitability has been implicated as a mechanism underlying progression. Cortical spreading depression (CSD) is the electrophysiological event underlying migraine aura, and a headache trigger. We hypothesized that CSD events during frequent migraine attacks condition the cortex to increase the susceptibility to further attacks.


METHODS
A single daily CSD was induced for 1 or 2 weeks in mouse frontal cortex; contralateral hemisphere served as sham control. At the end of CSD conditioning, occipital CSD susceptibility was determined by measuring the frequency of CSDs evoked by topical KCl application.


RESULTS
Sham hemispheres developed 8.4 ± 0.3 CSDs/hour, and did not significantly differ from naïve controls without prior cranial surgery (9.3 ± 0.4 CSDs/hour). After 2 but not 1 week of daily CSD conditioning, CSD frequency (4.9 ± 0.3 CSDs/hour) as well as the duration and propagation speed were reduced significantly in the conditioned hemispheres. Histopathological examination revealed marked reactive astrocytosis without neuronal injury throughout the conditioned cortex after 2 weeks, temporally associated with CSD susceptibility.


CONCLUSIONS
These data do not support the hypothesis that frequent migraine attacks predispose the brain to further attacks by enhancing tissue susceptibility to CSD.
Harvard Medical School, USA.
Inna
I
Sukhotinsky
Ergin
E
Dilekoz
Yumei
Y
Wang
Tao
T
Qin
Katharina
K
Eikermann-Haerter
Christian
C
Waeber
Cenk
C
Ayata
D000818:Animals; D001921:Brain / Q000503:physiopathology*; D013181:Cortical Spreading Depression / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020325:Migraine with Aura / Q000139:chemically induced / Q000503:physiopathology*; D011189:Potassium Chloride / Q000633:toxicity
D011189:Potassium Chloride