Cortical spreading depression activates and upregulates MMP-9
J. Clin. Invest. Yasemin Gursoy-Ozdemir, et al. 113:1447 doi:10.1172/JCI21227 [
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Figure 1CSD caused time-dependent increases in MMP-9 levels, as assessed by gelatin gel zymography. Unilateral CSD was elicited by pinprick in the frontal cortex as described (see Methods). (
A) MMP-9 gelatinolytic activity was consistently higher on the CSD side from 6 to 48 hours and returned to basal levels by 96 hours. The molecular weights of both bands corresponded to those of rat MMP-9 (92 kDa and 88 kDa). (
B) Comparison of MMP-9 responses induced by CSD versus MMP-9 in conditioned media from rat cortical neuron (NC) and astrocyte (AC) cell cultures incubated with 100 nM phorbol myristate acetate (PMA) for 24 hours. 92 kDa recombinant human MMP-9 (H) and 105 kDa recombinant mouse MMP-9 (M) standards were also loaded as molecular weight markers. MMP-9 bands induced by CSD at 24 hours matched those obtained from neuron and astrocyte cultures. Ips, ipsilateral (CSD); Cont, contralateral (non-CSD). (
C) Densitometric measurements confirm the increase in MMP-9 induced by CSD. Constitutive MMP-2 expression and activity did not change after CSD and were visualized in sham as well. nCSD, non-CSD. *
P < 0.05 compared with the contralateral side.