Synthetic gelatinases inhibitor attenuates electromagnetic pulse-induced blood-brain barrier disruption by inhibiting gelatinases-mediated ZO-1 degradation in rats.

Previously we found that exposure to electromagnetic pulse (EMP) induced an increase in blood-brain-barrier (BBB) permeability and the degradation of tight junction protein ZO-1 in rats. Matrix metalloproteinases (MMPs), in particular gelatinases (MMP-2 and MMP-9), play a key role in degradation of tight junction proteins, are known mediators of BBB compromise. We hypothesized that the degradation of ZO-1 by gelatinases contributed to EMP-induced BBB opening. To test this hypothesis, the mRNA level of ZO-1, protein levels of MMP-2, MMP-9 and tissue inhibitor of metalloproteinases (TIMP-1 and TIMP-2) were detected in rat cerebral cortex after exposing rats to EMP at 200 kV/m for 200 pulses. It was found that the mRNA level of ZO-1 was unaltered at different time points after EMP exposure. The protein levels of MMP-2 and MMP-9 significantly increased at 3 h and 0.5 h, respectively. However, TIMP-1 (inhibitor of MMP-9) and TIMP-2 (inhibitor of MMP-2) only moderately increased after EMP exposure. In addition, in situ zymography results showed that the gelatinase activity increased in cerebral microvessels at 3 h after EMP exposure. When rats were treated with gelatinases inhibitor (SB-3CT) before EMP exposure, the EMP-induced BBB opening was attenuated and the ZO-1 degradation was reversed. Our results suggested that EMP-induced BBB opening was related to gelatinase mediated ZO-1 degradation.

Qiu LB ，Zhou Y ，Wang Q ，Yang LL ，Liu HQ ，Xu SL ，Qi YH ，Ding GR ，Guo GZ ... -  《-》

EMP-induced alterations of tight junction protein expression and disruption of the blood-brain barrier.

The blood-brain barrier (BBB) is critical to maintain cerebral homeostasis. In this study, we examined the effects of exposure to electromagnetic pulse (EMP) on the functional integrity of BBB and, on the localization and expression of tight junction (TJ) proteins (occludin and ZO-1) in rats. Animals were sham or whole-body exposed to EMP at 200 kV/m for 400 pulses. The permeability of BBB in rat cerebral cortex was examined by using Evans Blue (EB) and lanthanum nitrate as vascular tracers. The localization and expression of TJ proteins were assessed by western blot and immunofluorescence analysis, respectively. The data indicated that EMP exposure caused: (i) increased permeability of BBB, and (ii) altered localization as well as decreased levels of TJ protein ZO-1. These results suggested that the alteration of ZO-1 may play an important role in the disruption of tight junctions, which may lead to dysfunction of BBB after EMP exposure.

Ding GR ，Qiu LB ，Wang XW ，Li KC ，Zhou YC ，Zhou Y ，Zhang J ，Zhou JX ，Li YR ，Guo GZ ... -  《-》

Effects of electromagnetic pulse exposure on gelatinase of blood-brain barrier in vitro.

Zhou Y ，Qiu LB ，An GZ ，Zhou JX ，Du L ，Ma YH ，Guo GZ ，Ding GR ... -  《-》

[Effects of electromagnetic pulse on blood-brain barrier permeability and tight junction proteins in rats].

Qiu LB ，Ding GR ，Zhang YM ，Zhou Y ，Wang XW ，Li KC ，Xu SL ，Tan J ，Zhou JX ，Guo GZ ... -  《-》

Matrix metalloproteinases inhibition provides neuroprotection against hypoxia-ischemia in the developing brain.

Chen W ，Hartman R ，Ayer R ，Marcantonio S ，Kamper J ，Tang J ，Zhang JH ... -  《-》