Furthermore, if this hypothesis is valid, BBB damage in the peri-ischemic brain may serve as a biomarker for predicting the efficacy of delayed treatment. The benefit of 24 h stimulation protocol is consistent with a recent study showing ameliorate MRI tissue characteristics in the rat MCAO model even when SPG has been started 18 h postocclusion. Treatment efficacy is emphasized in our study by the complete normalization of brain activity and the observed reduction of lesion size. Normalization of hyper-excitability in the peri-ischemic brain might be related to amelioration of blood flow and/or vessels’ integrity. While behavioral studies are awaited to confirm the functional and anatomical study performed here, the clinical implications of our results are emphasized by recent recordings in human patients following stroke or sub-arachnoid hemorrhage showing high frequency of seizures and spreading depolarizations within the peri-lesional brain and their potential role in delayed damage. Together, these findings stress the potential of brain activity monitoring in stroke for diagnosis and treatment decisions and suggest a longer therapeutic window in selected patients. In conclusion, this study shows that SPG-stimulation in rats, even 24 h after the induction of photothrombosis, improves cortical functions and reduces the extent of early BBB dysfunction as well as the size of the necrotic region. These results further strengthen the prevailing notion that SPG therapy may have a beneficial role in the treatment of stroke and emphasize potential mechanisms underlying the effects of SPG stimulation on periischemic brain areas. Endothelial cells play a crucial role in the pathogenesis of many types of human infections. For example, after a microbial pathogen enters the CUDC-907 circulation, it must adhere to and invade the endothelial cell lining of the blood vessels to infect deeper tissues to cause organ dissemination. In addition, by expressing proinflammatory cytokines and leukocyte adhesion molecules, endothelial cells recruit phagocytes to foci of infection and are therefore essential for orchestrating the host defense against microbial pathogens. Because of the importance of endothelial cells in the pathogenesis of bloodstream infections, numerous investigators have used in vitro models of microbial-endothelial cell interactions to study the mechanisms by which distinct microbial pathogens adhere to, invade, damage, and activate endothelial cells. Many of these investigations have used human umbilical vein endothelial cells. For example, mutants of Candida albicans with reduced capacity to damage HUVECs in vitro are likely to have attenuated virulence in a murine model of hematogenously disseminated candidiasis. Also, the capacity of clinical isolates of Staphylococcus aureus to damage HUVECs is directly correlated with their virulence in the rabbit model of infective endocarditis, and inversely correlated with their response to vancomycin in this animal model.