Infarct growth precedes cerebral thrombosis following experimental stroke in mice

Abstract

Ischemic stroke is among the leading causes of disability and death worldwide. In acute ischemic stroke, successful recanalization of occluded vessels is the primary therapeutic aim, but even if it is achieved, not all patients benefit. Although blockade of platelet aggregation did not prevent infarct progression, cerebral thrombosis as cause of secondary infarct growth has remained a matter of debate. As cerebral thrombi are frequently observed after experimental stroke, a thrombus-induced impairment of the brain microcirculation is considered to contribute to tissue damage. Here, we combine the model of transient middle cerebral artery occlusion (tMCAO) with light sheet fluorescence microscopy and immunohistochemistry of brain slices to investigate the kinetics of thrombus formation and infarct progression. Our data reveal that tissue damage already peaks after 8 h of reperfusion following 60 min MCAO, while cerebral thrombi are only observed at later time points. Thus, cerebral thrombosis is not causative for secondary infarct growth during ischemic stroke.

Selenium supplementation provides potent neuroprotection following cerebral ischemia in mice

“…Consistent with published data from both our group and others, we found that the cerebral infarct volume peaked at 24 h post-lesion and then decreased by 72 h. 25,28–30 We found that selenium treatment significantly reduced the volumes of cerebral infarction (Figure 1(b) to (d); 22.41 ± 2.22% vs. 41.55 ± 2.64%; t(26) = 5.572, P < 0.0001) and edema (Figure 1(e); 2.04 ± 0.45% vs. 12.74 ± 1.36%; t(25) = 8.136, P < 0.0001) at the 24 h timepoint compared with the tMCAO group. At 72 h, although the tMCAO mice had reduced lesion size compared to the 24 h timepoint, selenium treatment facilitated the recovery process by further reducing the infarct (Figure 1(c) and (d); 9.17 ± 2.11% vs. 22.06 ± 2.69%; t(21) = 3.725, P = 0.0013) and edema (Figure 1(e); 0.81 ± 0.27% vs. 7.39 ± 0.57%; t(20) = 9.840, P < 0.0001) volumes.…”

“…Consistent with published data from both our group and others, we found that the cerebral infarct volume peaked at 24 h post-lesion and then decreased by 72 h. 25,[28][29][30] We found that selenium treatment significantly reduced the volumes of cerebral infarction (Figure 1 At 24 h, selenium treatment significantly reduced the neurological deficit score of the tMCAO þ Se mice (Figure 1(f); 1.00 AE 0.13 vs. 1.58 AE 0.16; t(26) ¼ 2.962, P ¼ 0.0065). At 72 h, approximately 50% of mice in the tMCAO þ Se group displayed no motor function impairments (neurological deficit score ¼ 0), and the average score was significantly lower than that of the tMCAO group (Figure 1(f); 0.53 AE 0.17 vs. 1.18 AE 0.13; t(29) ¼ 3.074, P ¼ 0.0046), suggesting that recovery from the tMCAO insult was expedited by selenium treatment.…”

Delayed NLRP3 inflammasome inhibition ameliorates subacute stroke progression in mice

“…A recent study describing infarctions to reach their maximum size after 8 h of reperfusion does not contradict our findings, as they followed a 60 min tMCAO protocol resulting in much larger infarct volumes that comprised the whole anterior circulation [32]. Infarctions presented here, however, were much smaller in size (only "subletal") leaving enough brain tissue to be damagedor saved-secondarily.…”

Platelet glycoprotein V spatio-temporally controls fibrin formation

“…The methanol was replaced stepwise by a clearing solution consisting of one part benzyl alcohol to two parts benzyl benzoate (BABB; 305197 and B6630, Sigma-Aldrich). After incubation in the clearing solution for at least 2 h at room temperature, tissue specimens became optically transparent and were used for light sheet fluorescence microscopy (LSFM) imaging on the following day 68 .…”