Longitudinal MRI evaluation of neuroprotective effects of pharmacologically induced hypothermia in experimental ischemic stroke

Abstract

Pharmacologically induced hypothermia (PIH) shows promising neuroprotective effects after stroke insult. However, the dynamic evolution of stroke infarct during the hypothermic therapy has not been understood very well. In the present study, MRI was utilized to longitudinally characterize the infarct evolution in a mouse model of ischemic stroke treated by PIH using the neurotensin agonist HPI201. Adult male C57BL/6 mice underwent permanent occlusion of the right middle cerebra artery (MCA). Each animal received a vehicle or HPI201 intraperitoneal injection. The temporal changes of stroke lesion were examined using T2-weighted imaging and diffusion-weighted imaging (DWI) in the acute phase (1–3 hours) and 24 hours post stroke. Significantly reduced infarct and edema volumes were observed in PIH treated stroke mice, in agreement with TTC staining findings. Also, the TUNEL staining results indicated apoptotic cells were widely distributed among the ischemic cortex in control group but limited in PIH treated mice. Dramatically reduced growth rate of infarction was seen in PIH treated stroke mice. These results demonstrate HPI201 has strong neuroprotection effects during acute stroke. In particular, MRI with the numerical modelling of temporal infarct evolution could provide a unique means to examine and predict the dynamic response of the PIH treatment on infarct evolution.

Transient selective brain cooling confers neurovascular and functional protection from acute to chronic stages of ischemia/reperfusion brain injury

“…cascade that is set in motion in the acute to subacute stages of ischemic injury, encompassing early BBB disruption and subsequent immune cell infiltration and propagation of inflammation. 23,24 In most stroke studies, BBB damage is typically measured 24 h after ischemia. 24 However, Shi et al 13 demonstrated early BBB disruption during the acute stage (<3 h) after stroke, followed by secondary irreversible BBB disruption.…”

“…23,24 In most stroke studies, BBB damage is typically measured 24 h after ischemia. 24 However, Shi et al 13 demonstrated early BBB disruption during the acute stage (<3 h) after stroke, followed by secondary irreversible BBB disruption. As argued above, the acute stage of BBB disruption affects long-term outcomes by facilitating immune cell infiltration and subsequent neuroinflammatory processes.…”

“…As argued above, the acute stage of BBB disruption affects long-term outcomes by facilitating immune cell infiltration and subsequent neuroinflammatory processes. [23][24][25] Therefore, we evaluated BBB leakage from 1 to 23 h after reperfusion in our experiments. As expected, TSBH conferred dramatic protection against BBB breakdown from 1 to 23 h post-reperfusion onset.…”

“…Therefore, TSBH treatment may interrupt a self-amplifying ischemic cascade that is set in motion in the acute to subacute stages of ischemic injury, encompassing early BBB disruption and subsequent immune cell infiltration and propagation of inflammation. 23,24…”

Leptomeningeal anastomosis and early ischemic lesions on diffusion‐weighted imaging in male murine focal cerebral ischemia

“…Early ischemic lesions are routinely evaluated on MRI-DWI in stroke medicine, and the size of the ischemic lesion has been shown to be associated with the degree of collateral circulation (Aoki et al, 2014;Campbell et al, 2013;Gawlitza et al, 2017;Kim et al, 2014;Lee et al, 2015;Verma et al, 2015), such that poor collateral circulation is closely related to the expansion of early ischemic lesions on MRI-DWI. In the experimental models, MRI has been used to evaluate lesion size and edema volume (Gupta, Sharma, Jagannathan, & Gupta, 2017;He et al, 2017;Huang et al, 2013;Okubo et al, 2007;Woo et al, 2017;Xu et al, 2015;Zhao et al, 2016) as in human stroke, and the beneficial effect of hypothermia on early ischemic lesions has been demonstrated in an MRI-DWI experiment (Wang et al, 2017). However, in experimental ischemia, the in vivo evaluation of leptomeningeal anastomoses throughout the entire hemisphere was technically challenging owing to small brain size; therefore, several groups, including ours, have applied the injection of latex beads (Todo et al, 2008) and contrast medium (Chen et al, 2007).…”