Why the study?
Amyloid-beta peptide accumulation and astrocytic pyroptosis exacerbate cerebral ischemia/reperfusion injury and poststroke dementia, but the intervention effects of Tongxinluo on these pathways remained to be explored.
Does Tongxinluo reduce astrocytic pyroptosis and Amyloid-β accumulation in rats with cerebral ischemia/reperfusion injuries?
Does Tongxinluo reduce astrocytic pyroptosis and Amyloid-β accumulation in rats with cerebral ischemia/reperfusion injuries?
Tongxinluo exerts protective effects against ischemic brain injury by inhibiting astrocytic pyroptosis and reducing toxic Aβ accumulation in a rat model of cerebral ischemia/reperfusion.
Should not yet change stroke practice; hypothesis-generating for Tongxinluo in cerebral ischemia models.
Amyloid-β peptide (Aβ) accumulation is a detrimental factor in cerebral ischemia/reperfusion (I/R) injuries accounting for dementia induced by ischemic stroke. In addition to blood brain barrier (BBB), the glymphatic system mediated by aquaporin-4 (AQP-4) on astrocytic endfeet functions as an important pathway for the clearance of Aβ in the brain. Cerebral I/R induced astrocytic pyroptosis potentially causes the AQP-4 polarization loss and dysfunctional BBB-glymphatic system exacerbating the accumulation of Aβ. Furthermore, Aβ toxicity has been identified as a trigger of pyroptosis and BBB damage, suggesting an amplified effect of Aβ accumulation after cerebral I/R. Therefore, based on our previous work, this study was designed to explore the intervention effects of Tongxinluo (TXL) on astrocytic pyroptosis and Aβ accumulation after cerebral I/R in rats. The results showed that TXL intervention obviously alleviated the degree of pyroptosis by downregulating expression levels of cleaved caspase-11/1, N-terminal gasdermin D, nucleotide-binding oligomerization domain-like receptors pyrin domain containing 3 (NLRP3), interleukin-6 (IL-6), and cleaved IL-1β and abated astrocytic pyroptosis after cerebral I/R. Moreover, TXL intervention facilitated to restore AQP-4 polarization and accordingly relieve Aβ accumulation around astrocytes in ischemic cortex and hippocampus as well as the formation of toxic Aβ (Aβ1–42 oligomer). Our study indicated that TXL intervention could exert protective effects on ischemic brain tissues against pyroptotic cell death, inhibit astrocytic pyroptosis, and reduce toxic Aβ accumulation around astrocytes in cerebral I/R injuries. Furthermore, our study provides biological evidence for the potential possibility of preventing and treating poststroke dementia with TXL in clinical practice.
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Wang et al. (2021) studied this question.
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