Table 1.
Summary of studies on the role of TRPM2 in aggregating ischemic brain/neuron injury.
| Species | Model (s) | Target (s) | Mechanism (s) |
|---|---|---|---|
| Rat | In vitro H2O2 treatment | Neuron | Knockdown of TRPM2 using siRNA inhibited H2O2−induced neuronal death [181]. |
| Mouse | In vitro OGD In vivo tMCAO |
Neuron | Knockdown of TRPM2 using shRNA inhibited OGD-induced neuronal death, and reduced infarction size after MCAO [185]. |
| Mouse | In vitro OGD In vivo BCCAO |
Neuron | Global knockout of TRPM2 inhibited increase of intracellular Zn2+ and ROS production, and attenuated neuronal death after global ischemia [56]. |
| Mouse | In vitro H2O2 treatment In vivo tMCAO |
Neuron | Global knockout of TRPM2 inhibited increase of neuro-excitability in response to H2O2, and attenuated neuronal death and brain injury after tMCAO by promoting pro-survival signaling while inhibiting pro-apoptotic signaling [192]. |
| Mouse | In vivo neonatal hypoxic ischemic brain injury model | Neuron | Global knockout of TRPM2 attenuated neuronal death and reduced infarct size after hypoxic–ischemic brain injury partially by regulating GSK-3β signaling [184]. |
| Mouse | In vivo CA/CPR | Neuron | Inhibition of TRPM2 using clotrimazole reduced neuronal death in male mice, but not in female mice [193]. |
| Mouse | In vivo tMCAO | Neuron | Inhibition of TRPM2 using a peptide inhibitor reduced infarction size after MCAO [194]. |
| Mouse | In vivo tMCAO | Immune cells | Transplantation of bone marrow from global TRPM2 knockout mice into wild-type mice, or inhibition of TRPM2 using ACA reduced infarction size in wild-type mice after MCAO [55]. |
| Mouse | In vivo BCAS | Microglia | Global knockout of TRPM2 inhibited brain damage and cognitive dysfunction [172]. |
| Human | In vitro BSO treatment | Microglia and astrocytes | Knockdown of TRPM2 using siRNA attenuated the inflammatory responses in human microglia and astrocytes [171]. |
OGD, oxygen–glucose deprivation; BCCAO, bilateral common carotid artery occlusion; tMCAO, transient middle cerebral artery occlusion; CA/CPR, cardiac arrest and cardiopulmonary resuscitation; BCAS, bilateral common carotid artery stenosis; BSO, D,L-buthionine-S,R-sulfoximine.