Endovascular Stem Cell Therapy Promotes Neuronal Remodeling to Enhance Post Stroke Recovery by Alleviating Endoplasmic Reticulum Stress Modulated by BDNF Signaling

Hypoxia and its effect on the cellular system

“… Longxuetongluo Capsule has been reported to be neuroprotective via alleviation of ER stress in in vitro and in vivo model of cerebral ischemia 126 Phenothiazines (chlorpromazine+promethazine combination) can reduce ER stress and results neuroprotection in male SD rats that has undergone 2 h of MCAo surgery 127 Acupuncture treatment in Baihui (GV20), and Qubin (GB7) accupoints are reported to offer neuroprotection against ischemic reperfusion injury by modulating ER stress mediated autophagy and apoptosis 128 Bone marrow derived allogenic mesenchymal stem cells are reported neuroprotective via reducing ER stress mediated apoptosis by modulating BDNF/TrkB pathway, and promotes neuronal remodeling in rodent model of ischemic stroke as well as OGD mediated hypoxic cellular model in vitro 129–131 Mild and heavy exercise postconditioning in a rodent model of ischemic stroke are neuroprotective via regulating SIRT‐1 mediated ER stress pathway 132 Astragalin, the flavonoid is reported to alleviate ER stress and decrease apoptotic protein expression in a transient middle cerebral artery occlusion (tMCAo) model of rodent stroke to render neuroprotection 133 Hes1 knockdown, following activation of PERK UPR pathway worsened stroke prognosis, increased cerebral infarction, and enhanced ER stress mediated apoptosis in an in vivo tMCAo model of stroke 134 Decreased expression of p‐eIF2α and p‐PERK by PERK knock out using crossbreed Camk2a‐CreERT2 with Perkf/fmice decreased neuroscore and increased infarct volume in the mice 135 ATF4 overexpression induced by Adeno‐associated virus in an MCAo model of stroke resulted neuroprotection 136 Subcutaneus administration of G‐CSF (50 μg/kg) for 4 days reduced neuronal degeneration and increased long‐term neuronal plasticity following global cerebral ischemia 137 ATF4 silencing in a tMCAo model of stroke decreases cerebral infarct 138 Fourteen days administration of chrysophanol (0.1 mg/kg) decreased ER stress response and reduced neuronal apoptosis in an MCAo model of stroke 139 Reduction in the expression of CHOP and Ero1‐α by hypothermia (31°C) reduced ER stress related apoptosis in in vivo stroke model 140 Increased expression of GADD34 and p‐eIF2α by salubrinal renders neuroprotection via reducing CA1 cell death and BBB disruption following MCAo induced stroke 141,142 Intervening the IRE1 pathway by increasing XBP1 expression, and decreasing the phosphorylation of IRE1a in an in vitro OGD/R model of primary rat hippocampal neuron culture and primary microglial and cortical neurons decreased cell death 143 5 mg/kg melatonin at the initiation of reperfusion in an MCAo model of stroke, suppresses PERK signaling pathway and decreases infarct volume 144 Melatonin pretreatment can relive cerebral edema and neuronal damage in tMCAo model of stroke via reducing p‐PERK and p‐IRE1 protein expressions 145 Pharmacological activation of ATF6 can ...…”

“…Bone marrow derived allogenic mesenchymal stem cells are reported neuroprotective via reducing ER stress mediated apoptosis by modulating BDNF/TrkB pathway, and promotes neuronal remodeling in rodent model of ischemic stroke as well as OGD mediated hypoxic cellular model in vitro 129–131 …”

Mesenchymal stem cell engineering by ARCA analog-capped mRNA

“…Mesenchymal stem cells (MSCs) are known for their universally supportive role and participation in reparative processes; thus, they are well suited for regenerative medicine. 1 , 2 , 3 …”