Overexpressing Glyoxalase 1 Attenuates Acute Hyperglycemia-Exacerbated Neurological Deficits of Ischemic Stroke in Mice

This study investigated the therapeutic effects of the overexpression of glyoxalase 1 (GLO1), a detoxifying enzyme of glycotoxins, on acute hyperglycemia-aggravated ischemic brain injury. In present study, AAV-mediated GLO1 overexpression reduced infarct volume and edema level but did not improve neurofunctional recovery in the mice with MCAO. AAV-GLO1 infection significantly enhanced neurofunctional recovery in the MCAO mice with acute hyperglycemia but not in the mice with normoglycemia. MG-modified proteins expression significantly increased in the ipsilateral cortex of the MCAO mice with acute hyperglycemia. AAV-GLO1 infection attenuated the induction of MG-modified proteins, ER stress formation, and caspase3/7 activation in MG-treated Neuro-2A cells, and reductions in synaptic plasticity and microglial activation were mitigated in the injured cortex of the MCAO mice with acute hyperglycemia. Treatment with ketotifen, a potent GLO1 stimulator, after surgery alleviated neurofunctional deficits and ischemic brain damage in the MCAO mice with acute hyperglycemia. Altogether, our data substantiate that, in ischemic brain injury, GLO1 overexpression can alleviate pathological alterations caused by acute hyperglycemia. Upregulation of GLO1 may be a therapeutic strategy for alleviating SIH-aggravated poor functional outcomes in patients with AIS.PMID:37419278 | DOI:10.1016/j.trsl.2023.07.002
Source: Translational Research : the journal of laboratory and clinical medicine - Category: Laboratory Medicine Authors: Source Type: research