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Stress-induced hyperglycemia (SIH) is associated with poor functional recovery and high mortality in patients with acute ischemic stroke (AIS). However, intensive controlling of blood glucose by using insulin was not beneficial in patients with AIS and acute hyperglycemia. This study investigated the therapeutic effects of the overexpression of glyoxalase I (GLO1), a detoxifying enzyme of glycotoxins, on acute hyperglycemia–aggravated ischemic brain injury. In the present study, adeno-associated viral (AAV)-mediated GLO1 overexpression reduced infarct volume and edema level but did not improve neurofunctional recovery in the mice with middle cerebral artery occlusion (MCAO). AAV-GLO1 infection significantly enhanced neurofunctional recovery in the MCAO mice with acute hyperglycemia but not in the mice with normoglycemia. Methylglyoxal (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 caspase 3/7 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 pathologic alterations caused by acute hyperglycemia. Upregulation of GLO1 may be a therapeutic strategy for alleviating SIH-aggravated poor functional outcomes in patients with AIS. [ABSTRACT FROM AUTHOR]

• We provide a novel animal model of NMO by intrathecal injection of NMO-IgG into EAE mice. • This animal model closely recapitulates human NMO pathology with relevant clinical severity. • The results imply that NMO-IgG is a key role of the immune response and clinical severity of NMO. Neuromyelitis optica (NMO) is recognized as a different CNS autoimmune disease from multiple sclerosis (MS). Whether NMO-IgG contributes directly to the pathogenesis of NMO or is just a serologic marker of autoimmune responses of the disease needs to be clarified. We created MOG-induced experimental autoimmune encephalomyelitis (EAE) mice by passively transferring NMO-IgG to model the pathogenic findings in NMO patients. The mice were divided into three groups and administered intrathecal PBS, human complement with IgG from normal subjects, or IgG from AQP4(+) patients on days 8 and 11 after immunization. The EAE scores of EAE mice with intrathecal NMO-IgG injection were significantly elevated 14 days post-immunization. All of the mice were sacrificed for brain and spinal cord pathology analysis on day 21 post-immunization. Compared to mice given normal human IgG, EAE mice injected with NMO-IgG had markedly decreased AQP4 and glial fibrillary acidic protein (GFAP) expression and fluorescent intensity in the brain and spinal cord but more scattered deposition of complement (C9neo). Thus, our studies not only support the pathogenic role of NMO-IgG with complement in NMO disease but also provide a platform for the development of future therapeutics. [ABSTRACT FROM AUTHOR]