Neuronal injury in glaucoma persists despite effective intraocular pressure (IOP) control, necessitating neuroprotective strategies for retinal ganglion cells (RGCs). In this study, we investigated the neuroprotective role of the γ-hydroxybutyrate analog HOCPCA in a glaucoma model, focusing on its effects on CaMKII signaling, oxidative stress, and neuroinflammatory responses. Retinal tissue from high IOP animal models was analyzed via proteomics. In vitro mouse retinal explants were subjected to elevated pressure and oxidative stress, followed by HOCPCA treatment. HOCPCA significantly mitigated the RGC loss induced by oxidative stress and elevated pressure, preserving neuronal function. It restored CaMKIIα and β levels, preserving RGC integrity, while also modulating oxidative stress and neuroinflammatory responses. These findings suggest that HOCPCA, through its interaction with CaMKII, holds promise as a neuroprotective therapy for glaucoma.
Animals ; Retinal Ganglion Cells/metabolism* ; Glaucoma/pathology* ; Oxidative Stress/drug effects* ; Neuroprotective Agents/pharmacology* ; Mice ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism* ; Mice, Inbred C57BL ; Disease Models, Animal ; Neuroinflammatory Diseases/drug therapy* ; Neuroprotection/drug effects* ; Male ; Intraocular Pressure/drug effects*

Objective To determine the occurrence and baseline predictive factors of early neurological deterioration ( END) among mild ischemic stroke patients.Methods Mild ischemic stroke patients admitted in the hospital were prospectively enrolled.Univariate and multivariate Logistic recession analyses were used to analyze the demographic data, risk factors of ischemic stroke, clinical, brain imaging and laboratory data.Risk factors of END were identified.Results From June 2012 to August 2013, a total of 319 patients with mild ischemic stroke were enrolled, 45 patients (14.1%) of them experienced END.Univariate analysis showed that baseline NIHSS ( U=3522.000,P=0.000), baseline systolic blood pressure (t=2.871,P=0.004), proportion of symptomatic large artery severe stenosis or occlusion (χ2 =52.564,P=0.000) and proportion of large artery atherosclerosis among TOAST subtypes (χ2 =47.287,P=0.000) in END group were significantly higher than those in non-END group. Multivariate logistic regression analysis showed that baseline systolic blood pressure>142 mmHg (1 mmHg=0.133 kPa) (OR=3.954, 95%CI:1.693-9.236, P=0.001), symptomatic large artery severe stenosis or occlusion (OR=3.170, 95%CI:1.170-8.583, P=0.023) and baseline NIHSS (OR=2.038, 95%CI:1.359-3.057, P=0.001) were associated with END.Conclusions About 14.1% of the mild ischemic stroke patients can occur END.Baseline systolic blood pressure>142 mmHg, symptomatic large artery severe stenosis or occlusion and higher baseline NIHSS were the independent risk factors of END.

Objective To investigate the functional outcome in patients with mild ischemic stroke and to identify its risk factors for poor outcome.Methods The patients with mild ischemic stroke treated within 72 hours after onset were enrolled prospectively.According to modified Rankin Scale (mRS) scores at day 90 after onset,the patients were randomly divided into either a poor outcome group (mRS score ＞2) or a good outcome group (mRS scores 0-2).Univariate analysis and multivariate logistic regression analysis were used to compare and analyze the demographic data,vascular risk factors,clinical data,laboratory data,imaging data,and follow-up data.The risk factors for poor outcome in patients with mild ischemic stroke were identified.Results A total of 253 patients with mild ischemic stroke were enrolled,and 71 of them (28.1％) had poor outcome.Univariate regression analysis showed that the patients' proportions of age (t =2.037,P =0.043),baseline National Institutes of Health Stroke Scale (NIHSS) score (U =4 610.000,P =0.000),baseline mRS score (U =5 723.000,P =0.000),as well as previous history of ischemic stroke (x2 =4.950,P =0.026),severe symptomatic artery stenosis or occlusion (x2 =49.037,P =0.000),large artery atherosclerotic stroke (x2 =34.359,P =0.000),early neurologic deterioration (x2 =45.804,P =0.000),complicated by pneumonia (x2 =12.121,P =0.000) and recurrent ischemic stroke (x2 =14.305,P =0.000) of the poor outcome group were significantly higher than those of the good outcome group.Multivariate logistic regression analysis showed that advanced age (odds ratio [OR] 1.049,95％ confidence interval [CI] 1.012-1.086; P =0.008),higher baseline mRS score (OR,2.130,95％ CI 1.212-3.743;P=0.009),higher baseline NIHSS score (OR 1.532,95％ CI 1.064-2.206; P=0.022),severe symptomatic large artery stenosis or occlusion (OR 7.569,95％ CI 3.497-16.380; P=0.000),early neurological deterioration (OR 7.369,95％ CI 2.648-20.510; P =0.000) and recurrent ischemic stroke (OR 10.450,95％ CI 3.071-35.564; P =0.000) were the independent risk factors for poor outcome.Conclusions More than one fourth of the patients with mild ischemic stroke had poor outcome.Advanced age,higher baseline mRS score,higher baseline NIHSS score,severe symptomatic large artery stenosis or occlusion,early neurological deterioration,and recurrent ischemic stroke were the independent risk factors for poor outcome.

Uncoupling protein 4 (UCP4) is a member of the multigenic uncoupling proteins (UCPs), specific expressing in the cerebral cortex and hippocampus. UCP4 plays an important role in Parkinson's disease, multiple sclerosis, epilepsy, stroke, brain trauma and other central nervous system diseases by uncoupling, decreasing mitochondrial membrane potential,regulating Ca2+ homeostasis and oxidative stress. This article reviews UCP4 and its roles in the central nervous system diseases in order to provide certain basis for the development of UCP4targeted medication.