Myeloperoxidase (MPO) is a pro-inflammatory enzyme abundantly secreted by activated myeloid cells after stroke. We show that when MPO activity is either blocked by the specific inhibitor 4-aminobenzoic acid hydrazide (ABAH) in wildtype (WT) mice or congenitally absent (MPO), there was decreased cell loss, including degenerating neurons and oligodendrocytes, in the ischemic brains compared to vehicle-treated WT mice after stroke. MPO inhibition also reduced the number of activated myeloid cells after ischemia. MPO inhibition increased cytoprotective heat shock protein 70 (Hsp70) by 70% and p-Akt by 60%, while decreased the apoptotic marker p53 level by 62%, compared to vehicle-treated mice after ischemia. Similarly, MPO inhibition increased the number of Hsp70/NeuN cells after stroke by 60%. Notably, MPO inhibition significantly improved neurological outcome compared with the vehicle-treated group after stroke. We further found longer treatment periods resulted in larger reduction of infarct size and greater neurobehavioral improvement from MPO inhibition, even when given days after stroke. Therefore, MPO inhibition with ABAH or MPO deficiency creates a protective environment that decreased inflammatory cell recruitment and increased expression of survival factors to improve functional outcome. MPO inhibition may represent a promising therapeutic target for stroke therapy, possibly even days after stroke has occurred.
Background The pathology of Parkinson’s disease leads to morphological changes in brain structure. Currently, the progressive changes in gray matter volume that occur with time and are specific to patients with Parkinson’s disease, compared to healthy controls, remain unclear. High-tesla magnetic resonance imaging might be useful in differentiating neurological disorders by brain cortical changes. Purpose We aimed to investigate patterns in gray matter changes in patients with Parkinson’s disease by using an automated segmentation method with 7-tesla magnetic resonance imaging. Material and Methods High-resolution T1-weighted 7 tesla magnetic resonance imaging volumes of 24 hemispheres were acquired from 12 Parkinson’s disease patients and 12 age- and sex-matched healthy controls with median ages of 64.5 (range, 41–82) years and 60.5 (range, 25–74) years, respectively. Subgroup analysis was performed according to whether axial motor symptoms were present in the Parkinson’s disease patients. Cortical volume, cortical thickness, and subcortical volume were measured using a high-resolution image processing technique based on the Desikan-Killiany-Tourville atlas and an automated segmentation method (FreeSurfer version 6.0). Results After cortical reconstruction, in 7 tesla magnetic resonance imaging volume segmental analysis, compared with the healthy controls, the Parkinson’s disease patients showed global cortical atrophy, mostly in the prefrontal area (rostral middle frontal, superior frontal, inferior parietal lobule, medial orbitofrontal, rostral anterior cingulate area), and subcortical volume atrophy in limbic/paralimbic areas (fusiform, hippocampus, amygdala). Conclusion We first demonstrated that 7 tesla magnetic resonance imaging detects structural abnormalities in Parkinson’s disease patients compared to healthy controls using an automated segmentation method. Compared with the healthy controls, the Parkinson’s disease patients showed global prefrontal cortical atrophy and hippocampal area atrophy.
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