Peripherin is a 57-kDa type III neuronal intermediate filament protein that appears to play a role in neurite elongation during development and axonal regeneration. Its role in the pathogenesis of cognitive deficits caused by cerebral ischemia is unknown. The purpose of this study was to investigate the location and level of peripherin expression in the central nervous system in response to transient global cerebral ischemia, and the resultant effect of peripherin expression on the cholinergic neurons and Choline acetyltransferase (ChAT) activity in this mouse model of ischemia. Transient global cerebral ischemia was induced in C57BL/6 mice by 20-min bilateral common carotid artery occlusion (BCCAO) with microclips. The resulting impairment of spatial learning and memory was investigated by Morris water maze testing. Peripherin expression was evaluated by immunostaining and Western Blot assay of brain sections. Peripherin expression increased in neurons of the cortex, hippocampus, and thalamus after BCCAO. By double immunofluorescence staining, neurons showed a cytoplasmic co-localization of peripherin and MAP-2, but not of peripherin and GFAP. ChAT activity was determined spectrophotometrically using the assay kit. There was significantly decreased ChAT activity in the cerebral cortex, hippocampus and thalamus in mice of the BCCAO group (p<0.05), compared with the sham group. After BCCAO, peripherin overexpression was significantly correlated with reduction in ChAT activity (r=-0.929; p<0.01), spatial learning and memory were impaired, and peripherin expression was induced in neurons but not astrocytes. Thus, peripherin appears to be a participant in learning and memory impairment in mice.

Individuals with congenital monocular blindness are born without binocular vision and stereopsis, the effects of which on the brain microstructure are largely unknown. This study aims to investigate the microstructural characteristics of white matter tracts over the whole brain in congenital monocular blindness. We used T1-weighted MRI and diffusion tensor imaging (DTI) to investigate the microstructural characteristics of the brain in 16 patients with unilateral congenital microphthalmia (CM) and 16 matched normally sighted controls. The DTI-derived metrics were assessed using atlas-level analysis with FDR correction and TBSS-level analysis with threshold-free cluster enhancement correction (TFCE). CM exhibited significantly abnormal DTI-derived indices (p < 0.05, q < 0.05 of FDR correction) as follows: 1) declined fractional anisotropy (FA) in the inferior fronto-occipital fasciculus contralateral to the affected eye, bilateral inferior longitudinal fasciculus, while enhanced in the ipsilateral cingulum; 2) increased local diffusion homogeneity in the contralateral corticospinal tract while decreased in the ipsilateral superior longitudinal fasciculus; 3) reduced axial diffusivity (AD) in the body of corpus callosum. Meanwhile, the alteration tendencies of FA, AD, and radial diffusivity (RD) in the forceps major (increased FA and AD, decreased RD) and forceps minor (decreased FA and AD, increased RD) were interestingly opposite. These results reveal extensive microstructural abnormalities of WM ranging from sensory modalities to other cross-modal pathways involving language, execution, memory, emotion, fine movement, and interhemispheric communication as well. This study provides novel evidence of large-scale subcortical involvement subsequent to prolonged loss of half visual inputs, which may be associated with developmental delay and compensatory plasticity.

Parameters derived from diffusion tensor imaging (DTI) have been found to be significantly altered in the optic tracts, optic nerves, and optic radiations in patients with primary open-angle glaucoma (POAG). In this study, DTI-derived parameters were further constructed into fiber connectivity, and we investigated anatomical fiber connectivity changes within and beyond the visual pathway in POAG patients. DTI and T1-weighted magnetic resonance images were acquired in 18 POAG patients and 26 healthy controls (HC). White matter tracts based on the Brodmann atlases (BA) were constructed using the deterministic fiber tracking method. The mean fractional anisotropy (FA), fiber number (FN), and mean fiber length (FL) were measured and then evaluated using two-sample t-tests between POAG and HC. The fiber connectivity between regions was taken as the features for classifying HC and POAG using a machine learning method known as naïve Bayesian classification. The mean FA decreased in connections between visual cortex BA17/BA18 and cortex BA23/BA25/BA35/BA36, while it increased in the connections between cortex BA3/BA7/BA9 and BA5/BA6/BA45/BA25 in POAG. Classification using fibers where a significant difference in FN had been identified produced better accuracy (ACC = 0.89) than using FA or FL (ACC = 0.77 and 0.75, respectively). The FN of individual fiber connections with higher accuracy and significant changes in POAG involved brain regions associated with vision (BA19), depression (BA10/BA46/BA25), and memory (BA29). These findings strengthen the hypothesis that POAG involves changes in anatomical connectivity within and beyond the visual pathway. Classification using the machine learning method reveals that mean FN has the potential to be used as a biomarker for detecting white matter microstructure changes in POAG.