Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.37 (CNPase)
 539 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diffuse traumatic brain injury (TBI) initiates secondary pathology, including inflammation and reduced myelination. Considering these injury-related pathologies, the many states of activated microglia as demonstrated by differing morphologies would form, migrate, and function in and through fields of growth-inhibitory myelin byproduct, specifically Nogo. Here we evaluate the relationship between inflammation and reduced myelin antigenicity in the wake of diffuse TBI and present the hypothesis that the Nogo-66 receptor antagonist peptide NEP(1-40) would reverse the injury-induced shift in distribution of microglia morphologies by limiting myelin-based inhibition. Adult male rats were subjected to midline fluid percussion sham or brain injury. At 2h, 6h, 1d, 2d, 7d, and 21d post-injury, immunohistochemical staining was analyzed in sensory cortex (S1BF) for myelin antigens (myelin basic protein; MBP and CNPase), microglia morphology (ionized calcium-binding adapter protein; Iba1), Nogo receptor and Nogo. Pronounced reduction in myelin antigenicity was evident transiently at 1d post-injury, as evidenced by decreased MBP and CNPase staining, as well as loss of white matter organization, compared to sham and later injury time points. Concomitant with reduced myelin antigenicity, injury shifted microglia morphology from the predominantly ramified morphology observed in sham-injured cortex to hyper-ramified, activated, fully activated, or rod. Changes in microglial morphology were evident as early as 2h post-injury, and remained at least until day 21. Additional cohorts of uninjured and brain-injured animals received vehicle or drug (NEP(1-40), i.p., 15min and 19h post-injury) and brains were collected at 2h, 6h, 1d, 2d, or 7d post-injury. NEP(1-40) administration further shifted distributions of microglia away from an injury-induced activated morphology toward greater proportions of rod and macrophage-like morphologies compared to vehicle-treated. By 7d post-injury, no differences in the distributions of microglia were noted between vehicle and NEP(1-40). This study begins to link secondary pathologies of white matter damage and inflammation after diffuse TBI. In the injured brain, secondary pathologies co-occur and likely interact, with consequences for neuronal circuit disruption leading to neurological symptoms.
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PMID:Nogo presence is inversely associated with shifts in cortical microglial morphology following experimental diffuse brain injury. 2873 37

Xiaoshuan enteric-coated capsule (XSEC) is a compound Chinese medicine widely used for the treatment of ischemic stroke. Enriched environment (EE) is a rehabilitative intervention designed to facilitate physical, cognitive, and social activity after brain injury. This study aimed to assess whether the XSEC and EE combination could provide synergistic efficacy in axonal remodeling compared to that with a single treatment after ischemic stroke using magnetic resonance imaging (MRI) followed by histological analysis. Rats were subjected to permanent middle cerebral artery occlusion and treated with XSEC and EE alone or in combination for 30 days. T2-weighted imaging and diffusion tensor imaging (DTI) were performed to examine the infarct volume and axonal remodeling, respectively. The co-localization of Ki67 with NG2 or CNPase was examined by immunofluorescence staining to assess oligodendrogenesis. The expressions of growth associated protein-43 (GAP-43) and growth inhibitors NogoA/Nogo receptor (NgR)/RhoA/Rho-associated kinase2 (ROCK2) were measured using western blot and qRT-PCR. The Morris water maze (MWM) was performed to evaluate the cognitive function. MRI and histological measurements indicated XSEC and EE individually benefited axonal reorganization after stroke. Notably, XSEC + EE decreased infarct volume compared with XSEC or EE monotherapy and increased ipsilateral residual volume compared with vehicle group. DTI showed XSEC + EE robustly increased fractional anisotropy while decreased axial diffusivity and radial diffusivity in the injured cortex, striatum, and external capsule. Meanwhile, diffusion tensor tractography revealed XSEC + EE elevated fiber density in the cortex and external capsule and increased fiber length in the striatum and external capsule compared with the monotherapies. These MRI measurements, confirmed by histology, showed that XSEC + EE promoted axonal restoration. Additionally, XSEC + EE amplified oligodendrogenesis, decreased the expressions of NogoA/NgR/RhoA/ROCK2, and increased the expression of GAP-43 in the peri-infarct tissues. In parallel to these findings, rats treated with XSEC + EE exhibited higher cognitive recovery than those treated with XSEC or EE monotherapy, as evidenced by MWM test. Taken together, our data implicated that XSEC + EE exerted synergistic effects on alleviating atrophy and encouraging axonal reorganization partially by promoting oligodendrogenesis and overcoming intrinsic growth-inhibitory signaling, thereby facilitating higher cognitive recovery.
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PMID:MRI Evaluation of Axonal Remodeling After Combination Treatment With Xiaoshuan Enteric-Coated Capsule and Enriched Environment in Rats After Ischemic Stroke. 3192 Jul 24