The repair of peripheral nerve laceration injury to obtain optimal function recovery remains a big challenge in the clinic. Misdirection of regenerating axons to inappropriate target, as a result of forced mismatch of endoneurial sheaths in the case of end-to-end nerve anastomosis or nerve autografting, represents one major drawback that limits nerve function recovery. Here we tested whether tubulation repair of a nerve defect could be beneficial in terms of nerve regeneration accuracy and nerve function. We employed sequential retrograde neuronal tracing to assess the accuracy of motor axon regeneration into the tibial nerve after sciatic nerve laceration and entubulation in adult Sprague-Dawley rats. In a separate cohort of rats with the same sciatic nerve injury/repair protocols, we evaluated nerve function recovery behaviorally and electrophysiologically. The results showed that tubulation repair of the lacerated sciatic nerve using a 3-6-mm-long bioabsorbable guidance conduit significantly reduced the misdirection of motor axons into the tibial nerve as compared to nerve autografting. In addition, tubulation repair ameliorated chronic flexion contracture. This study suggests that tubulation repair of a nerve laceration injury by utilizing a bioresorbable nerve guidance conduit represents a potential substitute for end-to-end epineurial suturing and nerve autografting.

Alzheimer's disease (AD) is characterized by the presence of extracellular amyloid β plaques and intraneuronal neurofibrillary tangles of hyperphosphorylated microtubule‐associated protein tau in the brain. Aggregation of transactive response DNA‐binding protein of 43 kDa (TDP‐43) in the neuronal cytoplasm is another feature of AD. However, how TDP‐43 is associated with AD pathogenesis is unknown. Here, we found that casein kinase 1ε (CK1ε) phosphorylated TDP‐43 at Ser403/404 and Ser409/410. In AD brains, the level of CK1ε was dramatically increased and positively correlated with the phosphorylation of TDP‐43 at Ser403/404 and Ser409/410. Overexpression of CK1ε promoted its cytoplasmic aggregation and suppressed TDP‐43‐promoted tau mRNA instability and tau exon 10 inclusion, leading to an increase of tau and 3R‐tau expressions. Levels of CK1ε and TDP‐43 phosphorylation were positively correlated with the levels of total tau and 3R‐tau in human brains. Furthermore, we observed, in pilot immunohistochemical studies, that the severe tau pathology was accompanied by robust TDP‐43 pathology and a high level of CK1ε. Taken together, our findings suggest that the elevation of CK1ε in AD brain may phosphorylate TDP‐43, promote its cytoplasmic aggregation and suppress its function in tau mRNA processing, leading to acceleration/exacerbation of tau pathology. Thus, the elevation of CK1ε may link TDP‐43 to tau pathogenesis in AD brain.

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Neurogenesis in the hippocampus continues throughout adult life and can be regulated by the local microenvironment. To determine whether denervation stimulates neurogenesis in hippocampus, proliferation, migration, and differentiation of local neural stem cells (NSCs) in dentate gyrus was investigated after fimbria fornix transection. In the denervated hippocampus, NSCs proliferated markedly and migrated along the subgranular layer, and more newborn cells differentiated into neurons or astrocytes. After denervation, more newborn cells in the deafferented hippocampus expressed Brn-4 and differentiated into beta-Tubulin III positive neurons. It is concluded that the local NSCs in hippocampus may proliferate and migrate into granule cell layer, in which changes in the deafferented hippocampus provided a suitable microenvironment for hippocampal neurogenesis and the increased Brn-4 in denervated hippocampus may be involved in this process.