Hepatic encephalopathy (HE) is a reversible neuropsychiatric syndrome associated with acute and chronic liver diseases. It includes a number of neuropsychiatric disturbances including impaired motor activity and coordination, intellectual and cognitive function.

Proximal nerve injury often requires nerve transfer to restore function. Here we evaluated the efficacy of end‐to‐end and end‐to‐side neurorrhaphy of rat musculocutaneous nerve, the recipient, to ulnar nerve, the donor. The donor was transected for end‐to‐end, while an epineurial window was exposed for end‐to‐side neurorrhaphy. Retrograde tracing showed that 70% donor motor and sensory neurons grew into the recipient 3 months following end‐to‐end neurorrhaphy compared to 40–50% at 6 months following end‐to‐side neurorrhaphy. In end‐to‐end neurorrhaphy, regenerating axons appeared as thick fibers which regained diameters comparable to those of controls in 3–4 months. However, end‐to‐side neurorrhaphy induced slow sprouting fibers of mostly thin collaterals that barely approached control diameters by 6 months. The motor end plates regained their control density at 4 months following end‐to‐end but remained low 6 months following end‐to‐side neurorrhaphy. The short‐latency compound muscle action potential, typical of that of control, was readily restored following end‐to‐end neurorrhaphy. End‐to‐side neurorrhaphy had low amplitude and wide‐ranging latency at 4 months and failed to regain control sizes by 6 months. Grooming test recovered successfully at 3 and 6 months following end‐to‐end and end‐to‐side neurorrhaphy, respectively, suggesting that powerful muscle was not required. In short, both neurorrhaphies resulted in functional recovery but end‐to‐end neurorrhaphy was quicker and better, albeit at the expense of donor function. End‐to‐side neurorrhaphy supplemented with factors to overcome the slow collateral sprouting and weak motor recovery may warrant further exploration.

Alzheimer's disease (AD), a progressive neurodegenerative disorder characterized by memory loss and dementia, could be a consequence of the abnormalities of cortical milieu, such as oxidative stress, inflammation, and/or accompanied with the aggregation of β-amyloid. The majority of AD patients are sporadic, late-onset AD, which predominantly occurs over 65 years of age. Our results revealed that the ferrous amyloid buthionine (FAB)-infused sporadic AD-like model showed deficits in spatial learning and memory and with apparent loss of choline acetyltransferase (ChAT) expression in medial septal (MS) nucleus. In hippocampal CA1 region, the loss of pyramidal neurons was accompanied with cholinergic fiber loss and neuroinflammatory responses including glial reaction and enhanced expression of inducible nitric oxide synthase (iNOS). Surviving hippocampal CA1 pyramidal neurons showed the reduction of dendritic spines as well. Astaxanthin (ATX), a potent antioxidant, reported to improve the outcome of oxidative-stress-related diseases. The ATX treatment in FAB-infused rats decreased neuroinflammation and restored the ChAT + fibers in hippocampal CA1 region and the ChAT expression in MS nucleus. It also partly recovered the spine loss on hippocampal CA1 pyramidal neurons and ameliorated the behavioral deficits in AD-like rats. From these data, we believed that the ATX can be a potential option for slowing the progression of Alzheimer's disease.

In traumatic brain injury (TBI) there is often compression of the cerebral cortex. Using a rat epidural bead implantation model we found that mechanical compression distorted the dendrites of underlying cortical pyramidal neurons, and that the deformed dendrites regained straight morphology in 3 days. This was accompanied by a transient increase in the phosphorylation of microtubule-associated proteins (MAPs) at sites known to destabilize microtubules, including MAP2 from 30 min to 1 h, and tau from 10 min to 12 h following compression. Immunostaining confirmed that phosphorylated MAPs were concentrated at the somata and dendrites of compressed cortical pyramidal neurons. Enzymes regulating MAP phosphorylation were found to be simultaneously altered, including downregulation of protein phosphatase 2A, but not 2B, activity from 10 min to 1 day, and transient excitatory phosphorylation of extracellular signal-regulated protein kinase 1/2 and p38/mitogen-activated protein kinase. The temporal coincidence of these events suggests that alterations of phosphatase and kinase activity underlie MAP2 and tau phosphorylation, thus causing the compressed cortical neurons to remodel their dendrites, including the proximal segments. The rapid onset of these molecular changes demonstrates that compression causes cortical neurons to undergo active changes much early than expected. The large-scale structural changes that result can alter cortical function for an extended period of time.

Using ulnar nerve as donor and musculocutaneous nerve as recipient we found earlier that end-to-side neurorrhaphy resulted in weak functional reinnervation after lengthy survival. End-to-side neurorrhaphy however is the sole choice of nerve repair at times and has the advantage of conserving donor nerve function. Here, we investigated whether myelination-enhancing agent methylcobalamin and motoneuron trophic factor pleiotrophin enhances the recovery after end-to-side neurorrhaphy. Methylcobalamin significantly increased the expression of growth associated protein 43 and S100 protein and βIII tubulin in musculocutaneous nerve 1 month after neurorrhaphy suggesting the ingrowth of ulnar axonal sprouts in reactive Schwann cell environment. Upper limb functional test, compound muscle action potential measurements, motor end plate counts, and axon and myelin analyses showed that methylcobalamin treatment alone or with pleiotrophin improved the recovery significantly, 3 and 6 months post-surgery. There were fewer axons, closer in number to that of the intact recipient nerve, found in the distal repaired nerve of the methylcobalamin-treated than that of the vehicle control, suggesting that methylcobalamin facilitates axonal maturation and eliminates supernumerary sprouts. In conclusion, our results showed that methylcobalamin does indeed enhance the recovery of peripheral nerve repaired in end-to-side configuration.