No abstract

The diagnostic and prognostic potential of an onco-metabolite, 2-hydroxyglutarate (2HG) as a proton magnetic resonance spectroscopy (1H-MRS) detectable biomarker of the isocitrate dehydrogenase (IDH)-mutated (IDH-MT) gliomas has drawn attention of neuroradiologists recently. However, due to severe spectral overlap with background signals, quantification of 2HG can be very challenging. In this technical review for neuroradiologists, first, the biochemistry of 2HG and its significance in the diagnosis of IDH-MT gliomas are summarized. Secondly, various 1H-MRS methods used in the previous studies are outlined. Finally, wereview previous in vivo studies, and discuss the current status of 1H-MRS in the diagnosis of IDH-MT gliomas.

Neurogenesis persists in the adult mammalian brain and can be a target for modulation for therapeutic purposes. This study investigated the effect of a Polygala tenuifolia root extract on the proliferation of a stem cell population in the rat hippocampus. The root extract of P. tenuifolia (2 mg/kg/day, 14 times intraperitoneal injections) increased the incorporation of bromodeoxyuridine (BrdU) into cells in the hippocampal CA1 region. This activity was enriched in the saponin-containing fraction. The majority of cells labelled with BrdU were immunoreactive to nestin or Tuj1 and the percentages of nestin/BrdU- and Tuj1/BrdU-double positive cells were increased by the P. tenuifolia root extract, suggesting that the P. tenuifolia root extract promotes the proliferation of neural stem cells. In addition, this extract promoted the neurite outgrowth of rat neuronal precursor cells, HiB5. These activities of P. tenuifolia root extract may contribute to the therapeutic benefits of herbal medicines containing P. tenuifolia root for the treatment of patients with insomnia, neurosis and dementia.

Berberine, an isoquinoline alkaloid component of Coptidis Rhizoma (goldenthread) extract, has been reported to have therapeutic potential for central nervous system disorders such as Alzheimer's disease, cerebral ischemia, and schizophrenia. We have previously shown that berberine promotes the survival and differentiation of hippocampal precursor cells. In a memory-impaired rat model induced by ibotenic acid injection, the survival of pyramidal and granular cells was greatly increased in the hippocampus by berberine administration. In the present study, we investigated the effects of berberine on neurite outgrowth in the SH-SY5Y neuronal cell line and axonal regeneration in the rat peripheral nervous system (PNS). Berberine enhanced neurite extension in differentiating SH-SY5Y cells at concentrations of 0.25-3 μg/mL. In an injury model of the rat sciatic nerve, we examined the neuroregenerative effects of berberine on axonal remyelination by using immunohistochemical analysis. Four weeks after berberine administration (20 mg/kg i.p. once per day for 1 week), the thickness of remyelinated axons improved approximately 1.4-fold in the distal stump of the injury site. Taken together, these results indicate that berberine promotes neurite extension and axonal regeneration in injured nerves of the PNS.

Neuregulin 1 (NRG1) and epidermal growth factor receptor (ErbB) signaling pathways control Schwann cells during axonal regeneration in an injured peripheral nervous system. We investigated whether a persistent supply of recombinant NRG1 to the injury site could improve axonal growth and recovery of sensory and motor functions in rats during nerve regeneration. We generated a recombinant adenovirus expressing a secreted form of EGF-like domain from Heregulinβ (sHRGβE-Ad). This virus, sHRGβE-Ad allowed for the secretion of 30-50 ng of small sHRGβE peptides per 10(7-8) virus particle outside cells and was able to phosphorylate ErbB receptors. Transduction of the concentrated sHRGβE-Ad into an axotomy model of sciatic nerve damage caused an effective promotion of nerve regeneration, as shown by histological features of the axons and Schwann cells, as well as increased expression of neurofilaments, GAP43 and S100 in the distal stump of the injury site. This result is consistent with longer axon lengths and thicker calibers observed in the sHRGβE-Ad treated animals. Furthermore, sensory and motor functions were significantly improved in sHRGβE-Ad treated animals when evaluated by a behavioral test. These results suggest a therapeutic potential for sHRGβE-Ad in treatment of peripheral nerve injury.