benzofurans and Demyelinating-Diseases

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). The disease mechanisms driving progressive MS remain unresolved. Without this information, current therapeutic strategies are unsatisfactory in preventing disease progression. Our previous work revealed that DL-3-n-butylphthalide (NBP) treatment reduced demyelination in an ethidium bromide mouse model of demyelination. Here, we examine the effect of NBP in the cuprizone model of demyelination by evaluating the pathologic, functional, and behavioral consequences of treatment with NBP.. Forty mice were divided randomly into 4 groups: a normal diet group, a cuprizone diet group, and two NBP groups (10 and 20 mg/kg). CNS infiltration by microglia, axon health and myelination were assessed using immunohistochemistry and electron microscopy, and the levels of cytoplasmic complexes were assessed by Western blotting.. The results showed the neuroprotective effects of the NBP included suppressing the microglia activation through inhibition of nuclear factor-κB (NF-κB) expression, thus decreasing activation of the NF-κB signaling pathway. In particular, myelin density was increased due to an increased mean number of mature oligodendrocytes (OLs) in the high-dose NBP (20 mg/kg) subgroup through reduced oligodendrocyte apoptosis. Meanwhile, increased expression of myelin sheath proteins, including proteolipid protein (PLP) and myelin basic protein (MBP), was observed in the same subgroup.. These data suggest that NBP may not only have anti-inflammatory properties but also promote the survival of OLs in a mouse cuprizone model of demyelination. NBP may have a potential role in the treatment of MS.

Topics: Animals; Astrocytes; Axons; Benzofurans; Corpus Callosum; Cuprizone; Demyelinating Diseases; Disease Models, Animal; Gene Expression Regulation; Male; Mice; Mice, Inbred C57BL; Microglia; Multiple Sclerosis; Myelin Sheath; Neuroprotective Agents; NF-kappa B; Oligodendroglia; Signal Transduction

Demyelinating diseases is common in neurology department, but its treatment is still not clear. A 40-year-old male who was addicted in heroin was hospitalized and presented worsening altered mental status in hospital. Brain magnetic resonance imaging (MRI) revealed a symmetrical diffuse long T1 and long T2 time abnormalities in the white matter of cerebral hemispheres which indicated demyelination. High-dose intravenous methylprednisolone was not effective as expected. However, after treatment with intravenous Dl-3-n-butylphthalide for 7 days, the patient's symptoms and features of electroencephalogram (EEG) and MRI improved. Hence, ethidium bromide was used in a rat model to evaluate the positive effects of Dl-3-n-butylphthalide in demyelinating diseases. The results indicated that Dl-3-n-butylphthalide prevented white matter from demyelinating by regulating apoptosis through multiple approaches.

Topics: Adult; Animals; Benzofurans; Brain; Demyelinating Diseases; Disease Models, Animal; Electroencephalography; Humans; Magnetic Resonance Imaging; Male; Methylprednisolone; Radiography; Rats, Sprague-Dawley; Treatment Outcome

The actions of psoralens, benzofurans, acridinons and coumarins on the ionic currents in intact myelinated nerve fibres were investigated. All 6 substances blocked the potassium currents in a time-dependent manner, producing so-called K+ transients. Only 5-methoxypsoralen is a largely selective blocker of predominantly the axolemmal potassium channels, which is the characteristic required by our previously proposed working hypothesis for the mechanism of potassium-channel blockers in demyelinating diseases, in particular multiple sclerosis. If the observed K+ transients were to arise by blocking of the potassium channels of the Schwann cell, that is, by the periaxonal accumulation of K+ and a resulting collapse of the electromotive driving force for potassium-ions, according to a modified version of our previous hypothesis the other substances tested could also have a beneficial effect on the impaired impulse conduction in demyelinated axons. In this case a large number of new potential drugs would be available for the symptomatic therapy of MS.

Topics: 5-Methoxypsoralen; Acridines; Animals; Benzofurans; Biophysical Phenomena; Biophysics; Coumarins; Demyelinating Diseases; In Vitro Techniques; Methoxsalen; Models, Neurological; Multiple Sclerosis; Nerve Fibers, Myelinated; Neural Conduction; Organophosphorus Compounds; Potassium Channel Blockers; Ranvier's Nodes; Umbelliferones; Xenopus laevis

Topics: Amiodarone; Angina Pectoris; Benzofurans; Demyelinating Diseases; Humans; Male; Middle Aged; Nervous System Diseases