ro13-9904 and Motor-Neuron-Disease

Topics: Anti-Bacterial Agents; Brachial Plexus Neuritis; Brachial Plexus Neuropathies; Ceftriaxone; Diagnosis, Differential; Female; Humans; Lyme Neuroborreliosis; Magnetic Resonance Imaging; Middle Aged; Motor Neuron Disease; Muscle Weakness; Paralysis

Some antibiotics are suggested to exert neuroprotective effects via regulation of glial responses. Attenuation of microglial activation by minocycline prevents neuronal death in a variety of experimental models for neurological diseases, such as cerebral ischemia, Parkinson's and Huntington's disease. Ceftriaxone delays loss of neurons in genetic animal models of amyotrophic lateral sclerosis through upregulation of astrocytic glutamate transporter expression (GLT-1). However, it remains largely unknown whether these antibiotics are able to protect neurons in axotomy models for progressive motor neuron diseases. Recent studies have shown that the axotomized motoneurons of the adult rat can survive, whereas those of the adult mouse undergo neuronal degeneration. We thus examined the possible effects of ceftriaxone and minocycline on neuronal loss and glial reactions in the mouse hypoglossal nucleus after axotomy. The survival rate of lesioned motoneurons at 28 days after axotomy (D28) was significantly improved by ceftriaxone and minocycline treatment. There were no significant differences in the cellular densities of astrocytes between ceftriaxone-treated and saline-treated animals. Ceftriaxone administration increased the expression of GLT-1 in the hypoglossal nucleus, while it suppressed the reactive increase of glial fibrillary acidic protein (GFAP) expression to control level. The cellular densities of microglia at D28 were significantly lower in minocycline-treated mice than in saline-treated mice. The time course analysis showed that immediate increase in microglia at D3 and D7 was not suppressed by minocycline. The present observations show that minocycline and ceftriaxone promote survival of lesioned motoneurons in the mouse hypoglossal nucleus, and also suggest that alterations in glial responses might be involved in neuroprotective actions of antibiotics.

Topics: Animals; Astrocytes; Axotomy; Ceftriaxone; Cell Survival; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Interactions; Glial Fibrillary Acidic Protein; Hypoglossal Nerve Injuries; Male; Mice; Mice, Inbred C57BL; Microglia; Minocycline; Motor Neuron Disease; Nerve Tissue Proteins; Neurons; Neuroprotective Agents

Topics: Anti-Bacterial Agents; Ceftriaxone; Humans; Motor Neuron Disease

This report summarizes what we believe to be the first verifiable case of a significant and progressive motor neuron disease (MND) consistent with amyotrophic lateral sclerosis that resolved during treatment with i.v. ceftriaxone plus oral atovaquone and mefloquine. The rationale for use of these antibiotics was (i) positive testing for Borrelia burgdorferi and (ii) red blood cell ring forms consistent with Babesia species infection. The patient has continued to be free of MND signs and symptoms for 15 months, although some symptoms consistent with disseminated Borreliosis remain.

Topics: Anti-Bacterial Agents; Atovaquone; Ceftriaxone; Drug Administration Schedule; Drug Therapy, Combination; Humans; Infusions, Intravenous; Male; Middle Aged; Motor Neuron Disease; Recovery of Function

Topics: Adult; Ceftriaxone; Humans; Male; Motor Neuron Disease; Treatment Outcome

Topics: Ceftriaxone; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Motor Neuron Disease; Treatment Outcome