Prevention of posttraumatic axon sprouting by blocking collapsin response mediator protein 2-mediated neurite outgrowth and tubulin polymerization.

Epileptogenesis following traumatic brain injury (TBI) is likely due to a combination of increased excitability, disinhibition, and increased excitatory connectivity via aberrant axon sprouting. Targeting these pathways could be beneficial in the prevention and treatment of posttraumatic epilepsy. Here, we tested this possibility using the novel anticonvulsant (R)-N-benzyl 2-acetamido-3-methoxypropionamide ((R)-lacosamide [LCM]), which acts on both voltage-gated sodium channels and collapsin response mediator protein 2 (CRMP2), an axonal growth/guidance protein. LCM inhibited CRMP2-mediated neurite outgrowth, an effect phenocopied by CRMP2 knockdown. Mutation of LCM-binding sites in CRMP2 reduced the neurite inhibitory effect of LCM by ∼8-fold. LCM also reduced CRMP2-mediated tubulin polymerization. Thus, LCM selectively impairs CRMP2-mediated microtubule polymerization, which underlies its neurite outgrowth and branching. To determine whether LCM inhibits axon sprouting in vivo, LCM was injected into rats subjected to partial cortical isolation, an animal model of posttraumatic epileptogenesis that exhibits axon sprouting in cortical pyramidal neurons. Two weeks following injury, excitatory synaptic connectivity of cortical layer V pyramidal neurons was mapped using patch clamp recordings and laser scanning photostimulation of caged glutamate. In comparison with injured control animals, there was a significant decrease in the map size of excitatory synaptic connectivity in LCM-treated rats, suggesting that LCM treatment prevented enhanced excitatory synaptic connectivity due to posttraumatic axon sprouting. These findings suggest, for the first time, that LCM's mode of action involves interactions with CRMP2 to inhibit posttraumatic axon sprouting.

Delivery of health informatics education and training.

An overview is provided of education and training in health information management in the context of national information strategies. Although the article focuses upon British programmes, there are examples from North America, Australasia and other countries. Reference is made to international activities in the development of generic courses for education and training, the need for education and training, the content of courses, and methods of delivery, including Internet-based training and education. Governments and health authorities in many countries have recognized the urgent need for a highly educated and trained workforce in information management, but universities have been slow to respond, until the last few years. However, there is now a plethora of education and training programmes in North America, most European countries, and Australasia.

New opportunities for NHS librarians and information scientists.

The recent fundamental transformation in government policy on the National Health Service has far-reaching implications for all types of health-care information provision and use. This paper highlights the new opportunities, as well as the major issues, these developments have generated.

Odontohypophosphatasia: report of two cases.

Reports of a mild form of hypophosphatasia have been presented in which the oral findings were the only clinical and radiographic manifestations of the disease. It is important to support the clinical interpretations with laboratory findings in order to make a differential diagnosis from such diseases as Papillon-LeFevre Syndrome and cyclic diseases and noncyclic neutropenia. The term odontohypophosphatasia is suggested in those cases where the dental findings are the predominant manifestations of the disease.