No abstract

Recovery after stroke and other types of brain injury is restricted in part by the limited ability of undamaged neurons to form compensatory connections. Inosine, a naturally occurring purine nucleoside, stimulates neurons to extend axons in culture and, in vivo, enhances the ability of undamaged neurons to form axon collaterals after brain damage. The molecular changes induced by inosine are unknown, as is the ability of inosine to restore complex functions associated with a specific cortical area. Using a unilateral injury model limited to the sensorimotor cortex, we show that inosine triples the number of corticospinal tract axons that project from the unaffected hemisphere and form synaptic bouton-like structures in the denervated half of the spinal cord. These changes correlate with improved recovery in animals' ability to grasp and consume food pellets with the affected forepaw. Studies using laser-capture microdissection and microarray analysis show that inosine profoundly affects gene expression in corticospinal neurons contralateral to the injury. Inosine attenuates transcriptional changes caused by the stroke, while upregulating the expression of genes associated with axon growth and the complement cascade. Thus, inosine alters gene expression in neurons contralateral to a stroke, enhances the ability of these neurons to form connections on the denervated side of the spinal cord, and improves performance with the impaired limb.

Patients older than 65 years with osteosarcoma have a worse prognosis compared with younger patients. This older age group is characterized by a longer time lapse from the onset of symptoms to diagnosis, more metastatic cases at diagnosis, less use of limb salvage, fewer patients receiving chemotherapy, and more patients excluded from clinical trials than a younger age group.

No abstract

Despite the lack of new drugs for osteosarcoma, survival has statistically improved, especially for those patients with the worst outcome. Aggressive treatments are recommended for all patients including those with poor prognosis.