2-Deoxy-D-glucose administration after seizures has disease-modifying effects on kindling progression.

2-deoxy-D-glucose (2DG) is a glucose analog and reversible inhibitor of glycolysis with anticonvulsant and antiepileptic effects in multiple seizure models. 2DG at a dose of 250 mg/kg intraperitoneally (IP) delays progression of repeated seizures evoked by kindling in rats when administered 30 min prior to twice daily kindling stimulation. As toxicological studies have demonstrated that repeated daily oral administration of 2DG at doses of 60-375 mg/kg/day in rats induces dose-dependent, reversible cardiac myocyte vacuolation, it was of interest to determine if 2DG also slowed kindling progression when administered at or below doses causing cardiac toxicity and at various time points after evoked seizures.

2DG and glycolysis as therapeutic targets for status epilepticus.

2-deoxy-D-glucose (2DG) is a glucose analog differing from glucose only by removal of an oxygen atom at the 2 position, which prevents the isomerization of glucose-6-phosphate to fructose-6-phosphate, and thereby reversibly inhibits glycolysis. PET studies of regional brain glucose utilization positron-emitting 18F-2DG demonstrate that brain regions generating seizures have diminished glucose utilization during interictal conditions, but rapidly transition to markedly increased glucose delivery and utilization during seizures, particularly in status epilepticus (SE). 2-deoxy-D-glucose has acute antiseizure actions in multiple in vivo and in vitro seizure models, including models of SE induced by the chemo convulsants pilocarpine and kainic acid, suggesting that focal enhanced delivery of 2DG to ictal brain circuits is a potential novel anticonvulsant intervention for the treatment of SE.

Experimental Neurotherapeutics: Surfing the Tidal Wave of New Opportunities.

The subspecialty of experimental neurotherapeutics trains neurologists in discovering and developing new treatments for neurologic diseases. Based on development of exciting new treatments for genetic and inflammatory diseases, we predict that there will be many other breakthroughs. The job market has expanded rapidly in academia, the pharmaceutical industry, government, and not-for-profit sectors; many new opportunities can be anticipated.

Diffusion Tensor Orientation as a Microstructural MRI Marker of Mossy Fiber Sprouting After TBI in Rats.

Diffusion tensor imaging (DTI) metrics are highly sensitive to microstructural brain alterations and are potentially useful imaging biomarkers for underlying neuropathologic changes after experimental and human traumatic brain injury (TBI). As potential imaging biomarkers require direct correlation with neuropathologic alterations for validation and interpretation, this study systematically examined neuropathologic abnormalities underlying alterations in DTI metrics in the hippocampus and cortex following controlled cortical impact (CCI) in rats. Ex vivo DTI metrics were directly compared with a comprehensive histologic battery for neurodegeneration, microgliosis, astrocytosis, and mossy fiber sprouting by Timm histochemistry at carefully matched locations immediately, 48 hours, and 4 weeks after injury.