Isoniazid induced seizures and cerebral cortical and cerebellar energy metabolism.
Isoniazid is a useful chemical convulsant in that metabolic events associated with the preseizure state can be easily examined. In the present study, net levels of glucose, glycogen, ATP, and phosphocreatine were measured using enzymatic techniques in control mice, and in those injected with isoniazid. Results from this study showed a differential effect of isoniazid on cells from the cerebral cortex and the cerebellum. In the preseizure stage, the high energy phosphates ATP and phosphocreatine were decreased in layer 1 and the pyramidal cell layer of the cerebral parietal cortex, but were unchanged in the cerebellum. At the onset of seizures, metabolites were decreased not only in cortical layers, but in the molecular layer and Purkinje cell rich layer of the cerebellum as well. The somewhat delayed response of the cerebellum emphasizes the differential nature of metabolism in various brain regions. Such a delay in cerebellar energy response to perturbation may be conducive to the seizure state. In another series of mice, either sodium valproate or clonazepam was administered prior to isoniazid, and metabolite studies repeated. Results showed that at a time when each anticonvulsant acted to eliminate overt seizure activity, the reduction in ATP and phosphocreatine was not as great as it was in seizing mice treated with isoniazid alone.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002525:Cerebellar Cortex / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D002998:Clonazepam / Q000627:therapeutic use; D004734:Energy Metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007538:Isoniazid; D051379:Mice; D010725:Phosphocreatine / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced*; D014635:Valproic Acid / Q000627:therapeutic use
D010725:Phosphocreatine; D002998:Clonazepam; D014635:Valproic Acid; D000255:Adenosine Triphosphate; D006003:Glycogen; D005947:Glucose; D007538:Isoniazid