Starvation and Seizures

Abstract

Acute starvation of adult rats resulted in a rise in the electroconvulsive threshold at 48 hours (P less than .10) and at 72 hours (P less than .01), but not at 24 hours. Biochemical correlates included (1) ketonemia and mild hypoglycemia in the blood; (2) a significant rise in the brain cytoplasmic phosphorylation potential and in the energy charge potential; (3) a shift in the brain cytoplasmic oxidation-reduction potential to a more oxidized state; (4) probable partial inhibitions in brain phosphofructokinase and pyruvate dehydrogenase; and (5) relatively small increases in brain sodium (4.1%), potassium (2.4%), and chloride (4.3%). No major differences were seen in brain water content or adenosine triphosphatase activity. The observed cerebral biochemical alterations are believed to be the consequence of increased ketone body utilization, although the precise relationship to the alteration in the electroconvulsive threshold remains unclear.

Modulation of substrate transport to the brain

“…The 1st kind is the increased substrate gradient across the endothelium induced by reduction of the substrate level in the brain (71). In the case of ketone bodies, this mechanism plays no role at all because ketone body levels in the brain are very low (73). In the case of ketone bodies, this mechanism plays no role at all because ketone body levels in the brain are very low (73).…”

“…This mechanism appears to be the least important because there must be narrow limits to the reduction of substrate concentration tolerated by brain cells (19). In the case of ketone bodies, this mechanism plays no role at all because ketone body levels in the brain are very low (73).…”

“…A close correlation also exists between the cerebral transport and utilization of ketone bodies (58). The normal brain concentration is about 10-20% of plasma (72,73). Therefore, ketone bodies are effectively metabolized, and the transport remains unidirectional since there is virtually no backflux.…”

Ketones: Metabolism's Ugly Duckling

“…Subsequently, a number of studies have shown an increase in the electroconvulsive threshold in rats maintained on a high-fat diet or deprived of food for 48 hours. De Vivo et al 61 found that the ratios of ATP to adenosine diphosphate (ADP) were signi cantly increased in the brains of rats fed the high- Figure 2. Production of ATP (adenosine triphosphate) in extrahepatic tissues arising from use of ketones and glucose.…”

Starving for attention, eating for excitement: assessing the ability of caloric restriction to alter kindled seizure and behavioural profiles in seizure-prone (Fast) versus seizure-resistant (Slow)rats

“…Hence, a moderate restriction in caloric intake may create an environment of reduced glucose that would shift cerebral metabolism from glucose to ketone body utilization, as well as stimulate fatty acid metabolism in the liver to offer up more ketone bodies as a fuel source (Birt et al, 1999;Sokoloff, 1999). It has also been observed that the increased ketone body metabolism punctuated by food restriction can increase sodium and potassium ATPase activity, which may serve to increase membrane potential and thereby decrease neuronal excitability (Srinivasarao et al, 1997;Schwartzkroin, 1999;Ma et al, 2007;Eiam-Ong & Sabatini, 1999;DeVivo et al, 1975). In essence, CR is a sustainable approach to induce some of the metabolic changes that accompany therapeutic fasting, while circumventing the pathology of starvation and the pitfalls of a predominantly fat diet.…”