Postnatal maturation of cytochrome oxidase and lactate dehydrogenase activity and age-dependent consequences of lithium-pilocarpine status epilepticus in the rat: a regional histoenzymology study.
The lithium-pilocarpine (Li-Pilo) model of epilepsy reproduces some pathophysiological, temporal, and developmental features of human temporal lobe epilepsy. In this model, rates of cerebral glucose utilization measured by the [(14)C]2-deoxyglucose technique increased during the initial status epilepticus (SE) and decreased during the latent or chronic periods. To correlate these metabolic changes with the activities of the enzymes of the glycolytic and tricarboxylic acid cycle pathways, we measured by histoenzymology the regional activity of two key enzymes of glucose metabolism, lactate dehydrogenase (LDH) for the anaerobic pathway and cytochrome oxidase (CO) for the aerobic pathway coupled to oxidative phosphorylation, at various times after SE induced by Li-Pilo in 10- (P10), 21-d-old (P21) and adult rats for CO and in adult rats only for LDH. CO activity was slightly affected in P10 and P21 rats only at 4 and 24 h and normalized by 14 d after SE. In adult rats, CO activity decreased at 4 and 24 h in damaged areas, like entorhinal cortex, hippocampal CA3 area, amygdala, and thalamus. At 14 d after SE, CO activity was decreased only in entorhinal cortex and increased in brainstem regions involved in the remote control of seizures. In adult rats, LDH activity decreased at 24 h and 14 d after SE in sensorimotor and entorhinal cortex. These data show that the enzymatic equipment underlying the metabolism of glucose is not severely affected by Li-Pilo SE and confirm our previous observations concerning the relative metabolic hyperactivity of brain regions involved in the seizure circuit despite marked neuronal loss.
INSERM U 405, Université Louis Pasteur, 67085 Strasbourg, France.
Emmanuel
E
Raffo
Estelle
E
Koning
Astrid
A
Nehlig
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000201:enzymology* / Q000254:growth & development; D003576:Electron Transport Complex IV / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D008094:Lithium; D008297:Male; D018721:Muscarinic Agonists; D010862:Pilocarpine; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism*
D018721:Muscarinic Agonists; D010862:Pilocarpine; D008094:Lithium; D007770:L-Lactate Dehydrogenase; D003576:Electron Transport Complex IV; D005947:Glucose