Seizure-Induced Damage to Substantia Nigra and Globus Pallidus is Accompanied by Pronounced Intra- and Extracellular Acidosis

Status epilepticus of >30-min duration in rats gives rise to a conspicuous lesion in the substantia nigra pars reticulata (SNPR) and globus pallidus (GP). The objective of the present study was to explore whether the lesion, which encompasses necrosis of both neurons and glial cells, is related to intra- and extracellular acidosis. Using the flurothyl model previously described to produce seizures, we assessed regional pH values with the autoradiographic 5,5-dimethyl[2-¹⁴C]oxazolidine-2,4-dione technique. Regional pH values were assessed in animals with continuous seizures for 20 and 60 min, as well as in those allowed to recover for 30 and 120 min after seizure periods of 20 or 60 min. In additional animals, changes in extracellular fluid pH (pHe) were measured with ion-selective microelectrodes, and extracellular fluid (ECF) volume was calculated from the diffusion profile for electrophoretically administered tetramethylammonium. In structures such as the neocortex and the hippocampus, which show intense metabolic activation during seizures, status epilepticus of 20- and 60-min duration was accompanied by a reduction of the “composite” tissue pH (pH_t) of 0.2–0.3 unit. Recovery of pH_t was observed upon termination of seizures. In SNPR and in GP, the acidosis was marked to excessive after 20 and 60 min of seizures (ΔpH_t ≈ 0.6 after 60 min). In these structures, recovery of pH_t was observed after 20 min of seizures, but after 60 min of seizures, a lingering acidosis was observed in SNPR. During the seizures, pH_e in the neocortex fell by ∼0.2 unit. In SNPR and GP, pH_e fell to much lower values (mean ΔpH_e ∼ 0.5–0.6), but ECF volume was essentially unaltered. For SNPR we calculated an average intracellular pH of 6.2 after 60 min of seizures. We conclude that lactic acidosis is one important pathogenic factor in the development of the pannecrotic lesion in SNPR and GP.