The Effect of Hypotension on Brain Energy State during Prolonged Neonatal Seizure

Abstract

Clinical and experimental evidence show that systemic hypotension may occur during the course of prolonged seizure (1-3). Nonetheless, the physiologic and metabolic consequences of hypotension on the outcome of neonatal seizure is unclear (4). Because metabolic demands on the brain increase greatly during seizure, it is hypothesized that even a modest reduction in CBF produces relative ischemia and further tissue damage.Autoregulation of CBF ordinarily maintains cerebral perfusion during systemic hypotension (5, 6), but may be impaired during seizure (4, 7). However, use of the term, autoregulation, may be inappropriate since the response of the cerebral circulation to seizure is not a simple maintenance of blood flow, but rather a sustained increase of 150-200% (8,9). The goal of this study was to determine whether the expected compensatory increase in CBF which occurs during seizure is affected by moderate hypotension and whether there is subsequent compromise of brain energy state.

Nuclear Magnetic Resonance Spectroscopy of Seizure States

“…Changes in brain energy stores were not affected by glucose availability, although differences in alanine, glycine, and P-hydroxybutyrate were found in the 'H extracts. Hypotension had little effect on the 31P changes (Cowan et al, 1987).…”

“…A 31P MRS study of neonatal dog brain documented similar changes (Young et al, 1985). A subsequent study of the same preparation found that seizure discharge produced by electroshock was followed by only slow return of PCr and Pi to control levels, a phenomenon attributed by the authors to low endogenous stores of high-energy phosphates or less developed pathways for their regeneration in the immature brain (Young et al, 1987~).…”

Seizures in the neonatal period

“…A hipótese atualmente mais discutida para explicar lesão cerebral pós-crise prolongada é a excitotoxidade, em que a liberação excessiva de aminoáci-dos excitatórios (glutamato, aspartato, quisqualato e ácido caínico), estimulando seus receptores pós-sinápticos, determinam alterações iônicas que resultam em acúmulo de cálcio intracelular 16 . Estudos utilizando espectroscopia por ressonância nuclear magnética sugerem que as crises neonatais não determinam alterações metabólicas e/ou hipoperfusão cerebral, a menos que ocorra hipoxemia significativa ou lactoacidose extrema 17 . Trabalhos experimentais reforçam estas observações clínicas, demonstrando não existirem evidências de que crises breves produzam lesão cerebral no animal imaturo 18,19 , exceto se o mesmo já possuir seu SNC previamente exposto a outros insultos 20 .…”