Spreading Depression Can Be Elicited in Brain Stem of Immature But Not Adult Rats

Abstract

Spreading depression (SD), a neuronal mechanism involved in brain pathophysiology, occurs in brain areas with high neuronal density such as the cerebral cortex. By contrast, the brain stem is thought to be resistant to SD. Here we show that DC shifts resembling cortical SD can be elicited in rat brain stem by topical application of KCl but not by pricking the brain stem. However, this was only possible until postnatal day 13, and, in addition, susceptibility for SD had to be enhanced. The latter was achieved by superfusion of the brain stem for 45 min with a solution containing acetate instead of chloride ions. Transient asphyxia or hypoxia by 2 min breathing 6% O2 in N2 had a similar effect. Negative brain stem DC deflections were paralleled by an increase of extracellular potassium concentration </=40 mM and were spreading, but unlike cortical SD they were not inducible by glutamate and N-methyl-d-aspartate (NMDA). Time course and slope of brain stem SD either resembled cortical SD or were long-lasting and sustained. The latter stopped normal breathing. Different from cortical SD, negative brain stem DC deflections were changed in their slope (mostly converted into sustained shape, peak time was significantly prolonged, decline-time and duration were prolonged), but not abolished by the NMDA receptor blocker MK-801. Thus we demonstrate that the immature brain stem has the capacity to generate negative DC shifts, which could be relevant as a risk factor in newborn brain stem function.

Spinal and cortical spreading depression enhance spinal cord activity

“…However, it is shown that SD can be elicited in immature rat brainstem by topical application of KCl when the susceptibility for SD enhanced by superfusion of the brainstem with a solution containing acetate instead of chloride ions (Richter et al, 2003). In the present study, SD was elicited relatively easier in the spinal cord.…”

Enhanced Neuronal Excitability in Adult Rat Brainstem Causes Widespread Repetitive Brainstem Depolarizations with Cardiovascular Consequences

“…This is in line with observations in rat hippocampus, where microdialysis with high K + solution ignited series of recurrent SDs (Herreras and Somjen, 1993), and in rat cerebral cortex, where series of SD were observed during spreading ischemia (Windmuller et al, 2005). The relation to an elevated [K + ] e is furthermore underscored by the lack of occurrence of RDs in the immature rat brainstem, where the conditioning superfusate did not contain higher K + concentrations (Richter et al, 2003). However, two observations are noteworthy that suggest differences between mechanisms of KClevoked SD and RDs.…”

Cortical spreading depression confounds concentration-dependent pial arteriolar dilation during N-methyl-d-aspartate superfusion

“…Therefore, ␣-chloralose, an anesthetic favored in cerebrovascular studies, may render the cortex more prone to CSD during NMDA superfusion (5,23,26,27,33,34,44,46). Third, the degree of cortical maturation influences CSD susceptibility (20,21,28,41,42,48), and many studies of NMDA-induced vasodilation have traditionally been performed in immature cortex, such as in piglets.…”