title: Enhanced neuronal excitability in adult rat brainstem causes widespread repetitive brainstem depolarizations with cardiovascular consequences.
abstract: The brainstem of the adult rat is relatively resistant to spreading depolarization (SD) but after enhancement of excitability SD can be evoked by local application of KCl. In the present experiments, we observed that the enhanced excitability even triggers prolonged periods of repetitive depolarizations (RDs), which elicit significant cardiovascular changes. In contrast to KCl-evoked SDs with amplitudes of ∼24 mV and spreading velocity of 4 mm/min, spontaneous RDs had amplitudes of 7 to 12 mV, propagated up to 30 times faster than KCl-evoked SDs, and depolarized larger brainstem areas including the contralateral side. Similarly as SD, RDs depended on glutamatergic neurotransmission and were blocked by MK-801 or by the calcium channel blocker agatoxin. They depended on sodium channels and were blocked by tetrodotoxin. Functionally, the invasion of RDs into the spinal trigeminal and other nuclei evoked bursts of action potentials, indicating that specific neuronal systems are affected. In fact, during episodes of RDs the blood pressure and the local blood flow at the surface of the brainstem and the cortex increased substantially. Brainstem RDs did not propagate into the cerebral cortex. We propose to consider brainstem RPs as a pathophysiological mechanism whose significance for brainstem disease states should be further explored.
authors.affiliation: Institute of Physiology I/Neurophysiology, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany. frank.richter@mti.uni-jena.de
authors.forename: Frank
authors.initials: F
authors.lastname: Richter
authors.forename: Reinhard
authors.initials: R
authors.lastname: Bauer
authors.forename: Andrea
authors.initials: A
authors.lastname: Ebersberger
authors.forename: Alfred
authors.initials: A
authors.lastname: Lehmenkühler
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Schaible
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology
chemical_list: D011189:Potassium Chloride; D015740:Calcitonin Gene-Related Peptide