Effects of Peritoneal Sepsis on Rat Central Osmoregulatory Neurons Mediating Thirst and Vasopressin Release.
Sepsis is a life-threatening condition caused by the systemic inflammatory response to a bacterial infection. Although much is known about the cellular and molecular changes that characterize the peripheral inflammatory response to sepsis, almost nothing is known of the neuronal changes that cause associated perturbations in the central control of homeostasis. Osmoregulation is one of the key homeostatic systems perturbed during sepsis. In healthy subjects, systemic hypertonicity normally excites osmoreceptor neurons in the organum vasculosum laminae terminalis (OVLT), which then activates downstream neurons that induce a parallel increase in water intake and arginine vasopressin (AVP) secretion to promote fluid expansion and maintain blood pressure. However, recent studies have shown that the early phase of sepsis is associated with increased AVP levels and suppressed thirst. Here we examined the electrophysiological properties of OVLT neurons and magnocellular neurosecretory cells (MNCs) in acute in vitro preparations obtained from rats subjected to sham surgery or cecal ligation and puncture (CLP). We found that the intrinsic excitability of OVLT neurons was not affected significantly 18-24 h after CLP. However, OVLT neurons in CLP rats were hyperpolarized significantly compared with shams. Moreover, a reduced proportion of these cells displayed spontaneous electrical activity and osmoresponsiveness in septic animals. In contrast, the osmoresponsiveness of MNCs was only attenuated by CLP, and a larger proportion of these neurons displayed spontaneous electrical activity in septic animals. These results suggest that acute sepsis disrupts centrally mediated osmoregulatory reflexes through differential effects on the properties of neurons in the OVLT and supraoptic nucleus.


CONCLUSIONS
Sepsis is a life-threatening condition caused by the systemic inflammatory response to bacterial infection. Although the early phase of sepsis features impaired thirst and enhanced vasopressin release, the basis for these defects is unknown. Here, we show that cecal ligation and puncture (CLP) in rats impairs the osmoresponsiveness of neurons in the organum vasculosum lamina terminalis (OVLT; which drives thirst) and attenuates that of neurosecretory neurons in the supraoptic nucleus (SON; which secrete oxytocin and vasopressin). Notably, we found that OVLT neurons are hyperpolarized and electrically silenced. In contrast, CLP increased the proportion of SON neurons displaying spontaneous electrical activity. Therefore, CLP affects the properties of osmoregulatory neurons in a manner that can affect systemic osmoregulation.
Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4, Department of Physiology, McGill University, Montreal, Quebec, Canada H3G 1Y6.
Jerneja
J
Stare
Department of Intensive Care Medicine, Sud Essonne Hospital, F-91152 Étampes, France.
Shidasp
S
Siami
Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4.
Eric
E
Trudel
Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4.
Masha
M
Prager-Khoutorsky
General Intensive Care Medicine, Raymond Poincaré Hospital, Garches, 92380 Paris, France, and Department of Histopathology and Animal Models, Pasteur Institute, F-75015 Paris, France.
Tarek
T
Sharshar
Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4, Department of Physiology, McGill University, Montreal, Quebec, Canada H3G 1Y6, charles.bourque@mcgill.ca.
Charles W
CW
Bourque
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D004195:Disease Models, Animal; D004327:Drinking Behavior / Q000502:physiology; D008297:Male; D009474:Neurons / Q000502:physiology*; D066278:Organum Vasculosum / Q000473:pathology*; D064587:Osmoregulation / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D020318:Rats, Long-Evans; D018805:Sepsis / Q000473:pathology*; D013894:Thirst / Q000502:physiology*; D014667:Vasopressins / Q000378:metabolism*; D014882:Water-Electrolyte Balance
D014667:Vasopressins
osmoreceptor; sepsis; thirst; vasopressin