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Gulf War illness: Effects of repeated stress and pyridostigmine treatment on blood brain barrier





Behav Brain Res. 2009 Nov 5;203(2):207-14. Epub 2009 May 9.


Gulf War illness: Effects of repeated stress and pyridostigmine treatment on blood-brain barrier permeability and cholinesterase activity in rat brain.


Amourette C, Lamproglou I, Barbier L, Fauquette W, Zoppe A, Viret R, Diserbo M. Département de Radiobiologie et Radiopathologie, Centre de Recherches Emile Pardé 24, Avenue des maquis du Grésivaudan, BP87 - 38702 La Tronche Cedex, France. This email address is being protected from spambots. You need JavaScript enabled to view it.



After the first Persian Gulf War, many soldiers have complained of a variety of symptoms designated as "Gulf War Illness". Among several factors, implication of pyridostigmine (PB) in late cognitive dysfunction is highly likely. As a hypothesis to explain these behavioural disorders is a potentiation of the operational stress effects by pyridostigmine. We have previously described that repeated stress combined to pyridostigmine treatment induces learning dysfunction linked to genomic cerebral modifications [Barbier L, Diserbo M, Lamproglou I, Amourette C, Peinnequin A, Fauquette W. Repeated stress in combination with pyridostigmine: part II-changes in selected cerebral genes expression. Behav Brain Res 2009;197:292-300; Lamproglou I, Barbier L, Diserbo M, Fauvelle F, Fauquette W, Amourette C. Repeated stress in combination with pyridostigmine: part I-long-term behavioural consequences. Behav Brain Res 2009;197:301-10]. In the present study, using the same experimental model, we attempted to determine if such modifications are linked to a central passage of pyridostigmine under stress. Indeed it is known that exposure to stress can disrupt blood-brain barrier (BBB) and thereby increase the neurotoxicity induced by chemicals in many cerebral areas. Adult rats were subjected to repeated stress based on a modification of the pole climbing avoidance technique and treated daily by PB (1.5mg/kg/day, oral in water), for two 5-day periods separated by 2-day rest. Just after the last stress session, (3)H-pyridostigmine was administered as a tracer to evaluate BBB breakdown. In brain micro-punches and brain coronal cryosections, we failed to detect any radioactivity in animals chronically stressed and treated by pyridostigmine. Accordingly, no change of ChE activity was noted in any brain area studied. It thus appears that, in our experimental model, pyridostigmine induces effects on central nervous system, but these effects do not seem to be mediated by a central passage of pyridostigmine linked to a BBB opening under stress. These results suggest that pyridostigmine may have central effects, under stress, via indirect mechanisms emerging from a peripheral pathway.


PMID: 19433115 [PubMed - indexed for MEDLINE]










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  • The anti-nerve gas drug pyridostigmine bromide (PB) belongs to a class of compounds called "cholinesterase inhibitors" which interfere with the functioning of the brain and nervous system and have repeatedly been linked to Gulf War syndrome.

    The blood-brain barrier (BBB) is a protective coating around the brain that selectively allows nutrients and certain other chemicals into the brain while keeping out those that could cause damage. Damage to the BBB itself is associated with increased susceptibility to denegerative brain injury due to chemical exposures. This study however indicates that a breakdown in the BBB due to stress is not the mechanism by which PB causes symptoms in Gulf War syndrome. Instead the researchers suggest effects on the brain due to PB exposure are caused by mechanisms originating from the peripheral nervous system (the nervous system excluding the brain and spinal cord).

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