Plasma protein extravasation induced in the rat dura mater by stimulation of the parasympathetic sphenopalatine ganglion.

It has been proposed that migraine could result from a neurogenic inflammation of the dura mater. According to this theory, inflammation could be initiated by an axon reflex of nociceptive nerve fibers, but the trigger of this axon reflex remains poorly understood. Previous works have shown that parasympathetic agonists can activate mast cells and/or sensory C-fibers, inducing pain and inflammation. The aim of the present work was to determine whether the activation of intracranial parasympathetic nerve fibers could trigger an inflammatory mechanism within the rat dura mater. Activation of the intracranial parasympathetic system was achieved by electrical stimulation of the sphenopalatine ganglion (SPG). The development of a neurogenic inflammation was estimated either by microscopic examination or by quantitative measurement of plasma protein extravasation (PPE) in the dura. To determine the respective roles of the parasympathetic and sensory innervations, two groups of rats were pretreated either with atropine or with capsaicin. Stimulation of the SPG induced a PPE increase of about 200% in the stimulated side on the dura mater. Extravasated material was mainly concentrated around small blood vessels. This extravasation was significantly reduced by capsaicin pretreatment and completely abolished by atropine. Infusion of carbachol in the common carotid artery induced PPE in the ipsilateral dura comparable to that induced by electrical stimulation of the SPG. This extravasation was also blocked by atropine infusion. These data indicate for the first time that the parasympathetic nervous system can trigger a neurogenic inflammation in the dura via muscarinic cholinergic receptors. Sensory C-fibers seem to play a role in this phenomenon. With respect to the potential autonomic imbalance described in the etiology of various types of vascular headaches, such a mechanism could be important in inducing attacks.

Schwann cells modify expression of acetylcholinesterase and butyrylcholinesterase at rat neuromuscular junctions.

Using a monoclonal antibody (6.17) directed against a Schwann antigen, we have shown that Schwann cells synthesize a molecule implicated in a change of expression of synaptic cholinesterases, AChE and BChE, during muscle differentiation. In vitro, during synaptogenesis, the two enzymes are first present at developing synapses, and addition of Schwann cells to muscle-neuron co-cultures induces a disappearance of BChE, leaving only AChE activity as in the adult neuromuscular junction. This effect is inhibited by the 6.17 antibody. Thus, a molecule produced by Schwann cells is involved in the maturation of the neuromuscular synapse, in addition to the neuronal factors (CGRP, ARIA/heregulin, agrin), which are known to control the synthesis, maturation and accumulation of acetylcholine receptors and other synaptic components. In addition, in vivo, in the newborn rat, butyrylcholinesterase and acetylcholinesterase activities are initially present in equal amounts in the neural zone, but butyrylcholinesterase levels diminish sharply between 7 and 15 days after birth, the stage at which the synaptic Schwann cell membrane becomes juxtaposed with the muscle membrane.