Activation of CNS circuits producing a neurogenic cystitis: evidence for centrally induced peripheral inflammation.
We present a model of neurogenic cystitis induced by viral infection of specific neuronal circuits of the rat CNS. Retrograde infection by pseudorabies virus (PRV) of neuronal populations neighboring those that innervate the bladder consistently led to a localized immune response in the CNS and bladder inflammation. Infection of bladder circuits themselves or of circuits distant from these rarely produced cystitis. Absence of virus in bladder and urine ruled out an infectious cystitis. Total denervation of the bladder, selective C-fiber deafferentation, or bladder sympathectomy prevented cystitis without affecting the CNS disease, indicating a neurogenic component to the inflammation. The integrity of central bladder-related circuits is necessary for the appearance of bladder inflammation, because only CNS lesions affecting bladder circuits, i.e., bilateral dorsolateral or ventrolateral funiculectomy, as well as bilateral lesions of Barrington's nucleus/locus coeruleus area, prevented bladder inflammation. The close proximity in the CNS of noninfected visceral circuits to infected somatic neurons would thus permit a bystander effect, leading to activation of the sensory and autonomic circuits innervating the bladder and resulting in a neurogenic inflammation localized to the bladder. The present study indicates that CNS dysfunction can bring about a peripheral inflammation.
Jasmin
L
L
Department of Neurosurgery, Georgetown University Medical Center, Washington, DC 20007, USA.
Janni
G
G
Manz
H J
HJ
Rabkin
S D
SD
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003556:Cystitis / Q000503:physiopathology* / Q000821:virology; D003714:Denervation; D005070:Evans Blue / Q000493:pharmacokinetics; D011558:Herpesvirus 1, Suid; D007031:Hypothalamus / Q000473:pathology / Q000821:virology; D008125:Locus Coeruleus / Q000473:pathology / Q000821:virology; D008297:Male; D008526:Medulla Oblongata / Q000473:pathology / Q000821:virology; D009412:Nerve Fibers / Q000201:enzymology / Q000502:physiology / Q000821:virology; D020078:Neurogenic Inflammation / Q000503:physiopathology* / Q000821:virology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009619:Nociceptors / Q000502:physiology / Q000821:virology; D010146:Pain / Q000503:physiopathology / Q000821:virology; D011537:Pruritus / Q000201:enzymology / Q000503:physiopathology / Q000821:virology; D011557:Pseudorabies / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000294:innervation / Q000473:pathology / Q000821:virology
D005070:Evans Blue; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat