Extravasation of staphylococcal alpha-toxin in normal and injured CNS regions lacking blood-brain barrier function: observations after ventral root replantation.
Staphylococcus aureus plays an important role as a bacterial pathogen after traumatic injury. The majority of isolated strains produces alpha-toxin, a 33-kDa protein, with membrane-damaging and lethal effects. The central nervous system (CNS) has been considered as the possible target for the lethal action of this toxin. A transfer of alpha-toxin across an intact blood-brain barrier (BBB) is however unlikely. The aim of the present study was to determine if alpha-toxin is accumulated in CNS regions which lack the BBB function. The distribution of alpha-toxin after intravascular injections, in normal mice and rats as well as in rats subjected to ventral root replantation, was assessed using immunogold technique. The results show that, although alpha-toxin does not cross the BBB, alpha-toxin-like immunoreactivity could be detected in the area postrema and at the optic nerve-retinal junction. Extravasation of alpha-toxin was also shown to occur in the spinal cord even 22 months after ventral root replantation. This finding suggests that axon regeneration after ventral root replantation takes place in a macromolecular environment which is totally different from the normal CNS. The implications of vascular spread of alpha-toxin to regions devoid of BBB function are discussed in relation to the bacterial infections which might complicate severe spinal injuries.
Sjögren
A M
AM
Department of Bacteriology, Karolinska Institutet, Stockholm, Sweden.
Thelestam
M
M
Blomqvist
L
L
Lindå
H
H
Remahl
S
S
Risling
M
M
D000818:Animals; D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000502:physiology*; D005260:Female; D006460:Hemolysin Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009416:Nerve Regeneration / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012092:Replantation; D013116:Spinal Cord / Q000378:metabolism* / Q000648:ultrastructure; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology; D013126:Spinal Nerve Roots / Q000601:surgery
D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; C021091:staphylococcal alpha-toxin