Routes of entrance of tetanus toxin into the central nervous system and some problems connected with the pathogenesis of experimental tetanus part II: Experiments on mice, guinea pigs, rabbits and cats

1962 ◽  
Vol 52 (2) ◽  
pp. 894-898 ◽  
Author(s):  
G. N. Kryzhanovskii ◽  
L. A. Pevnitskii ◽  
V. N. Grafova ◽  
A. A. Polgar
1929 ◽  
Vol 50 (3) ◽  
pp. 365-370 ◽  
Author(s):  
Richard E. Shope ◽  
Paul A. Lewis

The experimental data collected during this study of a transmissible type of paralysis developing in tuberculous guinea pigs indicate the condition to be a true tuberculous meningitis. We have been able to rule out the possibility that it is due to a non-tuberculous infection of the central nervous system caused by Roemer's virus, or by an atypical herpes virus, or by some bacterium other than the tubercle bacillus. Roemer's virus and herpes could be eliminated from consideration when Berkefeld N filtrates of infectious brain emulsions proved incapable of reproducing the disease. Furthermore, rabbits could be infected as they cannot with Roemer's virus, and the disease elicited in rabbits bears no semblance to herpes encephalitis. No organism other than the tubercle bacillus could be obtained on culturing brain or brain emulsions from experimental cases, and no others were seen in examining fresh smear preparations from the central nervous system. In a modified Noguchi medium a tubercle bacillus possessing atypical staining properties was obtained. This organism was capable of producing the typical paralytic disease when injected intracerebrally into guinea pigs, and also generalized tuberculosis in animals inoculated subcutaneously with it. Typical tuberde bacilli were readily demonstrable in sections of the meninges from animals with the disease, and culture of pieces of brain on Dorset's egg medium usually yielded a growth of tubercle bacilli. Only in the first of the experimental passages, on the other hand, was it possible to demonstrate acid-fast organisms in fresh smear preparations from the central nervous system. This fact and the attributes of the atypically staining organisms encountered in the cultures in Noguchi media will be considered more fully in a subsequent publication. In view of the much discussed question of the filtrability of the tubercle bacillus our observations concerning the failure of this organism to pass a Berkefeld N filter are of interest. No animal in our series inoculated intracerebrally with brain emulsion from either a "spontaneous" or experimental case of tuberculous meningitis failed to develop meningitis, and that rather acutely, while no animal in our series injected with a Berkefeld filtrate of brain emulsion has developed tuberculous meningitis or any other form of tuberculosis. In connection with this observation it must be recalled that the organism was atypical in respect to its staining qualities at least.


1988 ◽  
Vol 65 (5) ◽  
pp. 2024-2029 ◽  
Author(s):  
P. J. Mauser ◽  
N. H. Edelman ◽  
R. W. Chapman

The central nervous system (CNS) plays an important role in the reflex control of bronchomotor tone, but the relevant neurotransmitters and neuromodulators have not been identified. In this study we have investigated the effect of histamine. Anesthetized male guinea pigs were prepared with a chronically implanted intracerebroventricular (icv) cannula and instrumented for the measurement of pulmonary resistance (RL), dynamic lung compliance (Cdyn), tidal volume (VT), respiratory rate (f), blood pressure (BP), and heart rate (HR). Administration of histamine (2-30 micrograms) icv caused a significant (P less than 0.05) reduction of Cdyn with no change in RL, VT, and f. At a dose of 100 micrograms icv, histamine caused an increase in RL (202 +/- 78%), a reduction of Cdyn (77 +/- 9%), an increase in f (181 +/- 64%), and a reduction of VT (53 +/- 18%). There were no changes in BP and HR after 100 micrograms of icv histamine. In contrast, intravenous administration of histamine (0.1-2 micrograms/kg) caused a dose-dependent decrease in Cdyn and increase in RL that was associated with tachypnea at each bronchoconstrictor dose. Intravenous histamine (2 micrograms/kg) produced a fall in BP and an increase in HR. The bronchoconstrictor responses to icv histamine were completely blocked by vagotomy and significantly reduced by atropine (0.1 mg/kg iv), whereas vagotomy and atropine did not block the bronchospasm due to intravenous histamine. Additional studies indicated that the pulmonary responses due to icv histamine (100 micrograms) were blocked by pretreatment with the H1-antagonist chlorpheniramine (1 and 10 micrograms, icv). These data indicate that histamine may serve a CNS neurotransmitter function in reflex bronchoconstriction in guinea pigs.


1990 ◽  
Vol 271 (1) ◽  
pp. 87-91 ◽  
Author(s):  
P Beaude ◽  
A Delacour ◽  
B Bizzini ◽  
D Domuado ◽  
M H Remy

Attempt to replace enzymes in a number of fatal lysosomal storage disease involving the central nervous system have as yet been unsuccessful owing to the impermeability of the blood/brain barrier to macromolecules. In order to treat storage disease due to enzyme deficiencies, we investigated the feasibility of transporting an enzyme into the central nervous system without crossing the blood/brain barrier. Using the B-IIb fragment of tetanus toxin (because it is involved in recognition by the nerve-cell endings), retrograde axonal transport toward the spinal cord and trans-synaptic movement, and glucose oxidase as a marker, we demonstrated that a non-toxic enzyme-vector conjugate was taken up by axon terminals. After injection into the gastrocnemius muscle, the B-IIb-glucose oxidase conjugate was detected, both histologically and electrochemically, distally to a ligature on the sciatic nerve. Thus the B-IIb fragment could serve as a vector for glucose oxidase transport into the central nervous system. It was also verified that the transported enzyme retained its activity. Transport of this 150 kDa molecule by fragment B-IIb of tetanus toxin suggests that other enzymes of a lesser molecular mass may also be transported.


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