Calpain inhibition by cerebrospinal fluid and effects of calpain on intrathecal nerve tissue.
METHODS
The effects of calpain on intrathecal nerve tissue in the rabbit were investigated.


OBJECTIVE
To evaluate the chemonucleolytic side effect of calpain on nerve tissue in the event of accidental intrathecal calpain injection.


BACKGROUND
Calpain has a degradative effect on proteoglycans, and as previously shown, it is associated with chemonucleolytic action in the rabbit. However, its effect on nerve tissue in the event of accidental intrathecal injection is not clear.


METHODS
The inhibitory activity of cerebrospinal fluid against calpain was measured in human cerebrospinal fluid using mu-calpain, and in different cerebrospinal fluid fractions separated by molecular filtration. The presence of the endogenous calpain inhibitor, calpastatin, in human cerebrospinal fluid was examined by Western blotting with anticalpastatin antibody. After intrathecal application of calpain in rabbits, the spinal cord nerve tissue was examined by light microscopy.


RESULTS
Cerebrospinal fluid inhibited the enzyme reaction of calpain at its normal concentration. Immunoblotting with anticalpastatin antibody did not yield positive staining. After the intrathecal application of calpain, there was no evidence of degeneration in the nerve tissue of the spinal cord.


CONCLUSIONS
This study suggests that in the event of accidental intrathecal injection of calpain for chemonucleolysis, the enzyme activity of calpain will be neutralized by cerebrospinal fluid, and the calpain should not cause unwanted side effects in chemonucleolysis.
Kodama
Hirotaka
H
Departments of Orthopaedic Surgery and; Biochemistry, Gifu University School of Medicine, Gifu, Japan.
Shimizu
Katsuji
K
Banno
Yoshiko
Y
Nonomura
Yuka
Y
Oshita
Hidefumi
H
Akaike
Atsushi
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D002555:Cerebrospinal Fluid / Q000737:chemistry / Q000502:physiology*; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D008297:Male; D008875:Middle Aged; D009417:Nerve Tissue / Q000187:drug effects* / Q000473:pathology; D011817:Rabbits; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology
D002154:Calpain