Effect Of Cathepsin S Deficiency On Brain Damage Induced By Permanent Focal Cerebral Ischemia In Mice

Background and Purpose:As lysosomal cysteine protease,cathepsin S(CatS), could degrade intra- and extra-cellular matrix and play important roles in the major histocompatibility complex classâ…¡(MHC-â…¡) mediated antigen presentation of microglia.Some other kinds of cathepsins,including cathepsin B,have been shown to mediate ischemic neuron death.The effect of Cats in brain ischemia remains unclear. Herein,we investigated whether CatS gene knock-out(CatS^-/-) could protect permanent focal brain ischemia in mice or not.Methods:CatS^-/- and wild-type(WT )C57BL/6 mice were subjected to 24 h permanent middle cerebral artery occlusion(MCAo).The neurological deficit score,infarct volume and edema volume were determined.Immunohistochemistry of brain CatS at 6h and 24 h after MCAo was done.The differences of cerebral blood vessel supply,regional cerebral blood flow(rCBF) and physiological parameters(blood gas analysis,blood pressure,blood glucose,and hemoglobin) were investigated between the 2 mice groups. Genotyping of the CatS^-/- mice was done with polymerase chain reaction(PCR).Results:There were no significant differences of the physiological parameters during MCAo between gene knock-out mice and WT mice,as well as cerebrovascular perfusion anatomy and rCBF during 60 min MCAo.The neurological outcome,cerebral infarct volume and brain edema volume 24 h after brain ischemia did not differ between those 2 kinds of mice.The result of immunohistochemistry showed the expression of CatS did not change after 6h or 24 h MCAo.Accidently,we found 7/15(46.7%) CatS^-/- mice developed hydrocephalus while none of the wild type mice had hydrocephalus(p=0.008).The mice with hydrocephalus were excluded from data analysis.Conclusion:1.CatS gene knock-out did not provide protective effect against permanent focal brain ischemia.2.CatS gene knock-out could lead to spontaneous hydrocephalus.