Calcium-mediated proteolytic damage in white matter of hydrocephalic rats?

Hydrocephalus is a pathological dilatation of the cerebrospinal fluid (CSF) -containing ventricles of the brain. Damage to periventricular white matter is multifactorial with contributions by chronic ischemia and gradual physi cal distortion. Acute ischemic and traumatic brain injuries are associated with calcium-dependent activation of proteolytic enzymes. We hypothesized t hat hydrocephalus is associated with calcium ion accumulation and proteolyt ic enzyme activation in cerebral white matter Hydrocephalus was induced in immature and adult rats by injection of kaolin into the cisterna magna and several different experimental approaches were used. Using the glyoxal bis (2-hydroxyanil) method, free calcium ion was detected in periventricular wh ite matter at sites of histological injury. Western blot determinations sho wed accumulation of calpain I (mu -calpain) and immunoreactivity for calpai n I was increased in periventricular axons of young hydrocephalic rats. Pro teolytic cleavage of a fluorogenic calpain substrate was demonstrated in wh ite matter. Immunoreactivity for spectrin breakdown products was detected i n scattered callosal axons of young hydrocephalic rats. The findings suppor t the hypothesis that periventricular white matter damage associated with e xperimental hydrocephalus is due, at least in part, to calcium-activated pr oteolytic processes. This may have implications for supplemental drug treat ments of this disorder.