Myelin development in young hydrocephalic rats
Zhang, Yi Wei
Hydrocephalus is a neurological disorder characterized by excessive cerebrospinal fluid (CSF) accumulation in enlarged ventricular cavities inside the brain. Hydrocephalus is associated with gradual progressive impairment and destruction of cerebral white matter. To investigate the potential for reversibility of these changes, hydrocephalus was induced in three week old rats by injection of kaolin into cisterna magna. Ventricle size was confirmed by MR imaging. Ultrastructural changes within the corpus callosum, the number of axons per unit area, and myelin thickness were assessed. Myelin proteolipid protein (PLP) and axon growth associated protein (GAP-43) were assayed in cerebrum by Northern blot and immunoblot. GAP-43 protein also was measured by immunohistochemistry. Axon transport function was detected by retrograde labeling of Fluoro-Gold tracer. At one week hydrocephalus, the myelin sheath around axons greater than 0.4$\mu$m diameter was abnormally thin, PLP protein was significantly reduced, axons per unit area were less, and GAP-43 protein was increased in the periventricular white matter. PLP and GAP-43 mRNAs were up-regulated. Axonal transport appeared to be normal in two week hydrocephalic rats. With persistent hydrocephalus at four weeks, axons were destroyed, and PLP protein decreased, however myelin sheath developed an appropriate thickness around existing axons, and GAP-43 protein remained elevated. Shunt treatment of hydrocephalus at one week prevented severe damage to axons and myelin. The PLP and GAP-43 mRNAs and proteins were maintained at intermediate levels between hydrocephalus and controls. These data suggest that early hydrocephalus delays myelination in young rat brains. Up-regulated mRNA of PLP suggests an attempt to increase synthesis of myelin protein and recover retarded myel nation. GAP-43 changes suggest that neurons rapidly respond to hydrocephalic injury and adjust their functional state to prepare for stress. In immature hydrocephalic rat brain, there is a potential to develop normal myelin sheaths if axons survive.