Choroid plexus recovery after transient forebrain ischemia: Role of growthfactors and other repair mechanisms

1. Transient forebrain ischemia in adult rats, induced by 10 min of bilater al carotid occlusion and an arterial hypotension of 40 mmHg, caused substan tial damage not only to CA-1 neurons in hippocampus but also to epithelial cells in lateral ventricle choroid plexus. 2 When transient forebrain ischemia was followed by reperfusion (recovery) intervals of 0 to 12 hr, there was moderate to severe damage to many frond regions of the choroidal epithelium. In some areas, epithelial debris was s loughed into cerebrospinal fluid (CSF). Although some epithelial cells were disrupted and necrotic, their neighbors exhibited normal morphology. This patchy response to ischemia was probably due to regional differences in rep erfusion or cellular metabolism. 3. Between 12 and 24 hr postischemia, there was marked restoration of the N a+, K+, water content, and ultrastructure of the choroid plexus epithelium. Since there was no microscopical evidence for mitosis, we postulate that h ealthy epithelial cells either were compressed together on the villus or mi grated from the choroid plexus stalk to more distal regions, in order to "f ill in gaps" along the basal lamina caused by necrotic epithelial cell disi ntegration. 4. Epithelial cells of mammalian choroid plexus synthesize and secrete many growth factors and other peptides that are of trophic benefit following in jury to regions of the cerebroventricular system. For example, several grow th factors are upregulated in choroid plexus after ischemic and traumatic i nsults to the central nervous system. 5. The presence of numerous types of growth factor receptors in choroid ple xus allows growth factor mediation of recovery processes by autocrine and p aracrine mechanisms. 6. The capability of choroid plexus after acute ischemia to recover its bar rier and CSF formation functions is an important factor in stabilizing brai n fluid balance. 7. Moreover, growth factors secreted by choroid plexus into CSF are distrib uted by diffusion and convection into brain tissue near the ventricular sys tem, e.g., hippocampus. By this endocrine-like mechanism, growth factors ar e conveyed throughout the choroid plexus-CSF-brain nexus and can consequent ly promote repair of ischemia-damaged tissue in the ventricular wall and un derlying brain.