Microsphere embolism-induced elevation of nerve growth factor level and appearance of nerve growth factor immunoreactivity in activated T-lymphocytesin the rat brain

Changes in nerve growth factor (NGF) level and type of cells producing NGF were investigated in the rat brain after sustained cerebral embolism. The N GF level was determined by a two-site enzyme immunoassay specific for NGF, The cerebral cortex, striatum, and hippocampus of the embolized hemisphere maximally contained 2.4-, 2.4-, and 1.7-times higher NGF levels than the co rresponding regions of the non-embolized hemisphere, A significant increase was transiently observed for 1 week in the cerebral cortex and striatum, w hereas the increase was longer lasting, at least of 4 weeks' duration, in t he hippocampus. To examine the localization of NGF-like immunoreactivity (N GF-LI), we used a newly developed anti-NGF peptide antiserum that specifica lly recognized a 30-kDa molecule(s) in the hippocampal extracts or in NGF c DNA-transfected cells, suggesting that the antibody predominantly reacted w ith the putative NGF precursor protein(s), NGF-LI, which was localized in n eurons of the normal or non-embolized hemisphere, was reduced, and on the e mbolized side new signals emerged in small non-neuronal cells having a roun d shape. These included cells with common leukocyte antigen CD45 and T-lymp hocyte antigen CD3, which did not appear in the normal or non-embolized hem isphere. NGF-LI and CD3 were colocalized in a substantial number of the cel ls, suggesting that some activated T-lymphocytes produce NGF for neuronal r egeneration after sustained cerebral embolism. (C) 1999 Wiley-Liss, Inc.