Blackwell Publishing, Ltd. Quinolinic acid lesions of the caudate putamen in the rat lead to a local increase of ciliary neurotrophic factor

When applied prior to excitotoxic lesions, ciliary neurotrophic factor (CNTF) has been shown to be neuroprotective. However, data concerning the endogenous CNTF content of the intact rat striatum are rare and have not until now been available for the quinolinic acid (QA)-lesioned striatum. Therefore, we investigated the CNTF content in the QA-lesioned rat striatum for at least 1 month using immunohistochemistry and Western blot analysis. In lesioned striata a neuronal loss was observed by Nissl staining and by a reduction of NeuN-immunoreactive cells, whereas increased glial fibrillary acidic protein immunoreactivity showed a gliotic reaction. With CNTF immunohistochemistry we found that in the QA-lesioned striatum CNTF was increased over time, whereas it was not detectable in intact and sham-lesioned striata. CNTF-immunoreactive cells had the morphology of protoplasmatic astrocytes. Furthermore, quantitative Western blotting demonstrated that the content of CNTF protein from striatal lysates containing 1 mg of whole protein 1 month after QA lesioning (2.76 ± 1.71 ng) was significantly increased ( P < 0.05, U -test) compared with sham-lesioned hemispheres (0.68 ± 0.25 ng) and intact controls (0.55 ± 0.25 ng). We conclude that CNTF content is correlated with glial scar formation and suggest that our results may be of relevance to cell grafting strategies for the treatment of Huntington’s disease.