Transient and widespread astroglial activation in the brain after a striatal 6-OHDA-induced partial lesion of the nigrostriatal system.

The authors have previously described astroglial activation in the ipsilateral nigrostriatal system and ventral tegmental area following small doses of 6-hydroxydopamine (6-OHDA) injected unilaterally in the striatum. This article further evaluated astroglial reactivity in several brain regions after striatal 6-OHDA-induced punctate lesion in the nigrostriatal pathway. Adult male Wistar rats received a unilateral stereotaxical injection of the 6-OHDA (8 microg/4 microl) in the neostriatum and sacrificed 1 or 3 weeks later. Control animals received only solvent. Immunohistochemistry was employed for visualization of the tyrosine hydroxylase (TH), marker for dopamine cells, and glial fibrillary acidic protein (GFAP), marker for astrocytes. TH immunoreactive terminals disappeared in the striatum close to the injection site and a disappearance of a small number of a defined population of dopamine cell bodies was observed in the ipsilateral pars compacta of the substantia nigra (SNc). No dopamine lesion was detected in the contralateral nigrostriatal pathway. Astroglial reaction was seen close to the lesion in the neostriatum and in the ipsilateral SNc of the 1 week 6-OHDA lesioned rats. Specific stereological tools employing point intercepts and rotator, revealed an increased presence of reactive astrocytes in many forebrain regions like frontal, parietal and piriform cortex, septum, neostriatum and SNc, bilaterally, and also corpus callosum after 1 week of 6-OHDA injection. The astroglial activation was characterized by increases in the size of the cell body and/or processes. Astrocytic reaction was found only in the ipsilateral nigrostriatal pathway by 3 weeks of 6-OHDA, a slight activation also remaining in the ipsilateral septum and piriform cortex. Astrocytic reaction was seen in the solvent-injected rats only in the neostriatum close to the needle track. The transient widespread astroglial reaction observed in many brain regions following a striatal injection of 6-OHDA may represent a global paracrine trophic response in the brain.