Striatal injection of 6-hydroxydopamine induces retrograde degeneration and glial activation in the nigrostriatal pathway

Abstract

PURPOSE: The effect of a highly selective 6-hydroxydopamine (6-OHDA)-induced lesion of the nigrostriatal system on the astroglial and microglial activation was analysed in adult Wistar rats after an unilateral striatal injection of the neurotoxin. METHODS: Male rats received an unilateral stereotaxical injection of the 6-OHDA in the left side of the neostriatum and were sacrificed 22 days later. Control animals received the injection of the solvent. The rotational behaviour was registered by a rotometer just before the sacrifice. Immunohistochemistry was employed for visualization of the tyrosine hydroxylase (TH) positive dopamine cells, glial fibrillary acidic protein (GFAP) immunolabeled astrocytes and OX42 immunoreactive microglia. Stereological method employing the optical disector was used to estimate the degree of the changes. RESULTS: The striatal injection of the 6-OHDA induced a massive disappearance (32% of control) of the TH immunoreactive terminals in a defined area within the striatum surrounding the injection site. A disappearance (54% of control) of dopamine cell bodies was observed in a small region of the ipsilateral pars compacta of the substantia nigra (SNc). The GFAP and OX42immunohistochemistry revealed astroglial and microglial reactions (increases in the number and size of the cells) in the ipsilateral neostriatum and SNc of the 6-OHDA injected rats. CONCLUSIONS: The striatal injection of 6-OHDA leads to retrograde degeneration as well as astroglial and microglial activation in the nigrostriatal dopamine pathway. Modulation of activated glial cells may be related to wound repair and to the trophic paracrine response in the lesioned nigrostriatal dopamine system.

The Treadmill Exercise Protects against Dopaminergic Neuron Loss and Brain Oxidative Stress in Parkinsonian Rats

“…The striatal injection of 6-OHDA was shown to lead to a massive disappearance of TH immunoreactive terminals, in a defined area within the striatum, surrounding the injection site [ 50 ]. TH is the rate-limiting enzyme for brain catecholamine synthesis, and reduction of TH expression results in diminished DA synthesis, leading to PD, what makes TH essential in the pathogenesis of PD [ 51 ].…”

Differential astroglial responses in the spinal cord of rats submitted to a sciatic nerve double crush treated with local injection of cultured Schwann cell suspension or lesioned spinal cord extract: implications on cell therapy for nerve repair

“…Likewise, astrocytes in the brain and spinal cord react after injury by changing their shape and by producing neurotrophic factors and immunoregulatory molecules 27 . Initial action is to promote wound and repair, by eliminating injured neurons and axons, and also restoring brain barriers 29 . Subsequent events are related to further protection of remaining neurons, fi ber growth and restoration of function 20 .…”

Computationally Guided Intracerebral Drug Delivery via Chronically Implanted Microdevices

“…A flowchart of COMMAND is shown in Figure S4, along with examples of stereotaxic coordinates used by prior studies in Figure S5 (Aoi et al, 2000;Bilang-Bleuel et al, 1997;Cederfjä ll et al, 2015;Hattori et al, 1998;Horellou et al, 1994;Kilbourn et al, 1997;Kirik et al, 2000;Luo et al, 1999;Mandel et al, 1998;Rodrigues et al, 2003;Sacaan et al, 1991;Shults et al, 1996;Wang et al, 2017aWang et al, , 2017bZaczek et al, 1980).…”