title: Granulocyte colony stimulating factor neuroprotective effects on spinal motoneurons after ventral root avulsion.
abstract: G-CSF is a glycoprotein commonly used to treat neutropenia. Recent studies have shown that the G-CSF receptor (G-CSF-R) is expressed by neurons in the central nervous system (CNS), and neuroprotective effects of G-CSF have been observed. In this study, the influence of G-CSF treatment on the glial reactivity and synaptic plasticity of spinal motoneurons in rats subjected to ventral root avulsion (VRA) was investigated. Lewis rats (7 weeks old) were subjected to unilateral VRA and divided into two groups: G-CSF and placebo treated. The drug treated animals were injected subcutaneously with 200 μg/kg/day of G-CSF for 5 days post lesion. The placebo group received saline buffer. After 2 weeks, both groups were sacrificed and their lumbar intumescences processed for transmission electron microscopy (TEM), motoneuron counting, and immunohistochemistry with antibodies against GFAP, Iba-1, and synaptophysin. Furthermore, in vitro analysis was carried out, using newborn cortical derived astrocytes. The results indicated increased neuronal survival in the G-CSF treated group coupled with synaptic preservation. TEM analyses revealed an improved preservation of the synaptic covering in treated animals. Additionally, the drug treated group showed an increase in astroglial reactivity both in vivo and in vitro. The astrocytes also presented an increased cell proliferation rate when compared with the controls after 3 days of culturing. In conclusion, the present results suggest that G-CSF has an influence on the stability of presynaptic terminals in the spinal cord as well as on the astroglial reaction, indicating a possible neuroprotective action.
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil. camilafreria@yahoo.com
authors.forename: Camila Marques
authors.initials: CM
authors.lastname: De Freria
authors.forename: Roberta
authors.initials: R
authors.lastname: Barbizan
authors.forename: Alexandre Leite Rodrigues
authors.initials: AL
authors.lastname: De Oliveira
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000502:physiology*; D009046:Motor Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D061251:Primary Cell Culture; D051381:Rats; D011917:Rats, Inbred Lew; D019051:Rhizotomy / Q000009:adverse effects; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013126:Spinal Nerve Roots / Q000187:drug effects* / Q000473:pathology / Q000502:physiology
chemical_list: D018696:Neuroprotective Agents; D016179:Granulocyte Colony-Stimulating Factor