Browsing by Subject "Microglia activation"

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    Systemic inflammation aggravates retinal ganglion cell vulnerability to optic nerve trauma in adult rats
    (MDPI, 2026-02-03) Rovere, Giuseppe ; Caja Matas, Yolanda; Vidal Villegas, Beatriz; Bernal Garro, José M. ; Sobrado Calvo, Paloma; Salinas Navarro, Manuel Ángel; Nucci, Carlo; Villegas Pérez, Maria Paz; Vidal Sanz, Manuel; Agudo Barriuso, Marta; Nadal-Nicolás, Francisco Manuel; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultades de la UMU::Facultad de Medicina
    Systemic inflammation is increasingly recognized as a modifier of neurodegenerative outcomes in the central nervous system; however, its impact on retinal ganglion cell (RGC) survival and retinal microglial responses following optic nerve (ON) injury in vivo remains incompletely understood. In this study, we investigated how systemic lipopolysaccharide (LPS)-induced inflammation influences retinal microglial activation and RGC vulnerability under physiological conditions and after traumatic ON damage. In adult female rats, systemic LPS administration by intraperitoneal injection induced rapid and robust microglial activation, characterized by process retraction and soma hypertrophy within hours and promoting microglial proliferation at later stages but without causing RGC loss in intact retinas. Following ON crush, systemic inflammation did not affect early RGC degeneration but significantly exacerbated neuronal loss during the late acute phase. This increased vulnerability was accompanied by a marked rise in microglial density and a pronounced redistribution of microglia toward the central retina and the ON head, a region of heightened anatomical and metabolic susceptibility. Together, these findings demonstrate that, in rats, systemic inflammation alone is insufficient to induce RGC degeneration but acts as a potent priming factor that amplifies neurodegeneration in the context of axonal injury. The temporal and spatial specificity of microglial responses underscores their context-dependent role in retinal pathology and identifies systemic inflammatory status as a critical determinant of retinal outcome after trauma. Targeted, time-dependent modulation of microglial activation may therefore represent a promising therapeutic strategy for optic neuropathies.
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    Upregulation of TLR9 may contribute to activation of microglia and painful diabetic neuropathy via the p38 MAPK pathway in rats
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Niu, Zhaoxia; Bao, Lei; Chen, Jing
    Painful diabetic neuropathy is a common chronic complication of diabetes, and the underlying mechanism remains largely elusive. A rat model of painful diabetic neuropathy was established via streptozotocin (STZ) injection and assessed as increased heat and mechanical hypersensitivity. An upregulation of TLR9 was observed in the spinal cords of rats injected with STZ and rat microglia (primary microglia and immortalized microglia HAPI) treated with high glucose. To investigate the role of TLR9 in high glucoseinduced microglia activation, short hairpin RNAs targeting TLR9 were used in vitro to knock down TLR9 in HAPI cells. TLR9 interference suppressed the high glucose-induced expression and secretion of inflammatory cytokines (TNF-α, IL-1β, and IL-6), IBA1 expression and the chemotaxis of HAPI microglia. Similar results were obtained when HAPI microglia were incubated with a p38 inhibitor (SB203580). P38 and ERK were downstream of TLR9 because TLR9 ablation markedly inhibited the phosphorylation of p38 and ERK. TLR9 was also knocked down in vivo via the injection of shTLR9 lentiviral vector into the rat spinal cord. Relief of STZ-induced heat and mechanical hypersensitivity was observed in rats with TLR9 interference, and TLR9 knockdown prevented STZinduced inflammatory cytokine secretion and microglial and MAPK signaling activation. Our study revealed the participation of TLR9 in microglial activation and diabetes-induced hyperalgesia likely via the MAPK pathway. The targeting of TLR9 may be an effective strategy for the treatment of painful diabetic neuropathy.