INFLAMMATORY MARKERS IN NEUROPLASTICITY INDUCED BY LESION IN DIFFERENT DEVELOPMENTAL WINDOWS

Early CNS lesions induce rapid circuitry reorganization, related to functional recovery, whereas adults display slower, partial plasticity. Lesions induce neuroinflammation, promoting the study of the interplay between neuroplasticity and immune responses in CNS injury. TNF-α, a key proinflammatory cytokine, also can modulate neuroplasticity. Here we explore different interactions between microglia, astrocytes, and retinocollicular projections after monocular enucleation (ME) in distinct developmental stages. Also the role of TNF-α signaling in microglia-mediated plasticity after lesion. Lister Hooded rats submitted to ME at P10/ P21 were analyzed at different survival times. One group received minocycline or TNF-α neutralizing antibody treatment, both in enucleated animals at P10. RT-PCR evaluated inflammatory cytokines. Neuroanatomical tracers mapped structural plasticity. Immunofluorescence and western blot assessed glial and microglial reactivity, BDNF, TNFR and iNOS content. At P10, ME induces a persistent and robust sprout in the superior colliculus (SC) within 24 hours contrasting with a discreet intralaminar sprouting observed 7 days after injury in P21. Microglial contralateral reactivity 24h after ME in P10 pairs with axonal sprouting. It peaks at 72h, when GFAP is expressed beyond the border of SC. By day 7, glial reactivity normalized in P10, while in P21, glial and microglial activation persisted until day 14. An increase in TNFR1/2  after lesion in P21 was observed. Despite no immediate increase in BDNF or TNF-α mRNA 24h after lesion at P10, minocycline and TNF-α inhibition reduced axonal sprouting in 59.4%. At P21, sustained inflammation was evident through progressive increase of iNOS and NFκB levels, with TNF-α mRNA peaking 24h post-injury. In summary, distinct neuroimmune dynamics may underlie rapid and gradual neuroplastic changes across different stages of development with TNF-α  as a regulatory signalling.