| dc.description.abstracteng | Stroke is a major cause of death and disability in industrialized countries. Cortical plasticity is crucial for recovery and rehabilitation after a stroke. The aims of the study were to investigate the impact of a photothrombotically induced stroke (PT) in the primary somatosensory cortex (S1) on sensory learning and plasticity of the neighboring primary visual cortex (V1) in adult C57BL/6J mice. To challenge plasticity mechanisms, we used monocular deprivation (MD), a well-established model for experience-dependent plasticity in the visual system. Sensory learning, i.e. the increase of visual acuity and contrast sensitivity of the open eye after MD, was analyzed with a behavioral test, a virtual reality system based on the optomotor reflex. In addition, visual cortex activity and maps were recorded using intrinsic signal optical imaging in the same mice. In sham-operated control animals, MD induced a significant increase of visual abilities of the open eye and a significant ocular dominance (OD) shift towards this eye. In contrast, in lesioned animals, there was neither an increase in visual abilities nor an OD-shift in the lesioned hemisphere. Since the PT-lesion was located outside V1, the OD-plasticity in V1 must be affected by network influences. However, OD-plasticity was still present in the non-lesioned hemisphere. Since stroke is associated with inflammation, the therapeutic effect of the anti-inflammatory drug ibuprofen was tested: daily intraperitoneal injections of ibuprofen restored enhancement of vision but not OD-plasticity in the lesioned hemisphere. Consistent with this, a delay of 2 weeks between PT and MD also restored the enhancement of vision, but not OD-plasticity. Thus, inflammation was at least partly responsible for reductions in sensory learning in this paradigm, but lesion-induced impairment of OD-plasticity was mediated by a different cellular mechanism. We conclude that (i) both, sensory learning after PT and cortical plasticity in the surround of a cortical lesion are impaired; (ii) most likely a transient inflammation is responsible for impaired sensory learning, suggesting anti-inflammatory treatment with ibuprofen as a useful adjuvant therapy to support rehabilitation following stroke; and (iii) OD-plasticity cannot be just a local process and non-local influences are probably more important than previously assumed.
Moreover, we tested enriched environment (EE) housing as a non-invasive strategy to enhance plasticity in mice. OD-plasticity in mice is at its maximum at 4 weeks, declines in 2 to 3 months old animals and is absent beyond postnatal day (PD) 110 if mice are raised in standard cages (SC) (Lehmann & Löwel 2008). Since EE has been shown to promote plasticity mechanisms in the adult rodent brain (e.g. Sale et al. (2007)), we tested whether raising mice in EE could prolong the sensitive phase for OD-plasticity. To this end, we housed mice from 7 days before birth into adulthood (> PD 110) in EE, an age at which OD-plasticity is no longer present in SC-mice. Our results show that EE not only preserved OD-plasticity but created adult mice with juvenile-like OD-plasticity, even up to PD 196. Administration of diazepam to increase inhibition significantly reduced but did not completely abolish the EE–induced preservation of OD-plasticity into adulthood, indicating that the plasticity enhancing effect of EE was at least partly mediated by a reduced inhibitory tone. Using immunofluorescence, we found that the number of parvalbumin (PV)-positive labeled cells and WFA-positive labeled perineuronal nets (PNNs) in V1 were not changed by EE-housing. Furthermore, EE restored already lost plasticity: when SC-mice were transferred to EE at PD 110 (late EE), OD-plasticity was restored, even up to PD 320. To test whether EE might be used to prevent compromised plasticity after a photothrombotically induced stroke we again raised mice in EE and then exposed them to a stroke. Indeed, in adult EE-mice, OD-plasticity was present even after stroke and the improvement of visual abilities was partially preserved. Taken together, (i) EE preserved a juvenile-like OD-plasticity into late adulthood; (ii) which partially depended on inhibition. Moreover, EE-housing also (ii) restored OD-plasticity in SC raised animals and (iii) raising mice in an EE preserved OD-plasticity even after a PT-stroke. | de |