Secondary Pathology of the Thalamus after Focal Cortical Stroke in Rats isnot Associated with Thermal or Mechanical Hypersensitivity and is Not Alleviated byIntra-Thalamic Post-Stroke Delivery of Recombinant CDNF or MANF

摘要

A stroke affecting the somatosensory pathway can trigger central post-stroke pain syndrome (CPSP). The symptoms often include hyperalgesia, which has also been described in rodents after the direct damage of the thalamus. Previous studies have shown that hemorrhagic stroke or ischemia caused by vasoconstriction in the thalamus induces increased pain sensitivity. We investigated whether inducing secondary damage in the thalamus by a cortical stroke causes similar pain hypersensitivity as has previously been reported with direct ischemic injury. We induced a focal cortical ischemia-reperfusion injury in male rats, quantified the amount of secondary neurodegeneration in the thalamus, and measured whether the thalamic neurodegeneration is associated with thermal or mechanical hypersensitivity. After one month, we observed extensive neuronal degeneration and found approximately 40% decrease in the number of NeuN+ cells in the ipsilateral thalamus. At the same time, there was a massive accumulation—a 30-fold increase—of phagocytic cells in the ipsilateral thalamus. However, despite the evident damage in the thalamus, we did not observe thermal or mechanical sensitization. Thus, thalamic neurodegeneration after cortical ischemia-reperfusion does not induce CPSP-like symptoms in rats, and these results suggest that direct ischemic damage is needed for CPSP induction. Despite not observing hyperalgesia, we investigated whether administration ofcerebral dopamine neurotrophic factor (CDNF) and mesencephalic astrocyte-derivedneurotrophic factor (MANF) into the ipsilateral thalamus would reduce the secondarydamage. We gave a single injection (10 µg) of recombinant CDNF or MANF protein into thethalamus at 7 days post-stroke. Both CDNF and MANF treatment promoted the functionalrecovery but had no effect on the neuronal loss or the amount of phagocytic cells in thethalamus.