The neuroprotective effects of co-ultraPEALut in a mouse model of spinal cord injury

Traumatic injuries to the spinal cord frequently cause permanent neurological disabilities and yet there is no effective therapeutic option to improve functional recovery. Spinal cord injury (SCI) is well-known to induce the formation of reactive astrocytes and the infiltration of immune cells in the area of the lesion site, but whether SCI also induces the production of new neurons in vivo remains controversial. Neurogenesis has been described in various regions of the central nervous system. Significant spontaneous neuroplasticity occurs over the weeks and months following brain or spinal cord trauma leading to some functional recovery. Moreover, studies have shown that spinal neurogenesis occurs to a limited extent after SCI, but that it could be stimulated by experimental intervention. In that regard, in a recent study, we have demonstrated that treatment with a new composite, a formulation including palmitoylethanolamide (PEA) and the antioxidant compound luteolin (Lut), subjected to an ultramicronization process, co-ultraPEALut, significantly reduced inflammatory secondary damage associated with SCI. Thus, the aim of this study was to investigate the neuroprotective effect of co-ultraPEALut in the injury-induced neurogenesis in a mouse model of SCI. SCI was induced in mice through spinal cord compression by the application of vascular clips (force of 24 g) to the dura via a four-level T5 to T8 laminectomy. The animals were sacrificed and the spinal cord were collected. Chronic exogenous administration of co-ultraPEALut increased bromodeoxyuridine (BrdU) and doublecortin immunoreactive cells in the spinal cord of SCI subjected mice. This neuronal development was correlated with synaptic plasticity, identified using the Golgi impregnation method to quantify dendritic spines in spinal cord. In addition, co-ultraPEALut treatment also increased the expression of different neurotrophic factors such as brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), nerve growth factor (NGF) and neurotrophin-3 (NT-3). The results indicate that co-ultraPEALut could have a role on birth, survival, and differentiation of new neurons and maturation of spines in the spinal cord and could be a therapeutic target in traumatic diseases.