The neuroprotective effect of meloxicam in a transient ischemia model involves an increase in axonal sprouting but a decrease in new neuron formation after 7 days ofreperfusion

Ugidos, I. F.; Gonzalez-Rodriguez, P.; Santos-Galdiano, M.; Font-Belmonte, E.; Anuncibay-Soto, B.; Perez-Rodriguez, D.; Fernandez-Lopez, A.

doi:10.1101/2021.04.05.438505

bioRxiv · 10.1101/2021.04.05.438505

The neuroprotective effect of meloxicam in a transient ischemia model involves an increase in axonal sprouting but a decrease in new neuron formation after 7 days ofreperfusion

Ugidos, I. F.·Gonzalez-Rodriguez, P.·Santos-Galdiano, M.·Font-Belmonte, E.·Anuncibay-Soto, B.·Perez-Rodriguez, D.·Fernandez-Lopez, A.

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Abstract

The inflammatory response plays an important role in neuroprotection and regeneration after ischemic insult. The use of non-steroidal anti-inflammatory drugs has been a matter of debate as to whether they have beneficial or detrimental effects. In this context, the effects of the anti-inflammatory agent meloxicam have been scarcely documented after stroke, but its ability to inhibit both cyclooxygenase isoforms (1 and 2) could be a promising strategy to modulate post-ischemic inflammation. This study analyzed the effect of the anti-inflammatory agent meloxicam in a transient focal ischemia model in rats, measuring its neuroprotective effect after 48 hours and 7 days of reperfusion and the effects of the treatment on the glial scar and regenerative events such as the generation of new progenitors in the subventricular zone and axonal sprouting at the edge of the damaged area. We show that meloxicams neuroprotective effects remained after 7 days of reperfusion even if its administration was restricted to the two first days after ischemia. Moreover, meloxicam treatment modulated glial scar reactivity, which matched with an increase in axonal sprouting. However, this treatment decreased the formation of neuronal progenitor cells. This study discusses the dual role of anti-inflammatory treatments after stroke and encourages the careful analysis of both the neuroprotective and the regenerative effects in preclinical studies. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/438505v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@1179ab9org.highwire.dtl.DTLVardef@af22b7org.highwire.dtl.DTLVardef@1025f6org.highwire.dtl.DTLVardef@2c4e06_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Ugidos, I. F., Gonzalez-Rodriguez, P., Santos-Galdiano, M., Font-Belmonte, E., Anuncibay-Soto, B., Perez-Rodriguez, D., Fernandez-Lopez, A.. 2021-04-06. The neuroprotective effect of meloxicam in a transient ischemia model involves an increase in axonal sprouting but a decrease in new neuron formation after 7 days ofreperfusion. https://doi.org/10.1101/2021.04.05.438505

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