Neuroprotective effects of meloxicam on transient brain ischemia in rats:the two faces of anti-inflammatory treatments

The inflammato ry response plays an important role in neuroprotection and regeneration after ischemic insult.The use of non-ste roidal 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 stro ke,but its ability to inhibit both cyclooxygenase isoforms(1 and 2) could be a promising strategy to modulate postischemic inflammation.This study analyzed the effect of meloxicam in a transient focal cerebral 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 meloxicam’s 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 stro ke and encourages the careful analysis of both the neuroprotective and the regenerative effects in preclinical studies.

Neuroprotection by salubrinal treatment in global cerebral ischemia

Most common cerebrovascular accidents （CVAs） result from the occlusion of a blood vessel and are called ischemic stroke. The interruption of the blood flow reduces the oxygen and glucose levels in the neural pareuchyma, which in turn decreases the energy of the cells and compromises their homeostasis. This condition has to be reverted for cell survival. One of the homeostatic processes impaired by cerebral ischemia is protein folding in the endoplasmic reticulum （ER） lumen where unfolded proteins are accumulated （Degracia and Monti, 2004）. This situation, known as ER stress, elicits the so called unfolded protein response （UPR）,

Combining anti-inflammatory and unfolding protein responses to fight stroke

This perspective shows an attempt to obtain synergy effects to fight ischemic stroke by combining agents acting on two different homeostatic mechanisms:inflammation and unfolded protein response (Anuncibay-Soto et al.,2018).Different pharmacological approaches have been assayed to alleviate cerebrovascular accident (stroke), which represents one of the most devastating diseases in the elderly.

Using organotypic hippocampal slice cultures to gain insight into mechanisms responsible for the neuroprotective effects of meloxicam: a role for gamma aminobutyric and endoplasmic reticulum stress

This perspective aims to put into context the recent article by Landucci et al.(2018)on mechanisms involved in the neuroprotective effects of meloxicam on an organotypic hippocampal slice cultures(OHSCs)model.In vitro cell cultures are the main method for studying large quantities of homogeneous cells in an isolated environment.Thus,the use of primary dissociated neuron,astrocyte,oligodendrocyte,microglia,or endothelial cell cultures has become a standard