No abstract

In recent years, compelling evidence suggests that inflammation plays a critical role in the pathology of a vast number of neurological diseases such as stroke, Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis as well as neuropsychiatric diseases such as major depression and schizophrenia. Despite emerging evidence in human and animal models alike, modulating inflammatory responses have yet to be proven as an effective treatment to prevent or delay the progression of these diseases. The primary focus of this special edition is to highlight some of our current findings on the complexities of targeting neuroinflammation as a novel therapy, and its role in neurological and psychiatric disorders.

This commentary describes the significance of faculty citizenship in the broader context of institutional culture and defines faculty citizenship for use across all aspects of faculty roles in the Academy. The definition includes two key components (engagement and collegiality) that can be used to measure citizenship behaviors. Continued discussion and study of faculty citizenship will further the Academy's understanding and use of the concept.

Stroke is a devastating neurological event with limited treatment opportunities. Recent advances in understanding the underlying pathogenesis of cerebral ischemia support the involvement of multiple biochemical pathways in the development of the ischemic damage. Fenamates are classical non-steroidal anti-inflammatory drugs but they are also highly subunit-selective modulators of GABAA receptors, activators of IKS potassium channels and antagonists of non-selective cation channels and the NLRP3 inflammosome. In the present study we investigated the effect of mefenamic acid (MFA) in a rodent model of ischemic stroke and then addressed the underlying pharmacological mechanisms in vitro for its actions in vivo. The efficacy of MFA in reducing ischemic damage was evaluated in adult male Wistar rats subjected to a 2-h middle cerebral artery occlusion. Intracerebroventricular (ICV) infusion of MFA (0.5 or 1 mg/kg) for 24 h, significantly reduced the infarct volume and the total ischemic brain damage. In vitro, the fenamates, MFA, meclofenamic acid, niflumic acid, and flufenamic acid each reduced glutamate-evoked excitotoxicity in cultured embryonic rat hippocampal neurons supporting the idea that this is a drug class action. In contrast the non-fenamate NSAIDs, ibuprofen and indomethacin did not reduce excitotoxicity in vitro indicating that neuroprotection by MFA was not dependent upon anti-inflammatory actions. Co-application of MFA (100 μM) with either of the GABAA antagonists picrotoxin (100 μM) or bicuculline (10 μM) or the potassium channel blocker tetraethylammonium (30 mM) did not prevent neuroprotection with MFA, suggesting that the actions of MFA also do not depend on GABAA receptor modulation or potassium channel activation. These new findings indicate that fenamates may be valuable in the adjunctive treatment of ischemic stroke.

Non-steroidal anti-inflammatory drugs (NSAIDs) have been used extensively in the treatment of inflammatory disorders and pain. In recent years, emerging data suggest that some NSAIDs possess pharmacological properties, in addition to cyclooxygenase inhibition, which may be beneficial in the treatment of several neurological conditions. For example, fenamate NSAIDs potentiate GABA-A receptor function, indomethacin scavenges nitric oxide free radicals, and acetylsalicylic acid inhibits the translocation of NF-κB, all of which may contribute to their neuroprotective actions in selected experimental models of stroke. The purpose of this review is to explore the diverse pharmacological properties of NSAIDs in relation to their potential value in the treatment of selected neurological diseases.