Medical Pharmacology Commons^™

Targeting The Endocannabinoid System To Reduce Inflammatory Pain, Sudeshna Ghosh

Theses and Dissertations

The endogenous cannabinoids (endocannabinoids) anandamide (AEA) and 2-arachidonylglycerol (2-AG) exert their effects predominantly through cannabinoid CB1 and CB2 receptors, but these actions are short-lived because of rapid hydrolysis by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. Selective inhibition of either enzyme elevates CNS levels of the appropriate endocannabinoid and produces analgesic effects with fewer psychomimetic side effects than Δ9-tetrahydrocannabinol (THC), the primary active constituent of marijuana. While cannabinoid receptor agonists and FAAH inhibitors reliably produce anti-inflammatory and anti-hyperalgesic effects in the carrageenan test and other inflammatory pain models, much less is known about the consequences of inhibiting …

Triterpenoid Modulation Of Il-17 And Nrf-2 Expression Ameliorates Neuroinflammation And Promotes Remyelination In Autoimmune Encephalomyelitis, Tej K. Pareek, Abdelmadjid Belkadi, Sashi Kesavapany, Anita Zaremba, Sook L. Loh, Lianhua Bai, Mark L. Cohen, Colin Meyer, Karen T. Liby, Robert H. Miller, Michael B. Sporn, John J. Letterio

Dartmouth Scholarship

Inflammatory cytokines and endogenous anti-oxidants are variables affecting disease progression in multiple sclerosis (MS). Here we demonstrate the dual capacity of triterpenoids to simultaneously repress production of IL-17 and other pro-inflammatory mediators while exerting neuroprotective effects directly through Nrf2-dependent induction of anti-oxidant genes. Derivatives of the natural triterpene oleanolic acid, namely CDDO-trifluoroethyl-amide (CDDO-TFEA), completely suppressed disease in a murine model of MS, experimental autoimmune encephalomyelitis (EAE), by inhibiting Th1 and Th17 mRNA and cytokine production. Encephalitogenic T cells recovered from treated mice were hypo-responsive to myelin antigen and failed to adoptively transfer the disease. Microarray analyses showed significant suppression of …

Targeting The Endocannabinoid System To Reduce Nociception, Lamont Booker

Theses and Dissertations

Pain of various etiologies (e.g., visceral, inflammatory) can be a debilitating disorder that presents a problem of clinical relevance. While it is known that ∆9-tetrahydrocannabinol (THC) the primary psychoactive constituent found in marijuana produces analgesia in various rodent models of pain, its pharmacological properties are overshadowed by its psychomimetic effects. THC is the primary phytocannabinoid found in marijuana though other prevalent constituents such as the phytocannabinoids (e.g., cannabidiol (CBD), cannabinol (CBN), cannabichromene (CBC), tetrahydrocannabivarin (THCV)) may possess antinociceptive actions without the psychomimetic effects associated with THC. Indeed, these phytocannabinoids act upon the endocannabinoid system (ECS) that is comprised of the …

Cannabinoid Receptor Type 2 Activation Induces A Microglial Anti-Inflammatory Phenotype And Reduces Migration Via Mkp Induction And Erk Dephosphorylation, Edgar A. Romero-Sandoval, Ryan Horvath, Russell P. Landry, Joyce A. Deleo

Dartmouth Scholarship

Cannabinoid receptor type 2 (CBR2) inhibits microglial reactivity through a molecular mechanism yet to be elucidated. We hypothesized that CBR2 activation induces an anti-inflammatory phenotype in microglia by inhibiting extracellular signal-regulated kinase (ERK) pathway, via mitogen-activated protein kinase-phosphatase (MKP) induction. MKPs regulate mitogen activated protein kinases, but their role in the modulation of microglial phenotype is not fully understood.

Immunomodulatory Effects Of Novel Therapies For Stroke, Aaron A. Hall

USF Tampa Graduate Theses and Dissertations

Each year, approximately 795,000 people suffer a new or recurrent stroke. About 610,000 of these are first attacks, and 185,000 are recurrent attacks (Carandang et al. 2006). Currently the only FDA approved treatment for ischemic stroke is recombinant tissue plasminogen activator (Alteplase) (Marler and Goldstein 2003). Unfortunately its use is restricted to a short, 4.5 hour, time window. Two promising therapies in the treatment of stroke at delayed timepoints are human umbilical cord blood cells (HUCBC) and the sigma receptor agonist DTG

The first series of experiments were conducted to characterize the effects of sigma receptors on various aspects of …

Alternative Targets For The Treatment Of Stroke, Craig T. Ajmo Jr.

USF Tampa Graduate Theses and Dissertations

Stroke is cerebrovascular injury that has been reported to be the third leading cause of death and the first leading cause of disability in the world (W. H.O. 2007). Currently, there is only one FDA approved treatment for stroke which is recombinant tissue plasminogen activator. This treatment has a narrow therapeutic window of three hours after ischemic stroke and can adversely cause the production of oxygen free radicals and intracranial hemorrhage. These limitations result in only 2-3% of all stroke victims as being candidates for this therapy as many patients do not arrive at the hospital in time to receive …