Dr. Abdullah Ahmad

Use of Preclinical Models in Pursuit of a Cure for Ischemic Stroke

Dr. Abdulla Ahmad

Assistant Professor; Anesthesiology
Member, CTRND
Training
Post Doc, ACCM-Neuroscience, Johns Hopkins University, 2003-2010
Post Doc, Neuroscience-Toxicology, Hamdard University, India, 2002-2003
Ph.D., Chemistry, Aligarh Muslim University, India, 2001
M.S., Chemistry (Analytical), Aligarh Muslim University, India, 1996
B.S. (Honors), Chemistry, Zoology, Botany, Aligarh Muslim University, India, 1994

 
 
 

Contact Dr. Ahmad
Office: 352-294-5107
Lab: 352-294-5108
email:aahmad@anest.ufl.edu

Research Focus and Aims
Cyclooxygenase (COX) is the rate-limiting enzyme for the conversion of arachidonic acid to prostaglandin (PG) E2 (PGE2), PGD2, PGF2α, PGI2, and thromboxane A2 (TxA2), collectively known as prostanoids. COX and PGs are commonly perceived to be pro-inflammatory mediators. The prostaglandins play diverse roles in cell activity through their G-protein-coupled receptors (GPCR). The non-steroidal anti-inflammatory drugs (NSAID) have been widely used to inhibit COX-induced inflammation. By inhibiting COX, the NSAIDs also inhibit the PGs, which play a vital role in cellular physiology and pathophysiology. Thus the entire process compromises cellular homeostasis.

Current project:
One of the important PGs is PGD2. Interestingly it is the most abundant PG in the brain. PGD2 is generated from PGH2 by the action of two distinct PGD synthases. PGD2 has both peripheral and central physiologic effects. PGD2 exerts its effects through DP1 and DP2, also known as t-helper-type-2 (Th2) cell (CRTH2), receptors. Most of the PGD2 activity is regulated by DP1. By using a genetic and pharmacologic approach, we are determining the role of PGD2 in stroke. By using DP1 agonist, antagonist, and DP1-/- mice we are determining the role of DP1 in blood flow. Because “brain attack” is an acute process and usually happens without any warnings, scientists are encouraged to find therapeutic intervention(s) that could limit the brain damage after the attack. Therefore, we are also determining if the use of DP1 selective agonist after stroke can extend the therapeutic window such that the treatment could be provided several hours after the onset. Different strategies are being tested to extend the therapeutic window. We are also trying to determine if the proposed neuroprotection by using DP1 selective agonist is by regulating blood flow and vasculature, or does it have a direct neuronal effect mediated by intracellular mechanisms, or a combination of both. We are also correlating the anatomical outcome with behavioral outcomes. (Funding source: American Heart Association)

Recent Publications

  • Ahmad AS, Zhuang H, Doré S. Stimulation of prostaglandin EP2 receptors prevents NMDA-induced excitotoxicity. J Neurotrauma. 2006; 23:1895-1903.
  • Saleem S, Ahmad M, Ahmad AS, Yousuf S, Ansari MA, Khan MB, Ishrat T, Islam F. Behavioral and histologic neuroprotection of aqueous garlic extract after reversible focal cerebral ischemia. J Med Food. 2006; 9:537-544.
  • *Ahmad M, *Ahmad AS, Zhuang H, Maruyama T, Narumiya S, Doré S. Stimulation of prostaglandin E(2)-EP3 receptors exacerbates stroke and excitotoxic injury. J Neuroimmunol. 2007; 184:172-179.
  • Yousuf S, Atif F, Hoda N, Ahmad M, Saleem S, Ishrat T, Khan MB, Ahmad AS, Islam F. Oral supplementation of majun baladar ameliorates antioxidant enzyme activities in cerebral ischaemic damage. Basic Clin Pharmacol Toxicol. 2007; 101:246-253.
  • Ahmad AS*, Kim YT*, Ahmad M, Maruyama T, and Doré S. Selective blockade of PGE2 EP1 receptor protects brain against experimental ischemia and excitotoxicity, and hippocampal slice cultures against oxygen glucose deprivation. Neurotox. Res. 2008; 14:343-51.
  • Saleem S*, Ahmad AS*, Maruyama T, Narumiya S, Doré S. PGF FP receptors contribute to brain damage following transient focal brain ischemia. Neurotox. Res. 2008; 15:62-70.
  • Sen N, Hara MR, Ahmad AS, Cascio MB, Kamiya A, Ehmsen JT, Aggrawal N, Hester L, Dore S, Snyder SH, and Sawa A. GOSPEL: A novel neuroprotective protein that binds to GAPDH upon S-nitrosylation. Neuron 2009; 63:81-91.
  • Kang BN, Ahmad AS, Saleem S, Patterson R, Hester L, Doré S and Snyder SH. Death-associated Protein Kinase Mediated Cell Death Modulated by Interaction with DANGER. J Neurosci 2010; 30:93-98.
  • Mustafa AK, Ahmad AS, Zeynalov E, Gazi SK, Sikka S, Ehmsen JT, Barrow RK, Coyle JT, Snyder SH and Doré S. Serine Racemase Deletion Protects Against Cerebral Ischemia And Excitotoxicity. J Neurosci 2010; 30:1413-1416.
  • Ahmad AS*, Ahmad M*, Maruyama T, Narumiya S, and Doré S. Prostaglandin D2 DP1 receptor activation is beneficial in ischemic stroke and in acute excitoxicity in young and old mice. AGE 2010; 32:271-282.
  • Shah ZA, Li R, Ahmad AS, Kensler TW, Yamamoto M, Biswal S and Doré S. The flavanol (–)-epicatechin prevents stroke damage through the Nrf2-HO1 pathway. JCBFM 2010; 30:1951-61.
  • Lopez PHH, Ahmad AS, Mehta NR, Toner M, Rowland EA, Zhang J, Dore S and Schnaar RL. Myelin associated glycoprotein protects neurons from excitotoxicity. J Neurochem 2011; 116:900-8.

Link To PubMed