Areas of Interest
The research in our laboratory focuses on the cellular and
molecular mechanisms of central nervous system (CNS) injury
during stroke, in order that we may devise pharmacological
strategies to attenuate the cellular destruction that follows
loss of blood flow to the brain.
Thus, the work performed in our laboratory could be described
as translational as it is pre-clinical in nature.
Research Description
Specifically, we seek to elucidate the molecular and
biochemical mechanisms by which post-ischemic inflammation
contributes to the progression of the neuronal injury that
follows stroke. Studies have determined that the brain damage
associated with cerebral ischemia is mediated by
over-stimulation of excitatory amino acid receptors,
particularly of the NMDA subtype, as well as inflammatory
factors. While inflammatory cells from the periphery may
contribute to neuronal damage there is evidence that
inflammatory genes expressed in parenchymal cells of the CNS in
response to excitotoxic insults can also play a deleterious
role. Currently our work is focused on determining the extent to
which the activation of inducible forms of nitric oxide (NO)
synthase and cyclooxygenase (COX) contribute to the progression
of neurodegeneration that occurs after ischemic injury. Improved
definition of these events could lead to the development of new
therapeutic strategies designed to prevent the delayed
progression of neuronal injury that follows cerebral ischemia.
Conventional pharmacology and biochemistry, immunohistochemistry,
protein and nucleic acid analyses as well as light, fluorescent
and confocal microscopy are techniques in current use.
Publications
Selected Publications
Fogal B, Hewett SJ.Interleukin-1beta: a bridge between
inflammation and excitotoxicity? J Neurochem. 2008 Mar 19; [Epub
ahead of print] PMID: 18315560.
Hamby ME, Gragnolati AR, Hewett SJ, Hewett JA.TGFbeta1 and
TNFalpha potentiates nitric oxide production in astrocyte
cultures by recruiting distinct subpopulations of cells to
express NOS-2.Neurochem Int. 2008 May;52(6):962-71.
Hamby ME, Hewett JA, Hewett SJ.TGF-beta1 reduces the
heterogeneity of astrocytic cyclooxygenase-2 and nitric oxide
synthase-2 gene expression in a stimulus-independent manner.
Prostaglandins Other Lipid Mediat. 2008 Mar; 85(3-4):115-24.
Fogal B, Li J, Lobner D, McCullough LD, Hewett SJ. System
x(c)- activity and astrocytes are necessary for interleukin-1
beta-mediated hypoxic neuronal injury. J Neurosci. 2007 Sep
19;27(38):10094-105.
Hewett SJ, Silakova JM, Hewett JA. Oral treatment with
rofecoxib reduces hippocampal excitotoxic neurodegeneration.J
Pharmacol Exp Ther. 2006 Dec;319 (3):1219-24.
Hamby, ME, Hewett, SJ, and Hewett, JA. (2006) Purification of
primary astrocyte cultures: A rapid procedure for the removal of
microglia. J. Neurosci. Methods 150: 128-137.
Hamby, M.E., Hewett, J.A., Hewett, S.J. (2006) TGF-b1
potentiates astrocytic nitric oxide production by expanding the
population of astrocytes that express NOS-2. Glia 54(6):566-77.
Hewett, S.J., Bell, S.C. and Hewett, J.A. (2006)
Contributions of cyclooxygenase-2 to neuroplasticity and
neuropathology of the central nervous system. Pharmacology and
Therapeutics 112(2):335-57.
Hewett, S.J., Silakova, J.M., and Hewett, J.A. (2006) Oral
treatment with rofecoxib reduces hippocampal excitotoxic
neurodegeneration. J. Pharmacol and Exp Ther. 319(3):1219-24
Fogal B, Trettel J, Uliasz TF, Levine ES, Hewett SJ. (2005)
Changes in secondary glutamate release underlie the
developmental regulation of excitotoxic neuronal cell death.
Neuroscience. 132(4):929-42.
Fogal B, Hewett JA, Hewett SJ. (2005) Interleukin-1b
potentiates neuronal injury in a variety of injury models
involving energy deprivation. J Neuroimmunol. 161(1-2):93-100.
Vidwans, A.S., and Hewett, S.J. (2004) Enhanced synaptic
release of glutamate underlies the potentiation of
oxygen-glucose deprivation-induced neuronal injury after
induction of NOS-2. Exp Neurol. 190(1):91-101.
Silakova J.M., Hewett ,J.A., Hewett ,S.J. (2004) Naproxen
Reduces Excitotoxic Neurodegeneration In Vivo with an Extended
Therapeutic Window. J Pharmacol Exp Ther. 309(3):1060-6.
Church, W.H, and Hewett, S,J. (2003) Relationship between
NMDA receptor expression and MPP+ toxicity in cultured
dopaminergic cells. J Neurosci Res. 73(6):811-7. (photo on
journal cover)
 View more publications, see
Pubmed listing. |
