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1) Gene
therapy is seen as especially promising for the treatment of
neurodegenerative disorders.
However, the immune system diminishes the effectiveness
of gene therapy in experimental models, possessing a highly
evolved response to virally infected cells.
Of particular importance is the innate immune response,
a cell-mediated viral defense mechanism which serves to
stimulate an acquired, T-cell mediated response.
With John Olschowka, Howard Federoff, and William
Bowers, we are looking a innate immune responses to viral
vectors within the brain and strategies for both ameliorating
the innate immune response and improving viral vectors within
the brain and strategies for both ameliorating the innate
immune response and improving viral vector delivery.
2) Human
herpesvirus 6 (HHV6) is a candidate virus for Multiple
Sclerosis, and has been shown to be involved in progressive
multifocal leukoencephalophathy, a demyelinating disorder
associated with immunosuppression. HHV6 has been shown to
infect human microglia and oligodendrocytes in culture.
With David Mock, Andrew Goodman, and John Olschowka, we
are looking at the effects of HHV6 infection on human glial
cells in vitro. Currently,
we are looking at cytokine and chemokines profiles of infected
human microglia, and we are looking at the transactivation
effects by different human herpesviruses on isolated human
oligodendrocytes.
3) The
enzymes cyclooxygenase-1 and -2 have been linked to a variety
of CNS processes – including brain inflammation and neuronal
activity. With
Kerry O' Banion we have been examining the distribution of
these enzymes in the post-mortem brains of persons with
schizophrenia, bipolar disorder and manic depression, with the
hypothesis that altered regulation of these enzymes might play
a role in the course of these psychological syndromes.
4) MPTP-induced degeneration of dopaminergic neurons
produces a robust microglial response.
Microglia, in acute models of brain injury, have been
shown to be both neurotoxic and neurotrophic.
With Kerry O'Banion and Suzanne Haber, we are engaged
in examining the microglial response to a low-dose treatment
with MPTP in monkeys.
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Hurley
,
S.D.
; Olschowka, J.A.; and O'Banion,
M.K. 2001, Cyclooxygenase Inhibition as a Strategy to
Ameliorate Brain Injury. Journal
of Neurotrauma, In press.
Streit,
W.J.;
Hurley
,
S.D.
; McGraw, T.S.; Semple-Rowland,
S.L. 2000, Comparative evaluation of cytokine profiles and
reactive gliosis supports a critical role for interleukin-6 in
neuron-glia signaling during regeneration. Journal of
Neuroscience Research, 61: 10-20.
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