MORTARDUDE
12-18-2003, 03:22 PM
Gulf War BBB changes with DEET, PB, and permethrin
------------------------------------------------------------
J Toxicol Environ Health A. 2004 Jan;67(2):163-92.
Stress and combined exposure to low doses of pyridostigmine bromide,
deet, and
permethrin produce neurochemical and neuropathological alterations in
cerebral
cortex, hippocampus, and cerebellum.
Abdel-Rahman A, Abou-Donia S, El-Masry E, Shetty A, Abou-Donia M.
Department of Pharmacology and Cancer Biology, Duke University Medical
Center,
Durham, North Carolina, USA.
Exposure to a combination of stress and low doses of the chemicals
pyridostigmine bromide (PB), DEET, and permethrin in adult rats, a model
of Gulf
War exposure, produces blood-brain barrier (BBB) disruption and neuronal
cell
death in the cingulate cortex, dentate gyrus, thalamus, and
hypothalamus. In
this study, neuropathological alterations in other areas of the brain
where no
apparent BBB disruption was observed was studied following such
exposure.
Animals exposed to both stress and chemical exhibited decreased brain
acetylcholinesterase (AChE) activity in the midbrain, brainstem, and
cerebellum
and decreased m2 muscarinic acetylcholine (ACh) receptor ligand binding
in the
midbrain and cerebellum. These alterations were associated with
significant
neuronal cell death, reduced microtubule-associated protein (MAP-2)
expression,
and increased glial fibrillary acidic protein (GFAP) expression in the
cerebral
cortex and the hippocampal subfields CA1 and CA3. In the cerebellum, the
neurochemical alterations were associated with Purkinje cell loss and
increased
GFAP immunoreactivity in the white matter. However, animals subjected to
either
stress or chemicals alone did not show any of these changes in
comparison to
vehicle-treated controls. Collectively, these results suggest that
prolonged
exposure to a combination of stress and the chemicals PB, DEET, and
permethrin
can produce significant damage to the cerebral cortex, hippocampus, and
cerebellum, even in the absence of apparent BBB damage. As these areas
of the
brain are respectively important for the maintenance of motor and
sensory
functions, learning and memory, and gait and coordination of movements,
such
alterations could lead to many physiological, pharmacological, and
behavioral
abnormalities, particularly motor deficits and learning and memory
dysfunction.
PMID: 14675905 [PubMed ~ in process]
------------------------------------------------------------
J Toxicol Environ Health A. 2004 Jan;67(2):163-92.
Stress and combined exposure to low doses of pyridostigmine bromide,
deet, and
permethrin produce neurochemical and neuropathological alterations in
cerebral
cortex, hippocampus, and cerebellum.
Abdel-Rahman A, Abou-Donia S, El-Masry E, Shetty A, Abou-Donia M.
Department of Pharmacology and Cancer Biology, Duke University Medical
Center,
Durham, North Carolina, USA.
Exposure to a combination of stress and low doses of the chemicals
pyridostigmine bromide (PB), DEET, and permethrin in adult rats, a model
of Gulf
War exposure, produces blood-brain barrier (BBB) disruption and neuronal
cell
death in the cingulate cortex, dentate gyrus, thalamus, and
hypothalamus. In
this study, neuropathological alterations in other areas of the brain
where no
apparent BBB disruption was observed was studied following such
exposure.
Animals exposed to both stress and chemical exhibited decreased brain
acetylcholinesterase (AChE) activity in the midbrain, brainstem, and
cerebellum
and decreased m2 muscarinic acetylcholine (ACh) receptor ligand binding
in the
midbrain and cerebellum. These alterations were associated with
significant
neuronal cell death, reduced microtubule-associated protein (MAP-2)
expression,
and increased glial fibrillary acidic protein (GFAP) expression in the
cerebral
cortex and the hippocampal subfields CA1 and CA3. In the cerebellum, the
neurochemical alterations were associated with Purkinje cell loss and
increased
GFAP immunoreactivity in the white matter. However, animals subjected to
either
stress or chemicals alone did not show any of these changes in
comparison to
vehicle-treated controls. Collectively, these results suggest that
prolonged
exposure to a combination of stress and the chemicals PB, DEET, and
permethrin
can produce significant damage to the cerebral cortex, hippocampus, and
cerebellum, even in the absence of apparent BBB damage. As these areas
of the
brain are respectively important for the maintenance of motor and
sensory
functions, learning and memory, and gait and coordination of movements,
such
alterations could lead to many physiological, pharmacological, and
behavioral
abnormalities, particularly motor deficits and learning and memory
dysfunction.
PMID: 14675905 [PubMed ~ in process]