Is this enough for your stroke hospital to contact researchers and get human clinical trials done? OR WILL THEY DO NOTHING LIKE THEIR USUAL INCOMPETENCE?
Authors' Affiliations
Hannah M. Malone, Department of Biomedical Sciences, College of Medicine, East Tennessee State University, Johnson City, TN.
Dr. Cuihong Jia, Department of Biomedical Sciences, College of Medicine, East Tennessee State University, Johnson City, TN.
Dr. Theo Hagg, Department of Biomedical Sciences, College of Medicine, East Tennessee State University, Johnson City, TN.
Location
BEECH MTN. ROOM 120
Start Date
4-12-2019 10:20 AM
End Date
4-12-2019 10:35 AM
Name of Project's Faculty Sponsor
Dr. Theo Hagg
Type
Oral Presentation
Classification of First Author
Graduate Student-Doctoral
Project's Category
Healthcare and Medicine, Traumatic Brain Injury, Stroke
Abstract
Stroke increases neurogenesis (birth of new neurons) through
upregulation of ciliary neurotrophic factor (CNTF), a potent neurogenic
cytokine made almost exclusively in the central nervous system. Previous
study found that CNTF is induced and needed to stimulate neurogenesis
in the subventricular zone (SVZ) of mouse brain in a stroke model. CNTF
also has a neuroprotective function. Focal adhesion kinase (FAK),
protein tyrosine kinase 2, is ubiquitously expressed in various cell
types and mediates cell adhesion and migration. We previously discovered
that systemic inhibition of FAK upregulates CNTF expression in the SVZ,
making FAK a pharmacological target to increase CNTF to promote
neurogenesis and neuroprotection after stroke. This study examined
whether systemic FAK inhibitor treatment after stroke regulates SVZ
neurogenesis and neuroprotection using a middle cerebral artery
occlusion (MCAO) to induce a stroke in adult male C57BL/6 mice. A
filament was inserted in the external carotid artery and then fed
through the carotid bifurcation into the internal carotid artery to the
base of the middle cerebral artery. After 30 minutes of occlusion, the
filament was removed to restore blood flow. Mice were randomly assigned
to receive 3 daily doses of saline or FAK inhibitor (FAK14, i.p., 3
mg/kg) and treatment started at 6 hours, 12 days, or 58 days after MCAO.
Because CNTF has a neuroprotective function, the amount of tissue
damage was analyzed to compare treatment groups. The neuroprotective
role of FAK14 was examined by measuring MCAO-induced infarction. The
infarct size was measured using the absence of NeuN (neuronal cell
marker) and GFAP (activated astrocytes) and presence of CD68 (activated
microglia). FAK14 given at 6 hours post-stroke reduced the infarct size
to 38% of the uninjured side of the brain compared to 46% with saline.
Proliferating cells were labeled by injecting bromodeoxyuridine (BrdU,
50 mg/kg), the mice were processed 2 h after the last BrdU injection,
and proliferated cells in the SVZ were counted with unbiased stereology.
There were no significant differences in the total numbers of BrdU+
cells between saline and FAK14 at 3, 14 and 60 days. Future studies are
needed to confirm the levels of CNTF at the various times of treatment.
If there is no difference in CNTF expression or increased expression of
counteracting cytokines, no difference in neurogenesis between groups
would be expected. The neuroprotective effect of FAK14 during the acute
phase following injury could provide novel pharmacological options to
stroke patients extending the current therapeutic treatment window.
