Enhanced Sensorimotor Functional Recovery and Neurovascular Regeneration after Stroke with Chronic Citalopram Treatment Público
Espinera, Alyssa Rae (2012)
Abstract
Abstract
Enhanced Sensorimotor Functional Recovery and Neurovascular
Regeneration after Stroke with
Chronic Citalopram Treatment
Recent clinical trials have reported that selective serotonin
reuptake inhibitor treatment after
stroke enhances motor functional recovery; however, the underlying
mechanisms need to be further
elucidated. We hypothesized that daily administration of citalopram
would enhance neurovascular repair
in the ischemic penumbra while accelerating sensorimotor functional
recovery. Focal ischemic stroke was
produced in male C57/B6 mice by ligation of the distal middle
cerebral artery and 7-minute occlusion of
the bilateral common carotid arteries. Citalopram (10mg/kg, i.p.)
was injected 24h after stroke and daily
thereafter. BrdU was injected daily to mark proliferating cells. An
adhesive removal task was used to
measure changes in forelimb sensorimotor function after stroke.
Immunohistochemical staining was used
to assess the presence of newly born neurons and vessels and to
illustrate neural migration. Citalopram
treatment did not reduce acute infarct volume (72h), but did
enhance functional recovery in the adhesive
removal behavior task after 14 days. Brain derived neurotrophic
factor expression was increased in the
peri-infarct region after 7 days of citalopram treatment. Migration
of proliferating cells was observed
between the sub-ventricular zone neural precursor niche and the
peri-infarct area in both control and
citalopram-treated mice; however, citalopram-treated animals had
more new neurons in the peri-infarct
region than did the control stroke animals in both 21 and 28d
treatment groups. Additionally, blood
vessel cross-sectional area in the peri-infarct region was greater
in the citalopram treatment groups. These
results suggest that citalopram promotes sensorimotor recovery from
stroke while augmenting
neurogenesis and total vessel area in the peri-infarct region after
stroke.
Table of Contents
TABLE OF CONTENTS
Terminology/Abbreviations……………………………………………..……....1
I.
Introduction……………………………………………..….....3
II.
Experimental
Procedures………………………………...…....5
a. Treatment Groups
b. Middle Cerebral Artery Occlusion
c. Citalopram Administration
d. BrdU Administration
e. Infarct Volume
f. Behavioral Assessment
g. Immunohistochemistry
h. Cell counting using design based stereology
i. Western Blot
j. Statistical Analysis
III.
Results and
Figures………………………………………..……12
a. Acute Citalopram administration does not attenuate infarct
volume
b. Citalopram after stroke significantly accelerates sensorimotor
functional
recovery
c. Citalopram increases new neurons in the peri-infarct
region
d. Citalopram enhances vessel representation in the peri-infarct
region
e. Citalopram induces BDNF expression in the peri-infarct
region
IV.
Discussion
………………...…………………………………..…18
V.
Limitations……………………………………………………….22
VI.
References…………………………………………………...…...24
VII.
Figures
a. Figure A: Treatment
Groups………………………………6
b. Figure 1: Infarct
Volume…………….................................13
c. Figure 2: Sensorimotor
Recovery…………………………14
About this Honors Thesis
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