Enhanced Sensorimotor Functional Recovery and Neurovascular Regeneration after Stroke with Chronic Citalopram Treatment Open Access

Espinera, Alyssa Rae (2012)

Permanent URL: https://etd.library.emory.edu/concern/etds/9w0323994?locale=en
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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

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