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Sains Malaysiana 48(12)(2019): 2623–2631
http://dx.doi.org/10.17576/jsm-2019-4812-03
The
Effects of P-Hydroxycinnamic Acid in Ameliorating Spatial Learning and
Flexibility Deficits in Rats with Chronic Cerebral Hypoperfusion
(Kesan Asid P-Hidroksisinamik dalam Meningkatkan Pembelajaran Reruang
dan Defisit Kefleksibelan pada Tikus dengan Hipoperfusi Serebrum
Kronik)
NATSUDA MANYAGASA
& WACHIRYAH THONG-ASA*
Animal
Toxicology and Physiology Specialty Research Unit (ATPSRU), Physiology
Division, Department of Zoology, Faculty of Science, Kasetsart University, Bangkok
10900, Thailand
Received: 21
May 2019/Accepted: 26 September 2019
ABSTRACT
Cerebral blood reduction resulting in oligemic energy failure and
metabolic insufficiency initiates gradual neurodegeneration and
cognitive impairments. We investigated the neuroprotective effects
of p-hydroxycinnamic acid (pHCA) on neurodegeneration in association
with cognitive impairments in rats with chronic cerebral hypoperfusion
(CCH). Forty male Sprague-Dawley rats
were randomly divided into 4 groups: Sham-veh, 2VO-veh, 2VO-pHCA50
and 2VO-pHCA100. We used modified 2-vessel occlusion (2VO)
to induce CCH,
and the 2 latter groups were given 50 mg/kg and 100 mg/kg of pHCA
after the 2VO operation, respectively, which continued for 3 weeks.
The behavioral tests consisted of anxiety-like behavior tested in
an elevated plus maze (EPM)
and hippocampal-dependent spatial learning and flexibility tested
in a Morris water maze (MWM). Brain oxidative status, infarction, vulnerable hippocampus
and corpus callosum (CC) white matter degeneration
were evaluated. The results showed that modified 2VO induced reversible
short-term anxiolytic-like behavior in the EPM (p
< 0.05). Brain tissue analysis showed that modified 2VO induced
gradual change to brain oxidative status (p > 0.05) with significance
infarction, vulnerable hippocampal CA1, CA3, DG and CC degeneration
(p < 0.05). These were found along with significant spatial learning
and flexibility deficits (p < 0.05). Additionally, 100 mg/kg
of pHCA significantly ameliorated the spatial learning and flexibility
deficits, which coincided with the significant decreases of infarction
volume, CA1, CA3 and CC
degeneration (p < 0.05). We conclude that pHCA's
improving effects on spatial learning and flexibility deficits are
neuroprotective against oligemic energy failure-induced vulnerable
neuronal and white matter degeneration in CCH
rats. Keywords: Bilateral common carotid artery occlusion; chronic
cerebral hypoperfusion; learning flexibility; modified 2VO; p-hydroxycinnamic
acid; spatial learning; water maze
ABSTRAK
Pengurangan darah serebrum yang mengakibatkan kegagalan tenaga oligemik
dan kekurangan metabolik merupakan permulaan neurodegenerasi saraf
secara beransur-ansur dan merupakan masalah kognitif. Kami mengkaji
kesan neuropelindung asid p-hidroksisinamik (pHCA)
pada degenerasi saraf yang berkaitan dengan masalah kognitif pada
tikus hypoperfusion cerebral kronik (CCH). Tikus Sprague-Dawley jantan
empat puluh ekor secara rawak dibahagikan kepada 4 kelompok, iaitu
Sham-veh, 2VO-veh, 2VO-pHCA50 dan 2VO-pHCA100. Kami
menggunakan modul dua haluan kapal (2VO) untuk induksi CCH,
dan kedua-dua kelompok terakhir diberikan pHCA 50 mg./kg.
dan 100 mg./kg. selepas 2VO beroperasi dan berterusan selama 3 minggu.
Ujian tingkah laku terdiri daripada tingkah laku seperti kecemasan
dalam lorongan keliru atas terbaik (EPM) dan pembelajaran spatial yang bergantung pada hipokampal
dan kefleksibelan dalam lorongan keliru air Morris (MWM).
Kata kunci: Asid p-hidroksisinamik; hipoperfusi serebrum kronik; kefleksibelan pembelajaran; lorongan keliru air; oklusi arteri karotid dua hala
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*Corresponding
author; email: fsciwyth@ku.ac.th
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