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

 

Diserahkan: 21 Mei 2019/Diterima: 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). Status oksidatif otak, otot, hipokampus dan korpus kalosum (CC) degenerasi bahan putih yang dinilai. Hasil menunjukkan bahawa 2VO diubah suai yang disebabkan oleh tingkah laku seperti anziolisis jangka pendek yang boleh diterbalikkan dalam EPM (p <0.05). Analisis tisu otak menunjukkan 2VO yang diubah suai secara beransur-ansur mengubah status oksidatif otak (p> 0.05) dengan infark bererti, hipokampal CA1, CA3, DG dan CC degenerasi yang terdedah (p <0.05). Ini ditemui bersama dengan pembelajaran reruang dan defisit kefleksibelan (p <0.05). Kepentingan pHCA 100 mg./kg. meningkatkan pembelajaran reruang dan kekurangan kefleksibelan bertepatan dengan penurunan bermakna kelantangan infarksi, CA1, CA3 dan CC degenerasi (p <0.05). Kami menyimpulkan bahawa pHCA meningkatkan kesan terhadap pembelajaran reruang dan defisit kefleksibelan melibatkan perlindungan saraf terhadap kegagalan tenaga oligemik yang disebabkan kemerosotan bahan neuron dan kemerosotan zat putih dalam tikus CCH.

Kata kunci: Asid p-hidroksisinamik; hipoperfusi serebrum kronik; kefleksibelan pembelajaran; lorongan keliru air; oklusi arteri karotid dua hala biasa; pembelajaran reruang; 2VO diubah suai

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*Pengarang untuk surat-menyurat; email: fsciwyth@ku.ac.th

 

 

 

 

 

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