Sains Malaysiana 49(2)(2020): 375-382

http://dx.doi.org/10.17576/jsm-2020-4902-15

The Effect of Intranasal Administration of ACTH Analogue Toward Neural Progenitor/Stem Cells Proliferation after Traumatic Brain Injury

(Kesan Administrasi Intranasal Analog ACTH terhadap Proliferasi Neural Progenitor/Sel Stem selepas Kecederaan Trauma Otak)

MICHAEL LUMINTANG LOE¹*, RR. SUZY INDHARTY¹, ANDRE MP SIAHAAN¹, STEVEN TANDEAN¹ & WIBI RIAWAN²

¹Department of Neurosurgery, Faculty of Medicine, Universitas Sumatera Utara/Haji Adam Malik General Hospital, Medan 20155, Indonesia

²Department of Biochemistry, Faculty of Medicine, University of Brawijaya, Malang 65145, Indonesia

Received: 7 September 2019/Accepted: 24 October 2019

ABSTRACT

Traumatic brain injury (TBI) is a major health problem because of its high mortality and long-term disability worldwide. Neural progenitor/stem cells (NPSCs) that survive in certain parts of the brain, enable brain to produce new neurons and glia. ACTH_4-10Pro⁸-Gly⁹-Pro¹⁰ has a modulation effect on the expression and activation of the BDNF/TrkB system in the hippocampus area. The BDNF/TrkB pathway system is a potential therapeutic target toward NPSCs proliferation after TBI. Thirty male Sprague-Dawley rats were divided into three groups, i.e A=sham-operated controls; B=TBI; C=TBI+intranasal ACTH_4-10Pro⁸-Gly⁹-Pro¹⁰ administration. After 24 h, rats' brains were immunohistochemically processed, to observe the number of cells expressing mBDNF, TrkB, and SOX2 in the subgranular zone(SGZ) of the hippocampus dentate gyrus(DG). Data were analyzed with SPSS 17, ANOVA, Post Hoc Tukey HSD test, with p value < 0,05. Mean expression of BDNF group C=16.33 ± 2.83 increased significantly compared to group A=8.33 ± 1.32(p=0.0001) and group B=5.89 ±1.69(p=0.0001). Mean expression of TrkB group C=17.00 ± 1.58 increased significantly compared to group A=4.33 ± 1.73(p=0.0001) and group B=5.89 ± 2.47(p=0.0001), TrkB expression in group B increased insignificantly compared to group A (p= 0.234).  Mean expression of SOX2 in group C=12.56 ± 2.07 increased significantly compared to group B = 8.89 ±2.318(p=0.0001) and group A=4.89 ± 2.42(p=0.0001). ACTH_4-10Pro⁸-Gly⁹-Pro¹⁰ can increase the expression of BDNF and TrkB, and the proliferation of NPSCs in the subgranular zone (SGZ) of the hippocampus dentate gyrus (DG).

Keywords: ACTH; BDNF; neural stem cells; SOX2; TrkB; SEMAX^Ò; traumatic brain injury

ABSTRAK

Kecederaan trauma otak (TBI) adalah masalah kesihatan utama di seluruh dunia kerana kadar motaliti yang tinggi dan kecacatan jangka panjang. Neural progenitor/sel stem (NPSCs) yang bertahan pada bahagian tertentu otak, membolehkan otak menghasilkan sel neuron dan glia baru. ACTH_4-10Pro⁸-Gly⁹-Pro¹⁰ mempunyai kesan modulasi pada ekspresi dan pengaktifan sistem BDNF/TrkB di kawasan hipokampus. Sistem BDNF/TrkB merupakan sasaran terapeutik yang berpotensi ke arah proliferasi NPSC selepas TBI. Tiga puluh tikus Sprague-Dawley jantan dibahagikan kepada tiga kumpulan, iaitu A=kawalan negatif; B=TBI; C=TBI+ACTH_4-10Pro⁸-Gly⁹-Pro¹⁰ intranasal. Selepas 24 jam, otak tikus diproses secara imunohistokimia untuk melihat bilangan sel yang mengekspresikan mBDNF, TrkB, dan SOX2 pada subgranular zone(SGZ) daripada hipokampus dentat girus (DG). Data dianalisis dengan ujian SPSS 17, ANOVA, Post Hoc Tukey HSD, dengan nilai p <0.05. Ekspresi BDNF kumpulan C=16.33±2.83 meningkat secara signifikan berbanding kumpulan A=8.33±1.32(p=0.0001), dan kumpulan B=5.89 ±1.69(p=0.0001). Secara keseluruhan ekspresi TrkB kumpulan C =17.00 ±1.58 meningkat secara signifikan berbanding kumpulan A=4.33±1.73(p=0.0001) dan kumpulan B=5.89±2.47(p=0.0001), ekspresi TrkB pada kumpulan B meningkat tidak signifikan dibandingkan dengan kumpulan A (p= 0.234). Rata-rata ekspresi SOX2 kumpulan C=12.56±2.07 meningkat secara signifikan dibandingkan dengan kumpulan B=8.89±2.318(p=0.0001) dan kumpulan A=4.89±2.42(p=0.0001). ACTH_4-10Pro⁸-Gly⁹-Pro¹⁰ dapat meningkatkan ekspresi BDNF dan TrkB serta meningkatkan proliferasi NPSCs pada zon subgranulr (SGZ) daripada hipokampus dentat girus (DG).

Kata kunci: ACTH; BDNF; kecederaan trauma otak; sel stem neural; SEMAX^Ò; SOX2; TrkB

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*Corresponding author; email: dr.michael.lumintang@gmail.com