Effect of intranasal stem cell administration on the nigrostriatal system in a mouse model of Parkinson's disease

Salama, Mohamed and Sobh, Mahmoud and Emam, Mahmoud and Abdalla, Ahmed and Sabry, Dina and El Gamal, Mohamed and Lotfy, Ahmed and El Husseiny, Mahmoud and Sobh, Mohamed and Sahalash, Ali and Mohamed, Wael Mohamed Yousef (2017) Effect of intranasal stem cell administration on the nigrostriatal system in a mouse model of Parkinson's disease. Experimental and Therapeutic Medicine, 13 (3). pp. 976-982. ISSN 1792-0981 E-ISSN 1792-1015

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Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. It affects the locomotor system, leading to a final severe disability through degeneration of dopaminergic neurons. Despite several therapeutic approaches used, no treatment has been proven to be effective; however, cell therapy may be a promising therapeutic method. In addition, the use of the intranasal (IN) route has been advocated for delivering various therapies to the brain. In the present study, the IN route was used for administration of mesenchymal stem cells (MSCs) in a mouse model of PD, with the aim to evaluate IN delivery as an alternative route for cell based therapy administration in PD. The PD model was developed in C57BL/6 mice using intraperitoneal rotenone administration for 60 consecutive days. MSCs were isolated from the mononuclear cell fraction of pooled bone marrow from C57BL/6 mice and incubated with micrometer‑sized iron oxide (MPIO) particles. For IN administration, we used a 20 µl of 5x105 cell suspension. Neurobehavioral assessment of the mice was performed, and after sacrifice, brain sections were stained with Prussian blue to detect the MPIO‑labeled MSCs. In addition, immunohistochemical evaluation was conducted to detect tyrosine hydroxylase (TH) antibodies in the corpus striatum and dopaminergic neurons in the substantia nigra pars compacta (SNpc). The neurobehavioral assessment revealed progressive deterioration in the locomotor functions of the rotenone group, which was improved following MSC administration. Histopathological evaluation of brain sections in the rotenone+MSC group revealed successful delivery of MSCs, evidenced by positive Prussian blue staining. Furthermore, rotenone treatment led to significant decrease in dopaminergic neuron number in SNpc, as well as similar decrease in the corpus striatum fiber density. By contrast, in animals receiving IN administration of MSCs, the degeneration caused by rotenone treatment was significantly counteracted. In conclusion, the present study validated that IN delivery of MSCs may be a potential safe, easy and cheap alternative route for stem cell treatment in neurodegenerative disorders

Item Type:	Article (Journal)
Additional Information:	7497/55873
Uncontrolled Keywords:	intranasal, stem cells, Parkinson's disease, animal model
Subjects:	R Medicine > RC Internal medicine
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Medicine > Department of Basic Medical
Depositing User:	Dr Wael Mohamed
Date Deposited:	13 Apr 2017 12:22
Last Modified:	19 Apr 2018 16:37
URI:	http://irep.iium.edu.my/id/eprint/55873

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