Docosahexaenoic acid (DHA) enhances the therapeutic potential of neonatal neural stem cell transplantation post-Traumatic brain injury

被引：23

作者：

Ghazale, Hussein ^{[1
]}

Ramadan, Naify ^{[1
]}

Mantash, Sara ^{[1
]}

Zibara, Kazem ^{[2
,3
]}

El-Sitt, Sally ^{[1
]}

Darwish, Hala ^{[1
]}

Chamaa, Farah ^{[4
]}

Boustany, Rose Mary ^{[1
,6
,7
,8
]}

Mondello, Stefania ^{[9
]}

Abou-Kheir, Wassim ^{[4
]}

Soueid, Jihane ^{[1
]}

Kobeissy, Firas ^{[1
,5
]}

机构：

[1] Amer Univ Beirut, Fac Med, Dept Biochem & Mol Genet, Beirut, Lebanon

[2] Lebanese Univ, DSST, Lab Stem Cells, ER045, Beirut, Lebanon

[3] Lebanese Univ, Fac Sci 1, Dept Biol, Beirut, Lebanon

[4] Amer Univ Beirut, Fac Med, Dept Anat Cell Biol & Physiol Sci, Beirut, Lebanon

[5] Univ Florida, Ctr Neuroprote & Biomarkers Res, Dept Psychiat, Gainesville, FL USA

[6] Amer Univ Beirut Med Ctr, Special Kids Clin, Neurogenet Program, Beirut, Lebanon

[7] Amer Univ Beirut Med Ctr, Special Kids Clin, Div Pediat Neurol, Dept Pediat, Beirut, Lebanon

[8] Amer Univ Beirut Med Ctr, Special Kids Clin, Div Pediat Neurol, Dept Adolescent Med, Beirut, Lebanon

[9] Univ Messina, AOU Policlin G Martino, Dept Biomed & Dent Sci & Morphofunct Imaging, Via Consolare Valeria, I-98125 Messina, Italy

来源：

BEHAVIOURAL BRAIN RESEARCH | 2018年 / 340卷

关键词：

Traumatic brain injury; Neural stem cells; Docosahexaenoic acid; Neurogenesis; Reactive ghosts; Motor function; CENTRAL-NERVOUS-SYSTEM; CONTROLLED CORTICAL IMPACT; STEM/PROGENITOR CELLS; NEURONAL DIFFERENTIATION; IN-VITRO; PROGENITOR CELLS; MOUSE MODEL; AGED RATS; HIPPOCAMPAL NEUROGENESIS; BREAKDOWN PRODUCTS;

D O I：

10.1016/j.bbr.2017.11.007

中图分类号：

B84 [心理学]; C [社会科学总论]; Q98 [人类学];

学科分类号：

03 ; 0303 ; 030303 ; 04 ; 0402 ;

摘要：

Traumatic Brain Injury (TBI) is a major cause of death and disability worldwide with 1.5 million people inflicted yearly. Several neurotherapeutic interventions have been proposed including drug administration as well as cellular therapy involving neural stem cells (NSCs). Among the proposed drugs is docosahexaenoic acid (DHA), a polyunsaturated fatty acid, exhibiting neuroprotective properties. In this study, we utilized an innovative intervention of neonatal NSCs transplantation in combination with DHA injections in order to ameliorate brain damage and promote functional recovery in an experimental model of TBI. Thus, NSCs derived from the sub ventricular zone of neonatal pups were cultured into neurospheres and transplanted in the cortex of an experimentally controlled cortical impact mouse model of TBI. The effect of NSC transplantation was assessed alone and/or in combination with DHA administration. Motor deficits were evaluated using pole climbing and rotarod tests. Using immunohistochemistry, the effect of transplanted NSCs and DHA treatment was used to assess astrocytic (Glial fibrillary acidic protein, GFAP) and microglial (ionized calcium binding adaptor molecule-1, IBA-1) activity. In addition, we quantified neuroblasts (doublecortin; DCX) and dopaminergic neurons (tyrosine hydroxylase; TH) expression levels. Combined NSC transplantation and DHA injections significantly attenuated TBI-induced motor function deficits (pole climbing test), promoted neurogenesis, coupled with an increase in glial reactivity at the cortical site of injury. In addition, the number of tyrosine hydroxylase positive neurons was found to increase markedly in the ventral tegmental area and substantia nigra in the combination therapy group. Immunoblotting analysis indicated that DHA + NSCs treated animals showed decreased levels of 38 kDa GFAP-BDP (breakdown product) and 145 kDa all-spectrin SBDP indicative of attenuated calpain/caspase activation. These data demonstrate that prior treatment with DHA may be a desirable strategy to improve the therapeutic efficacy of NSC transplantation in TBI.

引用

页码：1 / 13

页数：13